Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Receptors, Dopamine: Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.Corpus Luteum: The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE.Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure.Substantia Nigra: The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Agenesis of Corpus Callosum: Birth defect that results in a partial or complete absence of the CORPUS CALLOSUM. It may be isolated or a part of a syndrome (e.g., AICARDI'S SYNDROME; ACROCALLOSAL SYNDROME; ANDERMANN SYNDROME; and HOLOPROSENCEPHALY). Clinical manifestations include neuromotor skill impairment and INTELLECTUAL DISABILITY of variable severity.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neostriatum: The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.Corpora Allata: Paired or fused ganglion-like bodies in the head of insects. The bodies secrete hormones important in the regulation of metamorphosis and the development of some adult tissues.Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres.Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra.Corpus Luteum Maintenance: Process of maintaining the functions of CORPORA LUTEA, specifically PROGESTERONE production which is regulated primarily by pituitary LUTEINIZING HORMONE in cycling females, and by PLACENTAL HORMONES in pregnant females. The ability to maintain luteal functions is important in PREGNANCY MAINTENANCE.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Luteolysis: Degradation of CORPUS LUTEUM. In the absence of pregnancy and diminishing trophic hormones, the corpus luteum undergoes luteolysis which is characterized by the involution and cessation of its endocrine function.Putamen: The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system.Cellular Phone: Analog or digital communications device in which the user has a wireless connection from a telephone to a nearby transmitter. It is termed cellular because the service area is divided into multiple "cells." As the user moves from one cell area to another, the call is transferred to the local transmitter.Societies, Medical: Societies whose membership is limited to physicians.EuropeMobile Applications: Computer programs or software installed on mobile electronic devices which support a wide range of functions and uses which include television, telephone, video, music, word processing, and Internet service.Computers, Handheld: A type of MICROCOMPUTER, sometimes called a personal digital assistant, that is very small and portable and fitting in a hand. They are convenient to use in clinical and other field situations for quick data management. They usually require docking with MICROCOMPUTERS for updates.Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Lewy Body Disease: A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.Lewy Bodies: Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.Legal Guardians: A legal concept for individuals who are designated to act on behalf of persons who are considered incapable of acting in their own behalf, e.g., minors and persons found to be not mentally competent.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Dementia, Vascular: An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44)Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Telencephalon: The anterior subdivision of the embryonic PROSENCEPHALON or the corresponding part of the adult prosencephalon that includes the cerebrum and associated structures.Intercellular Adhesion Molecule-1: A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Cell Adhesion: Adherence of cells to surfaces or to other cells.Vascular Cell Adhesion Molecule-1: Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)Lymphocyte Function-Associated Antigen-1: An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.Histiocytosis, Langerhans-Cell: A group of disorders resulting from the abnormal proliferation of and tissue infiltration by LANGERHANS CELLS which can be detected by their characteristic Birbeck granules (X bodies), or by monoclonal antibody staining for their surface CD1 ANTIGENS. Langerhans-cell granulomatosis can involve a single organ, or can be a systemic disorder.Salivary Glands, Minor: Accessory salivary glands located in the lip, cheek, tongue, floor of mouth, palate and intramaxillary.Langerhans Cells: Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.Salivary Glands: Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND).Salivary Gland Neoplasms: Tumors or cancer of the SALIVARY GLANDS.Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Genitalis: Infection of the genitals (GENITALIA) with HERPES SIMPLEX VIRUS in either the males or the females.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Herpes Simplex: A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)Herpesvirus 2, Human: A species of SIMPLEXVIRUS associated with genital infections (HERPES GENITALIS). It is transmitted by sexual intercourse and close personal contact.Herpes Labialis: Herpes simplex, caused by type 1 virus, primarily spread by oral secretions and usually occurring as a concomitant of fever. It may also develop in the absence of fever or prior illness. It commonly involves the facial region, especially the lips and the nares. (Dorland, 27th ed.)Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.

Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. (1/4611)

In order to identify molecular mechanisms involved in striatal development, we employed a subtraction cloning strategy to enrich for genes expressed in the lateral versus the medial ganglionic eminence. Using this approach, the homeobox gene Meis2 was found highly expressed in the lateral ganglionic eminence and developing striatum. Since Meis2 has recently been shown to be upregulated by retinoic acid in P19 EC cells (Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Sapin, V., Chambon, P. and Dolle, P. (1997) Dev. Dyn. 210, 173-183), we examined a potential role for retinoids in striatal development. Our results demonstrate that the lateral ganglionic eminence, unlike its medial counterpart or the adjacent cerebral cortex, is a localized source of retinoids. Interestingly, glia (likely radial glia) in the lateral ganglionic eminence appear to be a major source of retinoids. Thus, as lateral ganglionic eminence cells migrate along radial glial fibers into the developing striatum, retinoids from these glial cells could exert an effect on striatal neuron differentiation. Indeed, the treatment of lateral ganglionic eminence cells with retinoic acid or agonists for the retinoic acid receptors or retinoid X receptors, specifically enhances their striatal neuron characteristics. These findings, therefore, strongly support the notion that local retinoid signalling within the lateral ganglionic eminence regulates striatal neuron differentiation.  (+info)

Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. (2/4611)

Nigrostriatal dopaminergic neurons undergo sprouting around the margins of a striatal wound. The mechanism of this periwound sprouting has been unclear. In this study, we have examined the role played by the macrophage and microglial response that follows striatal injury. Macrophages and activated microglia quickly accumulate after injury and reach their greatest numbers in the first week. Subsequently, the number of both cell types declines rapidly in the first month and thereafter more slowly. Macrophage numbers eventually cease to decline, and a sizable group of these cells remains at the wound site and forms a long-term, highly activated resident population. This population of macrophages expresses increasing amounts of glial cell line-derived neurotrophic factor mRNA with time. Brain-derived neurotrophic factor mRNA is also expressed in and around the wound site. Production of this factor is by both activated microglia and, to a lesser extent, macrophages. The production of these potent dopaminergic neurotrophic factors occurs in a similar spatial distribution to sprouting dopaminergic fibers. Moreover, dopamine transporter-positive dopaminergic neurites can be seen growing toward and embracing hemosiderin-filled wound macrophages. The dopaminergic sprouting that accompanies striatal injury thus appears to result from neurotrophic factor secretion by activated macrophages and microglia at the wound site.  (+info)

N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia. (3/4611)

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 micromol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.  (+info)

Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis. (4/4611)

Subacute and long-term stability of measurements of D2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [11C]-Raclopride and the transient equilibrium method were used to measure D2 receptor characteristics. The interval between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest analysis of quantitative measurements of D2 receptor Bmax and Kd was compared with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in the parameter estimation procedure was explored with simulations. The subacute test-retest indicates good reproducibility of D2 receptor density, affinity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements after 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute variability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulations indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good overall stability of the equilibrium method with [11C]raclopride for measuring dopamine D2 receptor binding characteristics in the striatum. The BP approach is more stable than Kd and especially Bmax measurements. Error in defining the tmax in particular in the low specific radioactivity scan may be one source of greater variability in Bmax versus BP. However, a higher intraindividual variability in measurements of the D2 receptor Bmax also may include a component of continuous regulation of this parameter over time. These methodologic aspects should be considered in the design and interpretation of longitudinal studies on D2 dopamine receptor characteristics with [11C]-raclopride.  (+info)

Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size. (5/4611)

The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.  (+info)

(S)-(-)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner. (6/4611)

Cotinine, a major peripheral metabolite of nicotine, has recently been shown to be the most abundant metabolite in rat brain after peripheral nicotine administration. However, little attention has been focused on the contribution of cotinine to the pharmacological effects of nicotine exposure in either animals or humans. The present study determined the concentration-response relationship for (S)-(-)-cotinine-evoked 3H overflow from superfused rat striatal slices preloaded with [3H]dopamine ([3H]DA) and whether this response was mediated by nicotinic receptor stimulation. (S)-(-)-Cotinine (1 microM to 3 mM) evoked 3H overflow from [3H]DA-preloaded rat striatal slices in a concentration-dependent manner with an EC50 value of 30 microM, indicating a lower potency than either (S)-(-)-nicotine or the active nicotine metabolite, (S)-(-)-nornicotine. As reported for (S)-(-)-nicotine and (S)-(-)-nornicotine, desensitization to the effect of (S)-(-)-cotinine was observed. The classic nicotinic receptor antagonists mecamylamine and dihydro-beta-erythroidine inhibited the response to (S)-(-)-cotinine (1-100 microM). Additionally, 3H overflow evoked by (S)-(-)-cotinine (10-1000 microM) was inhibited by superfusion with a low calcium buffer. Interestingly, over the same concentration range, (S)-(-)-cotinine did not inhibit [3H]DA uptake into striatal synaptosomes. These results demonstrate that (S)-(-)-cotinine, a constituent of tobacco products and the major metabolite of nicotine, stimulates nicotinic receptors to evoke the release of DA in a calcium-dependent manner from superfused rat striatal slices. Thus, (S)-(-)-cotinine likely contributes to the neuropharmacological effects of nicotine and tobacco use.  (+info)

Ergoline derivative LEK-8829-induced turning behavior in rats with unilateral striatal ibotenic acid lesions: interaction with bromocriptine. (7/4611)

LEK-8829 [9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8- aminomethylergoline bimaleinate] is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in intact animals and a D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilateral striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK-8829 in a model with innervated dopamine receptors. The IA-lesioned rats circled ipsilaterally when challenged with apomorphine, the mixed agonist on D1/D2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D1 receptor antagonist SCH-23390. The treatment with D1 receptor agonist SKF-82958 induced ipsilateral turning, whereas the treatment with D2 receptor antagonist haloperidol induced contralateral posture. The combined treatment with SKF-82958 and haloperidol resulted in a weak contralateral turning, indicating the possible receptor mechanism of contralateral turning induced by LEK-8829. Bromocriptine induced a weak ipsilateral turning that was blocked by haloperidol. The ipsilateral turning induced by bromocriptine was significantly potentiated by the coadministration of a low dose but not by a high dose of LEK-8829. The potentiation of turning was blocked either by SCH-23390 or by haloperidol. The potentiation of ipsilateral turning suggests the costimulation of D2 and D1 receptors by bromocriptine and LEK-8829, respectively, whereas the lack of potentiation by the highest dose of LEK-8829 may be explained by the opposing activity of LEK-8829 and bromocriptine at D2 receptors. We propose that the D2 and 5HT2 receptor-blocking and D1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia.  (+info)

Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons. (8/4611)

The 5-HT1A and 5-HT1B serotonin receptors are expressed in a variety of neurons in the central nervous system. While the 5-HT1A receptor is found on somas and dendrites, the 5-HT1B receptor has been suggested to be localized predominantly on axon terminals. To study the intracellular addressing of these receptors, we have used in vitro systems including Madin-Darby canine kidney (MDCK II) epithelial cells and primary neuronal cultures. Furthermore, we have extended these studies to examine addressing in vivo in transgenic mice. In epithelial cells, 5-HT1A receptors are found on both apical and basolateral membranes while 5-HT1B receptors are found exclusively in intracellular vesicles. In hippocampal neuronal cultures, 5-HT1A receptors are expressed on somatodendritic membranes but are absent from axons. In contrast, 5-HT1B receptors are found on both dendritic and axonal membranes, including growth cones where they accumulate. Using 5-HT1A and 5-HT1B knockout mice and the binary tTA/tetO system, we generated mice expressing these receptors in striatal neurons. These in vivo experiments demonstrate that, in striatal medium spiny neurons, the 5-HT1A receptor is restricted to the somatodendritic level, while 5-HT1B receptors are shipped exclusively toward axon terminals. Therefore, in all systems we have examined, there is a differential sorting of the 5-HT1A and 5-HT1B receptors. Furthermore, we conclude that our in vivo transgenic system is the only model that reconstitutes proper sorting of these receptors.  (+info)

Information processing in the striatum is critical for basal ganglia function and strongly influenced by neuromodulators (e.g., dopamine). The striatum also receives modulatory afferents from the histaminergic neurons in the hypothalamus which exhibit a distinct diurnal rhythm with high activity during wakefulness, and little or no activity during sleep. In view of the fact that the striatum also expresses a high density of histamine receptors, we hypothesized that released histamine will affect striatal function. We studied the role of histamine on striatal microcircuit function by performing whole-cell patch-clamp recordings of neurochemically identified striatal neurons combined with electrical and optogenetic stimulation of striatal afferents in mouse brain slices. Bath applied histamine had many effects on striatal microcircuits. Histamine, acting at H(2) receptors, depolarized both the direct and indirect pathway medium spiny projection neurons (MSNs). Excitatory, glutamatergic input to both
We compared for the first time the effects of de novo versus long-term l-Dopa treatment inducing abnormal involuntary movement on striatal gene profiles and related bio-associations in the 6-hydroxydopamine rat model of Parkinsons disease. We examined the pattern of striatal messenger RNA expression over 4854 genes in hemiparkinsonian rats treated acutely or chronically with l-Dopa, and subsequently verified some of the gene alterations by in situ hybridization or real-time quantitative PCR. We found that de novo and long-term l-Dopa share common gene regulation features involving phosphorylation, signal transduction, secretion, transcription, translation, homeostasis, exocytosis and synaptic transmission processes. We also found that the transcriptomic response is enhanced by long-term l-Dopa and that specific biological alterations are underlying abnormal motor behavior. Processes such as growth, synaptogenesis, neurogenesis and cell proliferation may be particularly relevant to the long-term action
Marinković, R.; Polzović, A.; Gudović, R.; Mijatov-Ukropina, L.; Marjanović, M., 1987: Stereologic analysis of the development of the corpus striatum between the 14th and 19th week of gestational age
In sum, we have been able to attenuate the function of CREB family transcription factors in dorsal striatum through expression of a dominant-negative CREB mutant, KCREB. These animals have a specific deficit in distinct forms of striatum-dependent procedural learning, without showing deficits in either motor learning on the rotarod or in spatial learning in the Morris water maze (data not shown). Furthermore, the mutant animals show a marked deficit in both LTP and LTD at the glutamatergic corticostriatal projection.. Whereas the role of the dorsal striatum in cognitive processes is increasingly appreciated, the cellular and molecular mechanisms of striatum-dependent procedural learning are poorly understood. Although corticostriatal synaptic plasticity has been extensively investigated, its relationship to striatum-dependent procedural learning remains unclear.. One obstacle to clarifying this relationship has been the difficulty of identifying clearly dorsal striatum-dependent learning tasks. ...
Foetal brain tissue. Coloured scanning electron micrograph (SEM) of a section through the corpus striatum of a foetal brain. The corpus striatum is filled with neurons (nerve cells), which are responsible for passing information around the central nervous system (CNS). Each neuron consists of a cell body (round) surrounded by many extensions called dendrites. Dendrites collect information from other neurons or from sensory cells. Each neuron also has one process called an axon, which passes information to other neurons. The corpus striatum, which forms part of the basal ganglia deep in the cerebral hemispheres, is involved in the control of posture and movement. - Stock Image P360/0466
Basal Ganglia are evolutionarily conserved brain nuclei involved in several physiologically important animal behaviors like motor control and reward learning. Striatum, which is the input nuclei of basal ganglia, integrates inputs from several neurons, like cortical and thalamic glutamatergic input and local GABAergic inputs. Several neuromodulators, such as dopamine, accetylcholine and serotonin modulate the functional properties of striatal neurons. Aberrations in the intracellular signaling of these neurons lead to several debilitating neurodegenerative diseases, like Parkinsons disease. In order to understand these aberrations we should first identify the role of different molecular players in the normal physiology.. The long term goal of this research is to understand the molecular mechanisms responsible for the integration of different neuromodulatory signals by striatal medium spiny neurons (MSN). This signal integration is known to play important role in learning. This is manifested via ...
Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinsons disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinsons disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation ...
There were two sets of experiments. The first set placed bi-directional tracers into different regions of the striatum (see Fig.1 a). These cases were analyzed first for the distribution of labeled cells in the frontal cortex. On the basis of the cortical labeling pattern, each injection site was classified as follows. (1) "Motor" striatum were injection sites that labeled cells primarily in frontal cortical areas 4 and 6 with few labeled cells in areas 9 and 46, and scattered cells, or none, in orbitofrontal regions or in areas 32, 25, 24, a or b; (2) "limbic" striatum were injection sites that labeled cells primarily in areas 32, 25, 24, a and b, and medial orbitofrontal cortex, areas 10, 14, and 13, with few labeled cells in areas 9 and 46 and none in areas 4 and 6. We defined the shell as the ventral striatal region that was calbindin (CaBP) negative and the rest of the ventromedial striatum as the "core" (Meredith et al., 1996). (3) Association areas comprised injection sites that labeled ...
TY - JOUR. T1 - The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation. AU - Mowery, Todd M.. AU - Penikis, Kristina B.. AU - Young, Stephen K.. AU - Ferrer, Christopher E.. AU - Kotak, Vibhakar C.. AU - Sanes, Dan. PY - 2017/6/20. Y1 - 2017/6/20. N2 - Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL), are commonly linked with processing deficits at or below the level of the auditory cortex (ACx). However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, ...
Author Summary Recent brain imaging and neurophysiological studies suggest that the striatum, the start of the basal ganglia circuit, plays a major role in value-based decision making and behavioral disorders such as drug addiction. The plasticity of synaptic input from the cerebral cortex to output neurons of the striatum, which are medium spiny neurons, depends on interactions between glutamate input from the cortex and dopaminergic input from the midbrain. It also links sensory and cognitive states in the cortex with reward-oriented action outputs. The mechanisms involved in molecular cascades that transmit glutamate and dopamine inputs to changes in postsynaptic glutamate receptors are very complex and it is difficult to intuitively understand the mechanism. Therefore, a biochemical network model was constructed, and computer simulations were performed. The model reproduced dopamine-dependent and calcium-dependent forms of long-term depression (LTD) and potentiation (LTP) of corticostriatal synapses
Foetal brain cells. Coloured scanning electron micrograph (SEM) of neurons (nerve cells) in the corpus striatum of a foetal brain. Neurons are responsible for passing information around the central nervous system (CNS). Each neuron consists of a cell body (red) surrounded by many extensions called dendrites. Dendrites collect information from other neurons or from sensory cells. Each neuron also has one process called an axon, which passes information to other neurons. The corpus striatum, which forms part of the basal ganglia deep in the cerebral hemispheres, is involved in the control of posture and movement. - Stock Image P360/0464
Results: As consequence of AAV-mediated A53T overexpression, significant decrease of [18F]FMT accumulation was recorded in the striatum ipsilateral to the lesion. Lesioned rats had dramatically reduced uptake constant Ki in the ipsilateral striatum compared to the contralateral striatum (p,0.001 for [18F]FMT) and to the ipsilateral striatum of sham-treated rats (p,0.001). Significant deficit in stepping adjustment was observed with the contralateral forepaw at 4, 12 and 18 weeks. Significant reduction of the time spent on the rotarod was also measured at 12 and 18 weeks ...
The thrust of this paper is that the noncoding RNA BC1 is responsible for regulating D2-mediated synaptic transmission. Perhaps the greatest strength of the study is the robust neurophysiology and pharmacology with tight controls. That data set shows, using corticostriatal slice preparations, that the dopaminergic perturbation (hypersensitivity) is specific for the D2 receptor in BC1-knockout mice. This is especially important in light of the "anxiety" phenotype these mice express, and the probable role(s) of striatal dopamine in human psychiatric diseases. The authors then show that BC1 is apparently present in axons and in striatal GABAergic cells.. A challenge for this work is that the actual mechanism by which BC1 works is as yet poorly understood. That BC1 may be present in axons has been shown previously; however, the significance of axonal BC1 remains obscure. The authors show that D2DR mRNA and protein levels are not dramatically decreased (protein appears increased) in the BC1 KO mice, ...
We present a network model of striatum, which generates winnerless dynamics typical for a network of sparse, unidirectionally connected inhibitory units. We observe that these dynamics, while interesting and a good match to normal striatal electrophysiological recordings, are fragile. Specifically …
The unexpected finding that neurons can co-release two neurotransmitter molecules, dopamine and GABA, through a common mechanism provides a further advance in our understanding of the nervous system. See Letter p.262 The striatum sits at a crossroads for a variety of brain inputs, including those from the cortex, hippocampus and midbrain. Large populations of dopaminergic neurons in the basal ganglia project to the striatum; recent genetic tools have made it possible to isolate these neurons and control them with light exposure using optogenetic techniques. Here, Bernardo Sabatini and colleagues report an unexpected function for these dopaminergic neurons in inhibiting striatal output. They find that the fast-acting neurotransmitter GABA is the source of this inhibition. Interestingly, GABA was not loaded into vesicles through the usual route, but through the VMAT2 transporter that also transfers dopamine. These findings extend the dynamics of dopaminergic neuron signalling and represent an example of
Grades 3 & up. Students can look inside their own heads with this realistic model. Plastic model includes a stand and guide with facts and photo-illustrated assembly instructions. Features cerebellum, frontal, parietal, temporal and occipital lobes; corpus callosum, brain stem, hippocampus, ventricles, insula, corpus striatum, internal capsule and lentiform nucleus. Perfect in a nervous system center for a deeper understanding of how the parts of the brain work together. 31-piece model measures… More » ...
1 . Damodaran S, Cressman JR, Jedrzejewski-Szmek Z, Blackwell KT (2015) Desynchronization of Fast-Spiking Interneurons Reduces beta-Band Oscillations and Imbalance in Firing in the Dopamine-Depleted Striatum. J Neurosci 35:1149-59 [PubMed] ...
1 . Damodaran S, Cressman JR, Jedrzejewski-Szmek Z, Blackwell KT (2015) Desynchronization of fast-spiking interneurons reduces ß-band oscillations and imbalance in firing in the dopamine-depleted striatum. J Neurosci 35:1149-59 [PubMed] ...
The neurotoxic consequences of opiate drug and HIV-1 interactions on striatal neurons and on the underlying intracellular signaling pathways (autophagy, ER-stre...
Glutamic Acid;Central Nervous System;Neurons;Neurotransmitter Agents;Carrier Proteins;Corpus Striatum;Cyclic AMP-Dependent Protein Kinases;Dopamine;Excitatory Amino Acids;Receptors, Metabotropic Glutamate;Synaptic Transmission;Rats, Sprague- ...
TY - JOUR. T1 - The effect of ASIC3 knockout on corticostriatal circuit and mouse self-grooming behavior. AU - Wu, Wei-Li. AU - Cheng, Sin Jhong. AU - Lin, Shing Hong. AU - Chuang, Yu Chia. AU - Huang, Eagle Yi Kung. AU - Chen, Chih Cheng. PY - 2019/1/29. Y1 - 2019/1/29. N2 - Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. ...
BioAssay record AID 63789 submitted by ChEMBL: Evaluated for the affinity against Dopamine receptor D2 in rat striatal membranes.
The mechanism underlying a hypercholinergic state in Parkinsons disease (PD) remains uncertain. Here, we show that disruption of the K(v)1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing K(v)1.3 subunits contribute significantly to the orphan potassium current known as I-sAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by K(v)1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic ...
The chronic use of nicotine, the main psychoactive ingredient of tobacco smoking, alters diverse physiological processes and consequently generates physical dependence. To understand the impact of chronic nicotine on neuropeptides, which are potential molecules associated with dependence, we conducted qualitative and quantitative neuropeptidomics on the rat dorsal striatum, an important brain region implicated in the preoccupation/craving phase of drug dependence. We used extensive LC-FT-MS/MS analyses for neuropeptide identification and LC-FT-MS in conjunction with stable isotope addition for relative quantification. The treatment with chronic nicotine for 3 months led to moderate changes in the levels of endogenous dorsal striatum peptides. Five enkephalin opioid peptides were up-regulated, although no change was observed for dynorphin peptides. Specially, nicotine altered levels of nine non-opioid peptides derived from precursors, including somatostatin and cerebellin, which potentially ...
Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically defined models can provide an entry point to studying the molecular underpinnings of this disorder. We generated germline mutant mice with loss-of-function mutations in Chd8, a de novo mutation strongly associated with ASD, and demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and craniofacial abnormalities similar to patient phenotypes. Chd8 mice display a broad, brain-region-specific dysregulation of major regulatory and cellular processes, most notably histone and chromatin modification, mRNA and protein processing, Wnt signaling, and cell-cycle regulation. We also find altered synaptic physiology in medium spiny neurons of the nucleus accumbens. Perturbation of Chd8 in adult mice recapitulates improved acquired motor learning behavior found in Chd8 animals, suggesting a role for CHD8 in adult striatal circuits. These results support a mechanism linking chromatin modification to striatal ...
Chronic intoxication by 3-nitropropionic acid in the Lewis rat reproduces many features reminiscent of Huntingtons disease including behavioural alterations and cortico-striatal degeneration. In particular, in this model, striatal degeneration is accompanied by calpain activation as found in the human disease. The present study was undertaken to determine whether the expression of Alix (apoptosis linked gene-2 interacting protein), a widespread protein involved in neuronal death, would be modified in the striatum and cortex of 3NP-treated rats. The results clearly show that Alix immunoreactivity is increased in the neuronal cell bodies of the lateral striatum, where degeneration is massive. The medial striatum and the cortex that lack neurodegeneration remain only weakly labelled. This is further evidence suggesting an involvement of Alix in the events driving neuronal death.
Substantial evidence indicates that the dorsolateral striatum is needed to execute sensorimotor habits (Yin et al., 2004, 2006; Redgrave et al., 2010). Such behaviors are highly repetitive, are mediated by stimulus-response (S-R) associations, and are expressed even in the absence of reinforcement. In rats, focal lesions in the dorsolateral striatum disrupt the normal sequence of repetitive, stereotyped grooming behaviors [Cromwell and Berridge, 1996). Although the normal sequence of grooming behavior is clearly disrupted, the capacity to emit individual grooming movements is not affected. Consistent with this distinction, neurons in the dorsolateral striatum appear to encode the serial order of sequential grooming movements (Aldridge and Berridge, 1998). Furthermore, the striatal sites associated with stereotyped grooming behaviors are located in regions that receive corticostriatal projections from the forepaw and, to a lesser extent, the whisker representations in SI cortex (Hoover et al., ...
Intrastriatal application of the D1 antagonist SCH 23390 by two procedures, reverse dialysis (20-mu-M) and local injection (0.45 nmol per striatum), elicited a reduction in acetylcholine (ACh) release superimposable on that induced by systemic administration. The novel selective D1 antagonist SCH 39166 produced a similar decreasing effect on striatal ACh release on local injection (0.45 nmol per striatum). On the other hand, local application of SCH 23390 into the frontal cortices (0.45 nmol per side) failed to alter striatal ACh overflow, indicating that the drug does not diffuse out of its injection site to any significant extent. The dopamine release inducer d-amphetamine (2 mg/kg s.c.) and the dopamine uptake inhibitor cocaine raised ACh release like the D1 agonists. These effects were completely blocked by 10-mu-M SCH 23390 applied by reverse dialysis. The results suggest that D1 receptors regulating ACh release are located in the striatum.. ...
The role of dopamine in plasticity at glutamatergic synapses in the striatum is central to our understanding of basal ganglia functions and dopamine-dependent reward mechanisms. Long-term potentiation (LTP) and long-term depression (LTD) at these synapses are thought to be dependent on D1 and D2 dopamine receptors, respectively. However, the mechanisms of LTP and LTD in the striatum are controversial. Using brain slices from transgenic mice, Shen et al. show that LTP and LTD can occur in both D1- and D2-expressing neurons but with different molecular mechanisms. Dopaminergic modulation of plasticity is receptor and cell-type specific. The findings suggest that the control of bidirectional plasticity is not exerted through a monolithic mechanism, as previously asserted, but by cell-type-specific mechanisms depending on the subtype of dopamine receptor expressed.. W. Shen, M. Flajolet, P. Greengard, D. J. Surmeier, Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, ...
Suprathreshold corticostriatal responses recorded from medium spiny neurons (MSNs) from the direct and indirect pathways of the basal ganglia are different. Their differences readily distinguish D1- and D2-type receptor expressing MSNs in both bacterial artificial chromosome-transgenic mice and their control littermates as well as in rats: indirect pathway neurons are more excitable than direct pathway neurons revealing autoregenerative spikes underlying their spike trains, whereas direct pathway neurons exhibit more prolonged plateau potentials and spike trains. SFK 81297, a selective agonist for D1-class receptors enhanced corticostriatal responses in direct pathway neurons, while quinelorane, a selective agonist for D2-class receptors reduced orthodromic and autoregenerative responses in indirect pathway neurons thus making both neuron classes similarly excitable. Because dopaminergic postsynaptic actions target CaV1 (L) class voltage-gated calcium channels in MSNs, we hypothesized that these
Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. Recently, it was reported that one popular line of these mice--mice possessing a BAC transgene with a D(2) dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter--had abnormal striatal gene expression, physiology, and motor behavior. Unlike most of the work using BAC mice, this interesting study relied upon mice backcrossed on the outbred Swiss Webster (SW) strain that were homozygous for the Drd2-eGFP BAC transgene. The experiments reported here were conducted to determine whether mouse strain or zygosity was a factor in the reported abnormalities. As reported, SW mice were very sensitive to transgene expression. However, in more commonly used inbred strains of mice (C57BL/6, FVB/N) that were hemizygous for the transgene, the Drd2-eGFP BAC transgene did ...
Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling Journal Article ...
Using whole-cell patch-clamp recording in brain slices17-19⇓⇓ and in vivo microdialysis methods,20 the major target neurons of A2A receptor-mediated modulation were identified as GABAergic striatopallidal medium spiny neurons (MSNs).1 These striatal projection neurons may receive A2A receptor-mediated regulation in two distinct modes. The main loci of this adenosine A2A receptor-mediated dual modulation in the striatopallidal system1,21⇓ are as follows. 1) In the striatum, A2A receptors control excitability of the projection neurons through the intrastriatal GABAergic feedback and feed-forward inhibition network.17 Major elements regulating the excitability of MSNs in the striatum are GABAergic inputs, which come from axon collaterals of the MSNs themselves and GABAergic interneurons. A2A receptors on the axon terminals of these GABAergic neurons suppress GABA release, resulting in an increase in MSN excitability via relief of intrastriatal GABAergic inhibitory inputs onto the MSNs. This ...
Parkinsons disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence:
The cyclic nucleotides cAMP and cGMP are common signaling molecules synthesized in neurons following the activation of adenylyl or guanylyl cyclase. In the striatum, the synthesis and degradation of cAMP and cGMP is highly regulated as these second messengers have potent effects on the activity of striatonigral and striatopallidal neurons. This review will summarize the literature on cyclic nucleotide signaling in the striatum with a particular focus on the impact of cAMP and cGMP on the membrane excitability of striatal medium-sized spiny output neurons (MSNs). The effects of non-selective and selective phosphodiesterase (PDE) inhibitors on membrane activity and synaptic plasticity of MSNs will also be reviewed. Lastly, this review will discuss the implications of the effects PDE modulation on electrophysiological activity of striatal MSNs as it relates to the treatment of neurological disorders such as Huntingtons and Parkinsons disease.
Electrophysiological and microfluorometric measurements were combined to analyse the responses of rat striatal medium spiny (MS) and large aspiny (LA) interneurons to the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylidrazone (FCCP). FCCP produced a membrane depolarisation coupled to an irreversible increase in intracellular calcium [Ca2+]i in MS. Conversely, LA interneurons hyperpolarised and a moderate [Ca2+]i rise was observed. Cyclosporin A, inhibitor of the mitochondrial membrane transition pore, prevented the FCCP-induced changes in LA interneurons, whereas only a partial reduction was observed in MS cells. The present results indicate that mitochondrial Ca2+ released into the cytosol may contribute to the selective vulnerability to metabolic impairment in striatal neuronal subtypes.. ...
The strength and specificity with which a neuron forms synapses is a fundamental question in evaluating its function. To address this for striatal medium spiny neurons (MSNs), Chuhma et al used an optogenetic approach reminiscent of the aforementioned Bardi et al study. First, they bred a mouse that selectively expressed ChR2 in striatal MSNs. Then, they recorded (in…
Previous work showed differences in the polysynaptic activation of GABAergic synapses during corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (dSPNs and iSPNs). Here, we now show differences and similarities in the polysynaptic activation of cortical glutamatergic synapses on the same responses. Corticostriatal contacts have been extensively studied. However, several questions remain unanswered, e.g.: what are the differences and similarities in the responses to glutamate in dSPNs and iSPNs? Does glutamatergic synaptic activation exhibits a distribution of latencies over time in vitro? That would be a strong suggestion of polysynaptic cortical convergence. What is the role of kainate receptors in corticostriatal transmission? Current-clamp recordings were used to answer these questions. One hypothesis was: if prolonged synaptic activation distributed along time was present, then it would be mainly generated from the cortex, and not from the striatum. ...
The function of striatopallidal neurons is regulated by N-methyl-d-aspartate (NMDA) and dopamine D2 receptors. Previous studies show that immediate early gene induction by D2 receptor blockade is suppressed by NMDA receptor antagonists. Because the pharmacology of NMDA receptors depends on the incorporation of different NR2 subunits and NR2 subunits show regional and cellular differences in their expression in striatum, our study examined whether different NMDA receptor antagonists would have differential effects on eticlopride-induced immediate early gene expression in striatum. Male Sprague-Dawley rats were pretreated with vehicle, CGS 19755, MK-801 or ifenprodil. Rats then received injections of eticlopride and were killed 40 min later. In situ hybridization histochemistry was used to determine the expression of c-fos andzif268 in the striatum. Eticlopride increased immediate early gene expression in striatum, with the increase generally being greater in lateral than in medial striatum. ...
Stress induces a shift from hippocampus-dependent "cognitive" toward dorsal striatum-dependent "habit" memory. However, not all individuals are susceptible to this shift under stress. Based on pharmacological studies indicating a critical role of the mineralocorticoid receptor (MR) in the stress-induced bias toward dorsal striatal learning, we hypothesized that MR gene variants contribute to these individual differences. In two experiments, healthy participants were genotyped, exposed to a stressor or control manipulation and performed a learning task that can be solved using hippocampal or dorsal striatal systems, while electroencephalography (EEG; Experiment I) or functional magnetic resonance imaging (fMRI; Experiment II) measurements were taken ...
The effects of sodium nitroprusside (SNP), 3-morfolinosydnonimine (SIN-1), or S-nitroso-Nacetylpenicillamine (SNAP), on striatal dopamine release in freely moving rats, were evaluated using microdialysis 1 . When infused (1 mM) for 180 min, both SNP (n=3) and SIN-1 (n=3) increased DA dialysate concentrations (baseline levels 6.73±1.02 and 7.15±1.12 nM, respectively). The SNP-induced DA increase was inhibited by deferoxamine co-infusion, thus suggesting a key role for iron in SNP-induced increases in DA release. SNAP 1 mM 180 min infusion decreased dialysate DA (baseline levels 5.34±0.80 nM, n=3). The decrease was a consequence of SNAP-induced non-enzymatic oxidation of extracellular DA; in fact, the decrease was inhibited by N-acetyl-cysteine or uric acid co-infusion. Both SNP and SNAP greatly decreased dialysate ascorbic acid (AA, baseline values 10.82±2.5 and 8.55±2.62 μM, respectively); on the contrary, SIN-1 did not affect dialysate AA (baseline levels 7.90±0.73 μM). These finding ...
Defects in gene transcription and mitochondrial function have been implicated in the dominant disease process that leads to the loss of striatal neurons in Huntingtons disease (HD). Here we have used precise genetic HD mouse and striatal cell models to investigate the hypothesis that decreased cAMP responsive element (CRE)-mediated gene transcription may reflect impaired energy metabolism. We found that reduced CRE-signaling in HdhQ111 striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated inclusion formation. Furthermore, cAMP levels in HdhQ111 striatum declined from an early age (10 weeks), and cAMP was significantly decreased in HD postmortem brain and lymphoblastoid cells, attesting to a chronic deficit in man. Reduced CRE-signaling in cultured STHdhQ111 striatal cells was associated with cytosolic CREB binding protein that mirrored diminished cAMP synthesis. Moreover, mutant cells exhibited mitochondrial respiratory chain impairment, ...
Since the proposal of the classical model of the BG (3), substantial efforts have been made to uncover the selective contributions of the direct and indirect pathways to behavior. However, progress has been limited by the inability to access these neuronal populations due to the fact that they are anatomically intermixed. Here we used a genetic approach to dissect the function of these pathways by conditionally deleting the key striatal phosphoprotein, DARPP-32, in striatonigral and striatopallidal pathway neurons, using the D1R and D2R promoters to drive cell type-specific Cre recombinase expression (12). DARPP-32 plays an essential role in integrating signals from a number of behaviorally important neurotransmitters and neuromodulators that target the striatum (24). Thus, a loss of this protein would be expected to result in loss of function in each neuronal population. Supporting this, we found that deletion of DARPP-32 abolishes a key functional property of MSNs, corticostriatal LTP, in ...
Another name for the primary visual cortex (Area V1), showing in cross-section alternating bands of white matter and grey matter unrelated to the striped ocular-dominance columns and orientation columns that are made visible only by special staining procedures. Often confused with the corpus striatum and the striatum. [From Latin striatus streaked, from stria a furrow or a flute of a column] ...
lenticular nucleus definition: a basal ganglion shaped like a lens and like the external reddish putamen and the internal pale yellow pallidum
article{58bdbf8b-cb0c-4890-80c3-1b810f44ac8c, abstract = {,p,The intricate balance between dopaminergic and cholinergic neurotransmission in the striatum has been thoroughly difficult to characterize. It was initially described as a seesaw with a competing function of dopamine versus acetylcholine. Recent technical advances however, have brought this view into question suggesting that the two systems work rather in concert with the cholinergic interneurons (ChIs) driving dopamine release. In this study, we have utilized two transgenic Cre-driver rat lines, a choline acetyl transferase ChAT-Cre transgenic rat and a novel double-transgenic tyrosine hydroxylase TH-Cre/ChAT-Cre rat to further elucidate the role of striatal ChIs in normal motor function and in Parkinsons disease. Here we show that selective and reversible activation of ChIs using chemogenetic (DREADD) receptors increases locomotor function in intact rats and potentiate the therapeutic effect of L-DOPA in the rats with lesions of the ...
Allegedly birds prefer to use the corpus striatum instead of the cortex. Bluntly put, that would mean that mammals think with the nose and birds think with the eyes ...
Lerchner et al write a review in Nature Neuroscience of an article by Atallah et al. in the same issue which shows clear evidence that learning a new skill and expressing it are two separate steps that can be dissociated. From the articles abstract: "It is widely accepted that the striatum of the basal ganglia is a primary substrate for the learning and performance of skills. We provide evidence that two regions of the rat striatum, ventral and dorsal, play distinct roles in instrumental conditioning (skill learning), with the ventral striatum being critical for learning and the dorsal striatum being important for performance but, notably, not for learning. This implies an actor (dorsal) versus director (ventral) division of labor, which is a new variant of the widely discussed actor-critic architecture. Our results also imply that the successful performance of a skill can ultimately result in its establishment as a habit outside the basal ganglia ...
The striatum is the largest component of the basal ganglia, and its degeneration is the cause for motor dysfunction associated with Huntingtons disease (HD), a...
Tired of trying to set your new habit, only to have it crash and fail within a few days? So was I. Luckily, theres a relatively simple science behind habit formation that will transform the way you try to stop smoking, begin exercising, or do almost anything you want.
J:176344 Ratzka A, Baron O, Grothe C, FGF-2 deficiency does not influence FGF ligand and receptor expression during development of the nigrostriatal system. PLoS One. 2011;6(8):e23564 ...
Three types of neuron with smooth (aspiny) dendrites could be distinguished in the Golgi-impregnated rat neostriatum. Examples of each type of aspiny neuron were found with local axon collaterals within the neostriatum and these were selected for gold- toning and examination in the electron microscope. One type of aspiny neuron had an elongated, usually spindle-shaped, medium-size soma with two, or rarely three, primary dendrites originating from opposite poles of the cell; one example of this type of neuron had two separate axons. The second type of aspiny neuron had a nearly round, medium-size soma with four primary dendrites that branched profusely quite close to the cell body. A third type of aspiny neuron had a very large polygonal-shaped cell body. Afferent axon terminals were found in synaptic contact with the dendrites and cell bodies of all three types of aspiny neuron. Axon collaterals of each type of neuron displayed varicosities which, when examined in the electron microscope, were ...
Wu D. C., Jackson-Lewis V., Vila M., Tieu K., Teismann P., Vadseth C., Choi D. K., Ischiropoulos H. and Przedborski S. (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J. Neurosci. 22, 1763-1771. ...
Prolyl oligopeptidase (PREP, EC 3.4.21.26) inhibitors have potential as cognition enhancers, but the mechanism of action behind the cognitive effects remains unclear. Since acetylcholine (ACh) and dopamine (DA) are known to be associated with the regulation of cognitive processes, we investigated the effects of two PREP inhibitors on the extracellular levels of ACh and DA in the rat striatum using in vivo microdialysis. KYP-2047 and JTP-4819 were administered either as a single systemic dose (50 μmol/kg∼17 mg/kg i.p.) or directly into the striatum by retrodialysis via the microdialysis probe (12.5, 37.5 or 125 μM at 1.5 μl/min for 60 min). PREP inhibitors had no significant effect on striatal DA levels after systemic administration. JTP-4819 significantly decreased ACh levels both after systemic (by ∼25%) and intrastriatal (by ∼3050%) administration. KYP-2047 decreased ACh levels only after intrastriatal administration by retrodialysis (by ∼4050%) when higher drug levels were reached, ...
Huntingtons disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.
DOPAMINE RECEPTOR AGONISTS act to stimulate dopamine receptors, and these have a major neurotransmitter role in the CNS. Dopamine is also a precursor in the formation of the catecholamine monoamine neurotransmitter noradrenaline and the hormone adrenaline. The distribution of dopamine in the brain is very non-uniform. There is some in the limbic system, and a large proportion is found in the corpus striatum - a part of the extrapyramidal motor system which is concerned with the coordination of movement. Dopamine-containing nerves are found in three main pathways in the brain. The nigrostriatal pathway contains about 75% Of the dopamine in the brain, and the cell bodies lie in the substantia nigra and the nerves terminate in the corpus striatum. The second important pathway is the mesolimbic pathway, the cell bodies of which lie in the mid-brain and project to parts of the limbic system, particularly the nucleus accumbens. The third, the tubero-infundibular system, consists of short neurons that ...
Accumulation of transition metals has been suggested to be responsible for the deteriorated nigrostriatal dopaminergic system in Parkinsons patients. In the present study, the mechanism underlying the zinc-induced neurotoxicity was investigated in the nigrostriatal dopaminergic system in vivo. Our 6-methoxy-8-paratoluene sulfonamide quinoline fluorescence study showed zinc translocation in the infused nigral cells after intranigral infusion of zinc. Furthermore, lipid peroxidation in the zinc-infused substantia nigra was consistently elevated 4 h to 7 d after the infusion. At the same time, an abrupt increase in cytosolic cytochrome c content in the infused substantia nigra was observed 4 h after zinc infusion and gradually decreased to basal levels 7 d after infusion. Both TUNEL-positive neurons and DNA fragmentation, indicatives of apoptosis, were detected in the zinc-infused substantia nigra. Furthermore, striatal dopamine content was reduced 7 d after the infusion. In attempt to prevent zinc
Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum. Blocking monocyte recruitment did not alter the volume of the ischemic lesion but gave rise to reduced astrocyte activation in SVZ and adjacent striatum, which could contribute to the improved neuroblast survival. A similar decrease of astrocyte activation was found in and around human induced pluripotent stem cell (iPSC)-derived NSPCs transplanted into striatum at one week after ...
A substance called dopamine acts as a messenger between two brain areas - the substantia nigra and the corpus striatum - to produce smooth, controlled movements. Most of the movement-related symptoms of Parkinsons disease are caused by a lack of dopamine due to the loss of dopamine-producing cells in the substantia nigra. When the amount of dopamine is too low, communication between the substantia nigra and corpus striatum becomes ineffective, and movement becomes impaired; the greater the loss of dopamine, the worse the movement-related symptoms. Other cells in the brain also degenerate to some degree and may contribute to non-movement related symptoms of Parkinsons disease ...
Interestingly, Sema3F-Nrp2 signaling also was demonstrated to regulate dendritic spine number, size and distribution in layer 5 cortical neurons and granule cells of the hippocampus in the adult animal (Tran et al., 2009, Nature). The loss of Nrp2 enhanced excitatory synaptic transmission in both cortical and hippocampal neurons. We conducted the first behavioral study of mice harboring a mutation of the Nrp2 gene, focusing on behaviors known to depend on cortical and hippocampal circuitry. Nrp2-/- mutants showed autism-associated behavior impairments in object recognition memory, no preference for social novelty, and increased grooming behavior compared to age-matched controls (Shiflett et al., 2015, Transl Psychiatry). Furthermore, our results show Nrp2-/- animals have abnormal corticostriatal circuit activity. Currently, we are investigating the role of Sema3F-Nrp2 signaling in corticostriatal circuit function, which is known to underlie goal-directed learning and behavior. Toward this end, ...
Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome.. Xu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C.. Proc Natl Acad Sci U S A 112(3):893-898, 2015.. Postmortem studies of Tourette syndrome patients has revealed a reduction in the number of specific striatal interneurons. The authors explored the hypothesis that this neuronal deficit is enough to produce the symptoms of Tourette syndrome in mice. Animals received 90-ng injections of Anti-ChAT-SAP (Cat. #IT-42) into the striatum. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that loss of the striatal interneurons is enough to produce some, but not all, of the symptoms caused by Tourette syndrome.. Role of striatal cholinergic interneurons in set-shifting in the rat.. Aoki S, Liu AW, Zucca A, Zucca S, Wickens JR.. J Neurosci 35(25):9424-9431, 2015.. The authors examined the role that ...
Dopamine and NO are physiological stimulators of synthesis of cAMP and cGMP, respectively, and NO synthase-containing interneurons in the striatum are physiologically activated by dopamine-containing neurons in the substantia nigra. This study investigated whether lesioning dopamine neurons has multiple consequences in the striatum consistent with the reported sensitization of cAMP synthesis, including alteration of the NO-cGMP pathway and phosphodiesterase-dependent metabolism of cyclic nucleotides. The substantia nigra of adult Sprague-Dawley rats was unilaterally lesioned with 6-hydroxydopamine. Two months later, we determined expression of NO synthase and evaluated cGMP and cAMP levels of intact and deafferented striatum. Moreover, we evaluated cAMP- and cGMP-phosphodiesterase activities in basal conditions and after Ca2+-calmodulin stimulation and determined the expression of the phosphodiesterase-1B isoform and the levels of phosphodiesterase-1B mRNA. Using immunocytochemistry we ...
4-5 Day inpatient study. Participant will have scanned pictures (MRI & PET scans) taken of their brain after being injected with a small amount of WIN, a radioactive substance. Participants give daily urine samples and fill out health related questionnaires. It is important to determine whether the alterations characterized within one week of last drug use persist over a longer time period. Based on results of the studies from aims 1 & 2, we will decide which of the 2 probes, WIN or FDOPA-PET is the more sensitive index of stimulant-dependency-induced changes ...
The effect of intermittent normobaric hypoxia and of biological pyrimidines (uridine and cytidine) on the specific activities of some enzymes related to cerebral energy metabolism were studied. Measurement were carried out on the following: homogenate in toto; purified mitochondrial fraction; crude synaptosomal fraction, in different areas of rat brain: cerebral cortex, hippocampus, corpus striatum, hypothalamus, cerebellum, and medulla oblongata. Intermittent normobaric hypoxia (12 hours daily for 5 days) caused modifications of the enzyme activities in the homogenate in toto (decrease of hexokinase in cerebellum; increase of pyruvate kinase in medulla oblongata), in the purified mitochondrial fraction (increase of succinate dehydrogenase in the corpus striatum) and in the crude synaptosomal fraction (decrease of cytochrome oxidase activity in cerebral cortex, hippocampus, and cerebellum; decrease of malate dehydrogenase in hippocampus and cerebellum; decrease of lactate dehydrogenase in ...
Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally. A 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life-threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum
These data highlight two essential principles that may help realize the functional potential of striatal transplants. First, it was demonstrated that distinct response deficits were alleviated only if grafted animals received extensive postoperative training. Second, comparisons of different postoperative training regimes revealed that only specific training on the impaired contralateral side conferred functional benefit. Together, these results suggest that graft maturation and integration is insufficient by itself to mediate recovery on this task unless specific, extensive training subsequently is undertaken. Furthermore, this recovery would appear to be mediated by the restoration of basal ganglia circuitry, as permitted by the striatal graft.. A comparison of animals that were either (i) initially retrained on the contralateral side or (ii) tested only on the contralateral side once they had received extensive training on the ipsilateral side highlighted the degree of training specificity ...
This study reports the long-term safety, motor, cognitive and psychiatric effects of bilateral fetal striatal allotransplants in five patients with mild to moderate HD, in comparison with a reference group of 12 patients from the same cohort who were similarly suitable for transplantation but not selected for surgery, but were followed in an identical way.. There were no significant differences in any of the measures chosen when comparing patients with transplants with this reference cohort at baseline and followed-up for up to 10 years postsurgery, using identical protocols of assessment. In small open label studies with multiple outcome measures, it is tempting to focus on apparent improvements in individual patients on particular tests. However, although such encouraging signs could be identified in the present five patients, the changes were in all cases small; similar short-term fluctuations could be identified in control patients of the reference group; and there were no statistically ...
In the developing and adult brain, neurotrophic growth factors support the growth and protec tion of dopaminergic neuronal systems. Recently, links between impaired neurotrophin support of dopamine (DA) neurons has been described in Parkinsons Disease (PD). Fibro- blast growth factor (FGF) has a unique association with DA neurons in that FGF signaling is vitally important for the development and protection of adult DA neurons. We assessed the role of substantia nigra (SN)-expressed FGFs in the nigrostriatal dopaminergic system using a transgenic mouse, th-fgfr1(tk-). In these mice, generated by expression of dominant negative FGFR1(TK-) from the tyrosine hydroxylase (TH) gene promoter, reduced FGF signaling results in smaller and less dense adult nigrostriatal DA neurons, similar to what is observed in PD. With unilateral 6-hydroxydopamine (6-OHDA) lesions, th-fgfr1(tk-) mice exhibited extensive unilateral nigrostriatal damage with robust spontaneous (non-drug induced) asymmetrical turning and a
Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies. ...
Drug addiction involves perseverant and compulsive drug seeking and attempts to obtain and consume drugs despite aversive consequences. One leading circuit-level hypothesis for how addiction arises is that maladaptive neuroadaptations are caused by reward circuits because the dopamine system is usurped by the addictive substances (Everitt and Robbins, 2005; Wise, 1998). The main brain areas composing the reward circuits are distributed across multiple areas and include the basal ganglia (including the striatum), the limbic system (including the amygdala and the hippocampus), and the prefrontal cortex (PFC). Among these regions, the striatum is the core input nucleus and plays key roles in reward-related learning as well as in addictive behaviors. The acquisition and maintenance of addiction-like behaviors appear to arise from a series of molecular and cellular adaptations in striatal circuits (Gerfen and Surmeier, 2011; Hyman et al., 2006).. In fact, the striatum is composed of several ...
Object. Atorvastatin, a β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor, improves neurological functional outcome, reduces cerebral cell loss, and promotes regional cellular plasticity when administered after intracerebral hemorrhage (ICH) in rats.. Methods. Autologous blood was stereotactically injected into the right striatum in rats, and atorvastatin was administered orally beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2 mg/kg, atorvastatin significantly reduced the severity of neurological deficit from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum was also significantly reduced in these animals. Consistent with previous study data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome or reduce the extent of injury. Histochemical stains for markers of synaptogenesis, immature neurons, and neuronal migration revealed increased labeling in the region of hemorrhage in the atorvastatin-treated ...
Todays study seeks to research the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-B) activation and excitotoxicity in rats striatal neurons. degradation and phosphorylation, adjustments in the degrees of IKK, p-IKK, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced lack of striatal neurons were inhibited by Z-FF-FMK […]. Read More ». ...
Todays study seeks to research the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-B) activation and excitotoxicity in rats striatal neurons. degradation and phosphorylation, adjustments in the degrees of IKK, p-IKK, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced lack of striatal neurons were inhibited by Z-FF-FMK […]. Read More ». ...
Such gene polymorphisms have corresponding chemical factors and phenotypic dysfunctions. The neuroimaging analysis by Nigg and Casey, 2005, indicated that an independent or combined disruption in the frontocerebellar circuits and frontostriatal circuits resulted in an inability to maintain and adjust behaviours according to social setting and was related to the input of the prefrontal cortex (Nigg, J., Casey, B. 2005). This was supported by further neuroimaging findings on these circuits and their role in ADHD by Krain and Castellanos, 2006, Swanson and Castellanos, 2002 and Durston et al., 2003. Contrastingly, it was found that the dopamine transporter gene, DAT1, could be responsible for the short attention span issues associated with ADHD (Bellgrove et al., 2005). Although unclear, mutations of the DAT1, SLC6A3 gene is thought to potentially affect DAT1 expression, and thus lead to a deregulated DAT and thus impaired dopaminergic transmission. Currently only examined in animal models, a ...
Working in the addiction field, it is fairly common these days to read research studies that look at activation of the ventral striatum. There are also theories about which neural circuits are responsible for most aspects of addiction including the initial euphorigenic effects, acute behaviors involving positive reinforcement, and chronic compulsive effects associated with negative reinforcement. I think that there is an general conceptualization that there are varying levels of euphoria associated with activation of the ventral striatum whether that is from an addictive drug or what has been considered to be "natural" activators of the ventral striatum including food, water, sexual behavior, and social affiliation. This is the first study that I have seen showing that activation of the ventral striatum is associated with the cognitive aspects of life. In correspondence with the lead author Etienne Koechlin his group refers to this as the "Eureka Response". He suggests that the ventral striatum ...
The view that anatomically distinct memory systems differentially contribute to the development of drug addiction and relapse has received extensive support. The present brief review revisits this hypothesis as it was originally proposed 20 years ago (1) and highlights several recent developments. Extensive research employing a variety of animal learning paradigms indicates that dissociable neural systems mediate distinct types of learning and memory. Each memory system potentially contributes unique components to the learned behavior supporting drug addiction and relapse. In particular, the shift from recreational drug use to compulsive drug abuse may reflect a neuroanatomical shift from cognitive control of behavior mediated by the hippocampus/dorsomedial striatum toward habitual control of behavior mediated by the dorsolateral striatum (DLS). In addition, stress/anxiety may constitute a cofactor that facilitates DLS-dependent memory, and this may serve as a neurobehavioral mechanism underlying the
Lhermitte, F. (1986). Human autonomy and the frontal lobes. II. Patient behavior in complex and social situations. The environmental dependency syndrome. Annals of Neur Lou H, Henriksen L., Bruhn P Borner H, Nielsen J (1989): Striatal dysfunction in attention deficit and hyperkinetic disorder. Archives of Neur Lubar JF, Bianchini KJ, Calhoun WH, Lambert EW, Brody ZH, Shabsin HS (1985): Spectral analysis of EEG differences between children with and without learning disabilities. Journal of Learning Disabilities18:403-408 ...
N-methyl-d-aspartate receptor (NMDAR) subunit composition strictly commands receptor function and pharmacological responses. Changes in NMDAR subunit composition have been documented in brain disorders such as Parkinsons disease (PD) and levodopa (L-DOPA)-induced dyskinesias (LIDs), where an increase of NMDAR GluN2A/GluN2B subunit ratio at striatal synapses has been observed. A therapeutic approach aimed at rebalancing NMDAR synaptic composition represents a valuable strategy for PD and LIDs. To this, the comprehension of the molecular mechanisms regulating the synaptic localization of different NMDAR subtypes is required. We have recently demonstrated that Rabphilin 3A (Rph3A) is a new binding partner of NMDARs containing the GluN2A subunit and that it plays a crucial function in the synaptic stabilization of these receptors. Considering that protein-protein interactions govern the synaptic retention of NMDARs, the purpose of this work was to analyse the role of Rph3A and Rph3A/NMDAR complex ...
Objective: The exact role of nuclear factor-kappaB (NF- κB) in intracerebral hemorrhage (ICH) is still unclear to date. The aim of the present study is to clarify the activation of NF-κB and the role of its subunits in inflammatory response and cell death after ICH. Methods: The model of ICH rats was made, and at preset time points after operation, as well as rats in the control and sham groups, the ipsilateral striatum and tissue around was obtained for detection of NF-κB activation, cell death, and expression of interleukin-1β, tumor necrosis factor-α, Caspase-3, Bcl-2, and NF-κB subuni ...
Ah, brains: so mysterious, complicated, and powerful, and yet so inclined to tell us to sit on the couch and eat doughnuts instead of doing the dishes or working out. Whats with these things, anyway?. Theres a group of neurons deep in the heart of the brain called the basal ganglia, and theyre involved in some important functions like movement and habit formation. How does the habit formation part work? Kind of a like a big, stupid, friendly guy, whos only too willing to help but needs to be shown what to do over and over. And over. And over again. You get the idea.. So if Im out here wanting to develop a habit of remembering someones name the first time its said by always repeating it and using a mnemonic, and if I try that once or twice, the basal ganglia-our big friend-are going to be staring at me dully, wondering exactly what Im getting at. But if I stay aware with post-it notes or constant vigilance or a string tied around my finger, and if I keep at it, eventually hell get a ...
Downloadable! In an intertemporal consumption-leisure choice model with wage uncertainty, and habit-forming consumption, we have shown that, consumption and leisure do move in opposite directions, consistent with the observed pro-cyclicy of aggregate hours worked. Dans un modèle intertemporel de consommation et de loisir avec incertitude salariale et formation dhabitudes, nous avons démontré que la consommation et le loisir se déplacent vers des directions opposées, ce qui est consistant avec la procyclicité observée des heures travaillées.
Taking levitra - Stimulation of dopaminergic nerves both centrally and peripherally to block the conversion of atp to camp. The man squeezes the deflating valve or briefly bends the penis up on to the effect of treatment success.
On January 15, FSIS announced the availability of the agencys draft Establishment-Specific Data Release Strategic Plan (the draft plan) for sharing data on federally inspected meat and poultry establishments with the public. FSIS developed the plan in response to memoranda released by President Obama and the Office of Management and Budget (OMB) that called for ...
Drugs of abuse share the ability to enhance dopaminergic neurotransmission in the dorsal and ventral striatum. The action of dopamine is modulated by additional neurotransmitters, including glutamate,
The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinsons disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinsons disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This ...
Uridine (15mg/kg/day, i.p.), haloperidol (1mg/kg/day, i.p.), uridine (15mg/kg/day, i.p.) plus haloperidol (1mg/kg/day, i.p.) or saline have been chronically administered to Sprague-Dawley male rats. Following 1 week of wash-out, the effects of these treatments on basal striatal dopamine (DA) release as well as on the DA release induced by an acute haloperidol challenge (2mg/kg, i.p.) were studied by means of intracerebral microdialysis. Behavioural tests such as haloperidol-induced catalepsy or apomorphine-induced stereotypics were also performed 4-7 days after drug withdrawal. The chronic treatment with uridine alone or associated with haloperidol markedly reduced DA release induced by an acute haloperidol challenge. The behavioural studies also indicated a change in DA-related behaviours in these conditions. The animals chronically treated with uridine showed significant increases in the stereotypy scores and in the catalepsy induced by an acute haloperidol challenge with respect to saline ...
Neuronal circuits including medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and melanin-concentrating hormone (MCH)-containing neurons in the lateral hypothalamic area (LHA) are hypothesized to play an important role in hedonic feeding. A reciprocal connection between NAc MSNs and MCH-containing neurons is proposed to form a neuronal circuit that is involved in hedonic feeding. Although NAc MSNs have been shown to receive projection from MCH-containing neurons, it is not known whether MCH-containing neurons in the LHA also receive direct inputs from NAc MSNs. Here, we developed a genetic approach that allows us to visualize almost all striatal MSNs including NAc MSNs. We demonstrate that striatal MSNs terminate in a distinct region within the anterior LHA, and that the terminal area of striatal MSNs in this region contains glutamatergic neurons and is distinctly separate from orexin/hypocretin- or MCH-containing neurons. These observations suggest that NAc MSNs do not directly innervate MCH
article{7505807c-8494-4f18-8a4c-93f0b0698b1a, abstract = {Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were continuously delivered to the striatum at biologically active levels via recombinant adeno-associated viral (rAAV) gene transfer 4-5 weeks prior to 30 min of middle cerebral artery occlusion (MCAO). The magnitude of the deficits in a battery of behavioral tests designed to assess striatal function was highly correlated to the extent of ischemic damage determined by unbiased stereological estimations of striatal neuron numbers. The delivery of neurotrophins lead to mild functional improvements in the ischemia-induced motor impairments assessed 3-5 weeks after the insult, in agreement with a small but significant increase of the survival of dorsolateral striatal neurons. Detailed phenotypic analysis demonstrated that the parvalbumin-containing interneurons were spared to a greater extent by the neurotrophin treatment as compared to the projection neurons, which ...
Although neurochemical and behavioral changes associated with near-total losses of DA in striatum have been well characterized, little is known about the long-term consequences on basal ganglia function of the partial monoamine loss associated with METH-induced neurotoxicity. The present data show that 3 weeks after administration of a neurotoxic regimen of METH, SP mRNA in striatum was decreased and CO activity in the EPN and the SNr was increased. However, ENK mRNA in the striatum and neuronal activity in the GP and STN were unaltered. These data suggest that such exposure to METH results in a selective decrease in striatonigral pathway function.. Numerous studies indicate that the DA innervation of striatum is compromised following administration of high doses of METH (Hotchkiss and Gibb, 1980; Wagner et al., 1980). In the present study, dose-dependent decreases in DA tissue content and TH immunoreactivity in striatum were seen 3 weeks after administration of multiple doses of METH. At ...
TY - JOUR. T1 - Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. AU - Wirkner, Kerstin. AU - Assmann, Heike. AU - Köles, L.. AU - Gerevich, Zoltan. AU - Franke, Heike. AU - Nörenberg, Wolfgang. AU - Boehm, Rudolf. AU - Illes, Peter. PY - 2000. Y1 - 2000. N2 - 1. Whole-cell patch clamp experiments were used to investigate the transduction mechanism of adenosine A(2A) receptors in modulating N-methyl-D-aspartate (NMDA)-induced currents in rat striatal brain slices. The A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5-N-ethylcarboxamidoadenosine (CGS 21680) inhibited the NMDA, but not the (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) current in a subset of striatal neurons. 2. Lucifer yellow-filled pipettes in combination with immunostaining of A(2A) receptors were used to identify CGS 21680-sensitive cells as typical medium spiny striatal neurons. 3. Dibutyryl cyclic AMP and the protein kinase A activator Sp-cyclic ...
Abstract: "Endocannabinoids as well as their receptors play a modulatory role from the control of dopamine transmission during the basal ganglia. On the other hand, this influence is usually indirect and exerted from the modulation of GABA and glutamate inputs obtained by nigrostriatal dopaminergic neurons, which lack cannabinoid CB1 receptors Even though They might produce endocannabinoids. Added proof implies that CB2 receptors could be situated in nigrostriatal dopaminergic neurons, and that particular eicosanoid-related cannabinoids may possibly straight activate TRPV1 receptors, that have been found in nigrostriatal dopaminergic neurons, As Find Out More a try this result making it possible for in both cases a immediate regulation of dopamine transmission by unique cannabinoids. Furthermore, CB1 receptors type heteromers with dopaminergic receptors which give Yet another pathway to immediate interactions between equally methods, in this case within the postsynaptic amount ...
The team induced a mild stroke similar to a silent stroke in the striatum area of the brain in mice. They found there was inflammation and brain damage in the striatum following the stroke, which they had expected. What the researchers didnt expect was the impact on another area of the brain, the substantia nigra. When they analysed the substantia nigra they recorded a rapid loss of Substance P (a key chemical involved in its functions) as well as inflammation. The team then analysed changes in the brain six days after the mild stroke and found neurodegeneration in the substantia nigra. Dopaminergic neurones had been killed.. Talking about the findings Dr Pinteaux said: "It is well known that inflammation following a stroke can be very damaging to the brain. But what we didnt fully appreciate was the impact on areas of the brain away from the location of the stroke. Our work identifying that a silent stroke can lead to Parkinsons disease shows it is more important than ever to ensure stroke ...
Parkinsons disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations in alpha-synuclein, UCHL1 (a ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to the damage and subsequent loss of DA neurons through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum. This results in a reduced activation of the direct pathway and in a disinhibition of the indirect pathway, which is associated with the elevation of adenosine A2A receptor transmission. Such unbalanced activity of the striatal output pathway is at the basis ...
Parkinsons disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations in alpha-synuclein, UCHL1 (a ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to the damage and subsequent loss of DA neurons through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum. This results in a reduced activation of the direct pathway and in a disinhibition of the indirect pathway, which is associated with the elevation of adenosine A2A receptor transmission. Such unbalanced activity of the striatal output pathway is at the basis ...
Idiopathic PD is defined as a synucleinopathy in which Lewy bodies, pathological aggregations of the synaptic protein α-synuclein, are found in the dopaminergic neurons in the substantia nigra [14, 15]. A reduction of dopamine in the striatum is a consistent finding in PD, although the clinical features are heterogeneous and include different predominant symptoms (resting tremor, bradykinesia, rigidity, or postural instability and gait disorder) with different rates of progression, and with or without dementia [16-19]. PET imaging is a valuable tool for assessing altered dopaminergic function in the striatum in PD. While FDOPA is suitable for assessing the metabolism of levodopa, FMT is superior for estimating AADC activity because it enables the production of higher-quality brain images [7, 20-22]. The high resolution of FMT-PET images enables analysis of dopaminergic presynaptic changes in each subregion of the striatum.. In the present study, FMT uptake in PD was reduced in the putamen, ...
The Scientific World Journal is a peer-reviewed, Open Access journal covering a wide range of subjects in science, technology, and medicine. The journals Editorial Board as well as its Table of Contents are divided into 81 subject areas that are covered within the journals scope.
The striatum integrates sensory and motor information to enable action selection and behavioral reinforcement. There is a large topographical projection from the rat barrel cortex to widely distributed areas of the striatum. The response of the striatum to sensory stimuli at a network level is, however, not comprehensively understood. We used a 10Hz/100ms air puff, allowing un-damped movement of multiple whiskers, to look at functional connectivity in contralateral cortex and striatum in response to sensory stimulation. Simultaneous recordings of cortical and striatal local field potentials (LFPs) were made under isoflurane anaesthesia in 15 male Brown Norway rats. Four electrodes were placed in barrel cortex while the dorsolateral striatum was mapped with 500µm-spaced micro-electrodes spanning the left striatum medio-laterally and moved both dorso-ventrally and rostro-caudally with 500µm steps. This resulted in a maximum of 315 striatal positions per animal. Significant event-related ...
Modelling ischaemia in vitro: Effects of temperature and glucose concentration on dopamine release evoked by oxygen and glucose depletion in a mouse brain ...
Reward prediction error (RPE) signals are central to current models of reward-learning. Temporal difference (TD) learning models posit that these signals should be modulated by predictions, not only of magnitude but also timing of reward. Here we show that BOLD activity in the VTA conforms to such TD predictions: responses to unexpected rewards are modulated by a temporal hazard function and activity between a predictive stimulus and reward is depressed in proportion to predicted reward. By contrast, BOLD activity in ventral striatum (VS) does not reflect a TD RPE, but instead encodes a signal on the variable relevant for behavior, here timing but not magnitude of reward. The results have important implications for dopaminergic models of cortico-striatal learning and suggest a modification of the conventional view that VS BOLD necessarily reflects inputs from dopaminergic VTA neurons signaling an RPE.
Poster (2013, November 10). Pathologies affecting the striatum (e.g., Parkinsons and Huntingtons disease) can result in impaired habit learning abilities. Likewise, such impairments have also been observed after stroke affecting ... [more ▼]. Pathologies affecting the striatum (e.g., Parkinsons and Huntingtons disease) can result in impaired habit learning abilities. Likewise, such impairments have also been observed after stroke affecting the middle cerebral artery territory (encompassing the striatum). However, habit learning has never been investigated in animal stroke models, for which it could be a reliable measure of cognitive deficits. We thus assessed the ability to learn a habitual sequence of lever-presses using operant conditioning in mice after MCAO, one of the most common stroke models. C57Bl/6J mice underwent MCAO or sham surgery. Sensorimotor functioning was assessed using the vertical pole test, rotarod and amphetamine-induced rotation test. Habit learning was evaluated ...
The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl- D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 μg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and Sham groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/ NMDA, Sham/Sham, and control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The ...
TY - JOUR. T1 - The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. AU - Sonsalla, Patricia K.. AU - Coleman, Christal. AU - Wong, Lai Yoong. AU - Harris, Suzan L.. AU - Richardson, Jason R.. AU - Gadad, Bharathi S.. AU - Li, Wenhao. AU - German, Dwight C.. PY - 2013/12. Y1 - 2013/12. N2 - Parkinsons disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin ...
MESSRIPOUR, Manoochehr y MESRIPOUR, Azadeh. Age related interaction of dopamine and serotonin synthesis in striatal synaptosomes. Biocell [online]. 2013, vol.37, n.2, pp.17-21. ISSN 0327-9545.. Tyrosine hydroxylase and tryptophan hydroxylase are key rate limiting enzymes in the biosyn-thesis of dopamine and serotonin, respectively. Since both enzymes are active in striatum, and affected by age, this study was undertaken to investigate interaction between dopamine and serotonin synthesis in brain striatal synaptosomes of aging rat. Male Wistar rats (3 and 30 month old) were killed by decapitation and brain striatal synaptosomes were prepared by discontinuous Ficoll/sucrose gradient technique. Synaptosomes were incubated in the presence of added pargiline (monoamineoxidase inhibitor), dopamine or serotonin synthesized during 25 min was measured by HPLC, employing electrochemical detection. Dopamine synthesis in synaptosomes prepared from young animals was markedly inhibited by addition of 5 μM ...
Previous neurochemical and behavioural studies show that tyrosine depletion using a nutritionally balanced tyrosine-free amino acid mixture attenuates the dopamine-releasing and psychostimulant properties of amphetamine. Here we investigate the effect of a tyrosine-free amino acid mixture on striatal binding of [(11)C]raclopride, and amphetamine-induced [(11)C]raclopride displacement, using positron emission tomography in the rat. Rats were scanned for 60 min after an i.v. injection of approximately 11 MBq [(11)C]raclopride using a quad-HIDAC system. Amphetamine (2 mg/kg i.p., 30 min prior to scan) caused a 12% reduction in [(11)C]raclopride distribution volume ratio (DVR) compared to saline-injected controls. The tyrosine-free amino acid mixture (1 g/kg i.p.) caused a small (+7%) but statistically insignificant increase in [(11)C]raclopride DVR and attenuated, although it did not fully block, the amphetamine-induced reduction. These data are in keeping with previous neurochemical, immunocytochemical,
We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the ...
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"Chapter 5. The Corpus Striatum, Rhinencephalon, Connecting Fibers, and Diencephalon". CMSD 620 Neuroanatomy of Speech, ... In this book, he described the pineal gland and what he believed the function was, and was able to draw the corpus striatum ...
... fibers connecting the cortex with the corpus striatum; and fibers passing from the frontal lobe through the medial fifth of the ...
He described the corpora striata and optic thalami; the four orbicular eminences, with the bridge, which he first named annular ... He noted the parallel lines of the mesolobe (corpus callosum), afterwards minutely described by Félix Vicq-d'Azyr. He seems to ...
Medium spiny neurons, most neurons in the corpus striatum. Purkinje cells, huge neurons in the cerebellum, a type of Golgi I ...
Haug H, Eggers R (August 1991). "Morphometry of the human cortex cerebri and corpus striatum during aging". Neurobiol Aging. 12 ...
Wilson SAK (1914). "An experimental research into the anatomy and physiology of the corpus striatum". Brain. 36: 427-92. doi: ... Lentiform nucleus Striatum Kimura M, Kato M, Shimazaki H, Watanabe K, Matsumoto N (December 1996). "Neural information ... are prominent myelinated fibres that connect the striatum to the globus pallidus. Their distinctive appearance allows one to ...
The putamen and caudate nucleus are also collectively called the corpus striatum after their striped appearance.[65][66] ... The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural ... Examples of neocortical areas include the granular primary motor cortex, and the striate primary visual cortex. The neocortex ... "Receptive fields of single neurones in the cat's striate cortex". The Journal of Physiology. 148 (3): 574-91. doi:10.1113/ ...
However Willis' conceptualized the corpus striatum as the seat of motor power in the late 17th century. In mid-19th-century ... movement disorders were localized to striatum by Choreaby Broadbent and Jackson, and athetosis by Hammond. By the late 19th ...
They concluded that ″dopamine is concerned with the function of the corpus striatum and thus with the control of motor function ... The concentration was highest in the corpus striatum, which contained only traces of noradrenaline. Carlsson's group had ... who had been introduced to dopamine by Blaschko and was carrying out a colour reaction on extracts of human corpus striatum in ... the reaction vials containing the extracts of the Parkinson's disease striatum showed hardly a tinge of pink discoloration″. In ...
In a study on slices of rat corpus striatum and substantia nigra fencamfamin acted as an indirect dopamine agonist. It released ...
Communicata all'Academia di Medicina di Torino, 1883 - Nota preventiva on fine anatomy of the corpus striatum. Communication of ... Nota preventiva sulla fina anatomia dei corpi striati. ...
Projection tracts connect the cerebral cortex with the corpus striatum, diencephalon, brainstem and the spinal cord. The ... which connect the cerebral cortex with the corpus striatum, diencephalon, brain stem and the spinal cord Saladin, Kenneth (2012 ... Examples are the posterior commissure and the corpus callosum. A decussation is a connection made by fibres that cross at ... The great majority of commissural tracts pass through the corpus callosum. A few tracts pass through the much smaller anterior ...
The corpus striatum is the main input center of the basal ganglia, specifically upper neurons of motor areas in the frontal ... There is another indirect pathway present between the corpus striatum and part of the globus pallidus. This indirect pathway ... The basal ganglia include groups of motor nuclei located deep within the cerebral hemispheres, including the corpus striatum, ...
The view that the corpus striatum played such a large role in motor functions was the most prominent one until the 19th century ... Soon it would be discovered that the theory about the corpus striatum would not be completely incorrect. By the late 19th ... About a century later, Thomas Willis noticed that the corpus striatum was typically discolored, shrinkened, and abnormally ... John Hughlings Jackson posited that the motor cortex was more relevant to motor function than the corpus striatum after ...
The floor of the left lateral ventricle, thalamus, and corpus striatum were softened to the point of unrecognition. These ... thalamus and corpus striatum. There were similar right sided numbness in some patients, coldness of the extremities, and ...
He also noted that its large corpus striatum implied that it had a sophisticated repertoire of instinctive behaviors. He ...
Lesions to the brain are most often the direct cause of the symptoms, particularly to the corpus striatum. This symptom does ... as well as the corpus striatum; therefore children during the developmental age could possibly suffer from cognitive deficits ... The striatum receives excitatory inputs from the cortex and inhibits the pallidum. By doing so it frees the thalamus from ... "Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain ...
... in lacunar lesions of the corpus striatum]". Rev. Neurol. (Paris) (in French). 144 (10): 571-7. PMID 3194605. Carota A, Staub F ... The cause of this condition has been hypothesized to derive from abnormalities in the limbic frontal cortex, the striatum, ...
... and the vessels belonging to it supply the thalami and corpora striata; the longer is the cortical system, and its vessels ...
... which connect the cerebral cortex with the corpus striatum, diencephalon, brain stem and the spinal cord. Diagram at ...
... which connect the cerebral cortex with the corpus striatum, diencephalon, brain stem and the spinal cord. Standring, Susan ( ...
The striatum, in red, includes the caudate nucleus (top), the putamen (right), and, when including the term 'corpus' striatum, ... This is a transverse section of the striatum from a structural MR image. ... is an inherited disorder that causes progressive degeneration of neurons within the cerebral cortex and striatum of the brain[ ... brain specific histone H3 hypoacetylation and decreased histone association at specific downregulated genes within the striatum ...
4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters ... particularly in the striatum and meso-limbic system. Moreover, it is thought to "increase the release of these monoamines into ...
... to the corpus striatum (Latin, "striped body").[citation needed] This naming can extend to include any number of structures in ... Arcuate fasciculus Cerebral peduncle Corpus callosum Pyramidal or corticospinal tract Medial forebrain bundle Posterior column- ... Examples of these include the great commissures of the brain such as the corpus callosum (Latin, "hard body"; not to be ...
He did major research on the anatomy and disorders of the corpus striatum and the extrapyramidal system, and described several ...
The fibers of the anterior commissure can be traced laterally and posteriorly on either side beneath the corpus striatum into ... The corpus callosum allows for communication between the two hemispheres and is found only in placental mammals (the eutherians ... The great majority of fibers connecting the two hemispheres travel through the corpus callosum, which is over 10 times larger ... One such study supported colour perception in callosal agenesis (Those born without a corpus callosum; Barr & Corballis, 2002 ...
in 1995 that found that classical musicians between the ages of 21 and 36 have significantly greater anterior corpora callosa ... ventral striatum, midbrain, and the ventral medial prefrontal cortex. Many of these areas appear to be linked to reward, ... and a great increase in the size of the corpus callosum.[82] These fibers join together the left and right hemispheres and ... Musicians have been found to have more developed anterior portions of the corpus callosum in a study by Cowell et al. in 1992. ...
In 1911, Vogt-Mugnier rediscovered the so-called 'status marmoratus' of the corpus striatum, characterized by slow, writhing, ... in which she noted the mottled appearance of the striatum. In 1922, the Vogts defined the concept of pathoclisis through their ...
Corpus striatum definition, a mass of gray matter beneath the cortex and in front of the thalamus in each cerebral hemisphere. ... noun plural corpora striata (straɪˈeɪtə). a striped mass of white and grey matter situated in front of the thalamus in each ... corpus striatum. 1850-55; < New Latin: striated body. Dictionary.com Unabridged Based on the Random House Unabridged Dictionary ... corpus striatum. New Latin, literally: striated body. Collins English Dictionary - Complete & Unabridged 2012 Digital Edition ...
... corpus striatum explanation free. What is corpus striatum? Meaning of corpus striatum medical term. What does corpus striatum ... Looking for online definition of corpus striatum in the Medical Dictionary? ... Synonym(s): corpus striatum [TA]. corpus striatum. (strī-ā′təm). n. pl. corpora striata (strī-ā′tə) Either of two gray and ... corpus. [kor´pus] (pl. cor´pora) (L.) body.. corpus al´bicans white fibrous tissue that replaces the regressing corpus luteum ...
What is corpus striatum? Meaning of corpus striatum as a finance term. What does corpus striatum mean in finance? ... Definition of corpus striatum in the Financial Dictionary - by Free online English dictionary and encyclopedia. ... Corpus striatum financial definition of corpus striatum https://financial-dictionary.thefreedictionary.com/corpus+striatum ... corpus. (redirected from corpus striatum). Also found in: Dictionary, Thesaurus, Medical, Legal, Encyclopedia, Wikipedia. ...
History and etymology The term originates from the Latin striatus, meaning striped, referring to the caudatolenticar ... The corpus striatum is a collective name given to the caudate nucleus and lentiform nucleus. ... The corpus striatum is a collective name given to the caudate nucleus and lentiform nucleus. ... The term originates from the Latin "striatus", meaning "striped", referring to the caudatolenticar bridges of grey matter ...
These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role ... total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ - diabetic rats and the ... of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease ... The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest ...
In response to drug exposure, CREB1 is phosphorylated in the striatum, a structure that is critically involved in reward- ... By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto ... Effect of Withania somnifera supplementation on rotenone-induced oxidative damage in cerebellum and striatum of the male mice ... The roles of the medial prefrontal cortex and striatum in reputation processing. ...
li,,/ul,,ul,,li,Contain: ,/li,,/ul,,ul,,ul,,li,Corpus striatum: ,/li,,/ul,,/ul,,ul,,ul,,ul,,li,Caudate nucleus. ,/li,,/ul,,/ul ... li,,/ul,,ul,,li,Corpus callosum: ,/li,,/ul,,ul,,ul,,li,Major tract of axons that functionally interconnects right and left ... Midbrain ,ul,,li,Contains: ,/li,,/ul,,ul,,ul,,li,Corpora quadrigemina: ,/li,,/ul,,/ul,,ul,,ul,,ul,,li,Superior colliculi: ,/li ...
Corpus Striatum. *Corpus Striatum: drug effects. *Corpus Striatum: physiology. *Dopamine. *Dopamine: physiology ... In intact rats, Fos expression was increased by m-CPP (1 mg/kg, i.p.) in the striatum and the subthalamic nucleus. After ... Fos expression remained unchanged in the subthalamic nucleus but was reduced in the medial quadrants of the striatum and was ...
C Four distinct telencephalic regions were examined: a = SVZ; b = striatum; c = corpus callosum; d = peri-infarct cortex; i = ... Rare newly born mature oligodendrocytes have been reported within the striatum, corpus callosum and infarcted cortex 1 month ... Coronal sections from the Olig1-EGFP reporter mouse showed an increase in GFP+ cells 7 dpl within the striatum: control (A), ... In contrast to GFP findings, immunofluorescence for Olig1 did not show an increase in Olig1+ cells 7 dpl within the striatum: ...
... corpus callosum; LV, lateral ventricle; S, septum; Str, striatum. Scale bars: b, 50 μm; c, 20 μm; d, 10 μm. ... corpus callosum; S, septum; Str, striatum. Scale bars: a-d, 200 μm; e, f, 50 μm. ... The hypercellular nodules in the contralateral SVZ remained prominent (h). *, Lateral ventricle; CC, corpus callosum; Str, ... Consequently, no evidence of dopaminergic (DA) neurogenesis was found in the striatum or substantia nigra in any experimental ...
"Chapter 5. The Corpus Striatum, Rhinencephalon, Connecting Fibers, and Diencephalon". CMSD 620 Neuroanatomy of Speech, ... In this book, he described the pineal gland and what he believed the function was, and was able to draw the corpus striatum ...
Stereologic analysis of the development of the corpus striatum between the 14th and 19th week of gestational age ... Stereologic analysis of the development of the corpus striatum between the 14th and 19th week of gestational age. ... Stereologic analysis of the development of the corpus striatum between the 14th and 19th week of gestational age. Medicinski ...
Rostral Commissure and Corpus Striatum; Optic Chiasm and Telencephalon; Habenular Nucleus and Piriform Lobe; Mamillary Nucleus ... Examples of "Canine Brain Atlas Transverse" Sections include "...Septum and Striate Body; ...
Keywords: P-pABA modified electrode (ME); Monoamines; HPLC-ECD; Microdialysis; Effect of NO; Rat corpus striatum; ... was performed into rat striatum, which increased striatal DA release with 1.5-fold to the basal level. ...
In contrast to the SVZ, other areas analyzed at the same anatomical level [i.e., the corpus callosum, striatum, and septum ( ... corpus callosum; LV, lateral ventricle; St, striatum; Sept, septum. Scale bars: C , 50 μm; D , 300 μm; E , 10 μm. ... Corpus callosum; St, striatum; LV, lateral ventricle. Note the highly organized aspect of the SVZ in the control animal ... The corpus callosum in both Ad:LIF and Ad:LacZ mice contains some GFP+ cells, likely because of the lesion induced at the time ...
PL, Prelimbic cortex; IL, infralimbic cortex; DM, dorsomedial striatum; cc, corpus callosum; arrowheads, midline. Scale bars, ... c-Fos-positive neurons in medial prefrontal cortex and dorsomedial striatum in amphetamine-treated Adcyap1−/− mice. A, Number ... Amphetamine-induced increase in the number of c-Fos-positive neurons in the dorsomedial striatum (Fig. 6) and other regions, ... B, Photomicrographs showing representative c-Fos labeling in medial prefrontal cortex (top panels) and dorsomedial striatum ( ...
The primary efferent outflow from the corpus striatum 116 What does the basal ganglia play a key role in? ...
What develops from the corpus striatum? (neuroepithelial layer--, mantle layer (ventral part of wall)--, corpus striatum--,?). ...
corpus striatum. two changes that occur at the cellular level in the formation of new ____, or changes in the strength of the ...
Corpus Striatum. Striped gray and white matter consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located ...
... the molecular mechanisms that govern striatum function are not fully understood. The extracellular signal regulated kinase (ERK ... The striatum is critical for learning and decision making; however, ... Corpus Striatum / physiology*. Extracellular Signal-Regulated MAP Kinases / metabolism*. Neuronal Plasticity / physiology. ... The striatum is critical for learning and decision making; however, the molecular mechanisms that govern striatum function are ...
Corpus Striatum / physiopathology. Family. Female. Frontal Lobe / physiopathology*. Functional Neuroimaging. Gyrus Cinguli / ... and the striatum.. RESULTS: The authors observed increased activation in response to reward and reward reversal contingencies ...
Corpus Striatum / metabolism* * Dopamine / genetics* * Dopamine / metabolism * Dopamine Plasma Membrane Transport Proteins / ...
  • This has been noted in the human striatum following an ischemic stroke. (wikipedia.org)
  • Dopaminergic Modulation of the Functional Ventrodorsal Architecture of the Human Striatum. (bioportfolio.com)
  • Using systematic pharmacological manipulation of dopamine D2-receptors and resting-state functional imaging, we defined the functional architecture of the human striatum and quantified the effects of dopaminergic drugs on intrinsic effective connectivity between striatal subregions. (bioportfolio.com)
  • ERK is activated in the striatum by coordinated dopamine and glutamate receptor signaling, where it underlies corticostriatal synaptic plasticity and influences striatal cell excitability. (biomedsearch.com)
  • Levodopa increases dopamine concentration in the striatum, especially when its peripheral metabolism is inhibited by a peripheral decarboxylase inhibitor (PDI). (holisticonline.com)
  • ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. (biomedcentral.com)
  • In addition, several serotonin receptors are highly expressed in the striatum and available to modify the action of L-DOPA. (innovations-report.com)
  • This behavioral effect was associated with preserved activity of CB1Rs regulating GABA transmission in the striatum, whereas these receptors were dramatically down-regulated by stress in control animals. (aspetjournals.org)
  • We conclude that continuous supply of trophic factors by means of genetically modified neural stem cells represents a highly effective procedure to counteract neuronal degeneration in the excitotoxically lesioned striatum. (nih.gov)
  • In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ - diabetic rats and the insulin treated diabetic rats. (biomedcentral.com)
  • When the researchers gave these mice L-DOPA, they found increased levels of the serotonin 1B receptor and the protein p11 in the striatum. (innovations-report.com)
  • To begin to elucidate the mechanisms of functional selectivity, my experiments will focus on the actions of DHX on D2 receptor functions in rat striatum. (elsevier.com)
  • Collectively, our findings suggest that preservation of cannabinoid CB1 receptor function within the striatum is a possible synaptic correlate of the antianxiety effects of FAAH inhibition. (aspetjournals.org)
  • As judged by morphological and neurological data, the effect of ischemia is also apparent in the presumed less vulnerable regions (CA3 and striatum) which are functionally important in stroke plasticity. (curehunter.com)
  • The astroglial and microglial reactions to the excitotoxic lesion were substantially reduced in the striata, which had received transplants of NGF-producing cells. (nih.gov)
  • The corpus striatum showed a significant atrophy strongly correlating with clinical symptoms. (tum.de)
  • The reasons for this are incompletely understood, though the fact that parts of the striatum lie at the boundary of the arterial supply from the anterior and middle cerebral arteries may be significant. (bmj.com)
  • Divac, I.: Drug-induced syndrome in rats with large, chronic lesions in the corpus striatum. (springer.com)
  • Immunohistochemical techniques were used to quantify cell density of neuronal and glial components of the corpus striatum in eight South African Mn mine workers without clinical evidence of a movement disorder and eight age-race-gender matched, non-Mn mine workers. (cdc.gov)
  • The normal passage of SVZ neuroblasts is to the olfactory bulb but this traffic is diverted to the striatum after an ischemic stroke. (wikipedia.org)
  • Dysregulation of ERK signaling in the striatum by repeated drug exposure contributes to the development of addictive behavior. (biomedsearch.com)
  • These results highlight the importance of ERK signaling in the striatum as a critical substrate for learning and as a regulator of ongoing behavior. (biomedsearch.com)
  • In mid-19th-century movement disorders were localized to striatum by Choreaby Broadbent and Jackson, and athetosis by Hammond. (wikipedia.org)
  • Administration of tetrahydrobiopterin restored the decline of dopamine in the striatum induced by an acute action of MPTP. (bioportfolio.com)
  • Acute intraparenchimal hemorrhage (bleeding) in the left corpus striatum with minimal focal mass effect on NECT. (radiologyinfo.org)
  • Damage may be widespread, though the corpus striatum seems particularly vulnerable. (bmj.com)
  • Normally, the dopamine transmits signals to the corpus striatum, allowing muscles to make smooth, controlled movements. (medgadget.com)