Striatal output neurons (SONs) integrate glutamatergic synaptic inputs originating from the cerebral cortex. In vivo electrophysiological data have shown that a prior depolarization of SONs induced a short-term (1 sec)increase in their membrane excitability, which facilitated the ability of corticostriatal synaptic potentials to induce firing. Here we propose, using a computational model of SONs, that the use-dependent, short-term increase in the responsiveness of SONs mainly results from the slow kinetics of a voltage-dependent, slowly inactivating potassium A-current. This mechanism confers on SONs a form of intrinsic short-term memory that optimizes the synaptic inputâ€output relationship as a function of their past activation ...

TY - JOUR. T1 - c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats. AU - Dela Cruz, J. A. D.. AU - Coke, T.. AU - Karagiorgis, T.. AU - Sampson, C.. AU - Icaza-Cukali, D.. AU - Kest, K.. AU - Ranaldi, R.. AU - Bodnar, R. J.. PY - 2015/2. Y1 - 2015/2. KW - Ventral tegmental area. KW - Basolateral amygdala. KW - Central-cortico-medial amygdala. KW - Prelimbic medial prefrontal cortex. KW - Infralimbic medial prefrontal cortex. KW - Nucleus accumbens core. KW - Nucleus accumbens shell. KW - Dorsal striatum. U2 - 10.1016/j.brainresbull.2014.11.002. DO - 10.1016/j.brainresbull.2014.11.002. M3 - Article. C2 - 25460109. VL - 111. SP - 9. EP - 19. JO - Brain Research Bulletin. JF - Brain Research Bulletin. SN - 0361-9230. ER - ...

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

Fingerprint Dive into the research topics of Generation of Human Striatal Neurons by MicroRNA-Dependent Direct Conversion of Fibroblasts. Together they form a unique fingerprint. ...

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. ...

Understanding neural representations of behavioral routines is critical for understanding complex behavior in health and disease. We demonstrate here that accentuated activity of striatal projection neurons (SPNs) at the beginning and end of such behavioral repertoires is a supraordinate representat …

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

耶魯大學的團隊，透過偵測大鼠大腦的基底節（basal ganglia)紋狀體區（striatal areas）的多巴胺（dopamine）分泌後發現，紋狀體區的背側（dorsal striatal sector，DS）負責對糖的能量進行反應，而紋狀體區的腹側（ventral striatal sector，VS）則負責對糖的甜味進行反應。. 當以葡萄糖餵食大鼠時，大鼠的紋狀體背區與紋狀體腹區都分泌多巴胺；而以人工甘味（蔗糖素，sucralose，為所有人工甘味中口味最接近天然糖的）餵食大鼠時，大鼠只有紋狀體腹區分泌多巴胺。而當研究團隊以苦味劑苯甲地那銨（denatonium benzoate，全世界最苦的化合物，即使只有10 ppm ...

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 ...

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Postmortem volumetry of the human striatum and its subdivisions (putamen, n.caudatus, n.accumbens) was performed on serial coronal sections of complete hemispheres. Both hemispheres of 9 male schizophrenic patients younger than 65 years were closely matched in age with the hemispheres of 9 male cont …

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 ...

E18 Mouse Striatum, Primary Cells, Primary Neurons, Cell Assays. Fresh E18 intact Striatum from a C57/BL6 mouse with media provided to maintain the cells while being shipped. Media is also included to initiate a culture. 3.8 Million Cells.

The ventral striatum is a relatively small area tucked deep inside the brain near the basal ganglia. Until recently, not much was known about it. But its recently been linked to reward, decisions, and risk, and as a result is getting much more press than it used to. Its important in what we perceive as rewarding (such as status and keeping up with the Joneses) and how rewarding it is. Its been linked to pathological gambling, and it matters when youre thinking about what to do next with your portfolio.. The ventral striatum consists of two portions, the nucleus accumbens and the olfactory tubercle. Its most important neurotransmitter-to our current knowledge-is dopamine. Dopamine is associated with pleasure and with motor functions. (Dopamine-increasing drugs are used to treat Parkinsons disease.) The ventral striatum is closely linked with the limbic system, which involves emotion and motivation: it receives input from it and sends output to it, mainly inhibitory. Its thought that the ...

Sentence processing takes place in real-time. Previous words in the sentence can influence the processing of the current word in the timescale of hundreds of milliseconds. Recent neurophysiological studies in humans suggest that the fronto-striatal system (frontal cortex, and striatum - the major input locus of the basal ganglia) plays a crucial role in this process. The current research provides a possible explanation of how certain aspects of this real-time processing can occur, based on the dynamics of recurrent cortical networks, and plasticity in the cortico-striatal system. We simulate prefrontal area BA47 as a recurrent network that receives on-line input about word categories during sentence processing, with plastic connections between cortex and striatum. We exploit the homology between the cortico-striatal system and reservoir computing, where recurrent frontal cortical networks are the reservoir, and plastic cortico-striatal synapses are the readout. The system is trained on sentence-meaning

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, ...

function out = RunSimulation(SIMPARAMS) % set the path to the simulation files addpath(pwd, [pwd /Simulation]); % these are currently redundent parameters that may be required again when % I put the cortical pulse code back into the simulation SIMPARAMS.CTX_state = [1 1 0 0 0 0 0 0]; SIMPARAMS.initCTX = rand(2); % check the parameter types before calling the c++ funciton checkStriatumInputs(SIMPARAMS); % Run the simulation - using original version: as per NN model % Run the simulation - using version striatum_RK2_B: no scaling of synaptic input by 1/ts [out.t, out.Vms, out.Vfs, out.STms, out.STfs, out.VMS, out.UMS, out.VFS, out.UFS, out.VFSGAP, out.MSGLU_AMPA, out.MSGLU_NMDA, out.MSGABA, out.MSSEQ, out.FSGLU, out.FSGABA, out.FSSEQ, out.RecordChan_MS] = ... striatum_RK2(SIMPARAMS.sim.tstart,SIMPARAMS.sim.tfinal,... SIMPARAMS.sim.dt, ... SIMPARAMS.physiology.MSparams,SIMPARAMS.physiology.FSparams,... SIMPARAMS.physiology.Eglu, SIMPARAMS.physiology.Egaba, SIMPARAMS.physiology.ts_glu_AMPA, ...

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

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TY - CHAP. T1 - Organization of Prefrontal-Striatal Connections. AU - Groenewegen, HJ. AU - Wouterlood, FG. AU - Uylings, HBM. PY - 2017. Y1 - 2017. N2 - This chapter describes the organization of the prefrontal-striatal projections. There exists a topographical relationship in these projections, such that sensorimotor cortices project to the dorsolateral part of the striatum, associative cortical regions to more ventral and medial regions, and the limbic cortical areas to the most ventromedial striatal areas. Whereas the parallel, segregated nature of these projections has been emphasized for a long time, more recent studies, taking into account the so-called focal and diffuse types of termination of cortical afferents in the striatum, show that there is considerable overlap between projections from different prefrontal cortical projection areas in the striatum. This allows for specific integration of information. Further, the relationship of the prefrontal cortex with the striatal ...

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- ...

Take the eduMIP and hook it up with the DSTR app in order to control the Mobile Inverted Pendulum from your very own cell phone!. Find this and other hardware projects on Hackster.io.

TY - JOUR. T1 - Functional connectome of the striatal medium spiny neuron. AU - Chuhma, Nao. AU - Tanaka, Kenji F.. AU - Hen, René. AU - Rayport, Stephen. PY - 2011/1/26. Y1 - 2011/1/26. N2 - Dopamine system disorders ranging from movement disorders to addiction and schizophrenia involve striatal medium spiny neurons (MSNs), yet their functional connectivity has been difficult to determine comprehensively. We generated a mouse with conditional channelrhodopsin-2 expression restricted to medium spiny neurons and assessed the specificity and strength of their intrinsic connections in the striatum and their projections to the globus pallidus and the substantia nigra. In the striatum, medium spiny neurons connected with other MSNs and tonically active cholinergic interneurons, but not with fast-spiking GABA interneurons. In the globus pallidus, medium spiny neurons connected strongly with one class of electrophysiologically identified neurons, but weakly with the other. In the substantia nigra, ...

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. ...

TY - JOUR. T1 - Striatal dopamine release during unrewarded motor task in human volunteers. AU - Badgaiyan, Rajendra D.. AU - Fischman, Alan J.. AU - Alpert, Nathaniel M.. PY - 2003/8/6. Y1 - 2003/8/6. N2 - Striatal dopamine is associated with the processing of rewarded motor tasks. Its involvement in mediating unrewarded tasks is, however, unclear. We used a recently developed PET technique to dynamically measure the rate of displacement of a dopamine receptor ligand raclopride in healthy volunteers performing a finger opposition task. Rapid displacement of the ligand from the posterior putamen and the caudate immediately after the task initiation suggested striatal dopamine release during task performance. Since dopamine release was observed in the striatal areas that are implicated in unrewarded tasks by neuroimaging studies, the results demonstrate that the PET method can be used to extend the findings of conventional neuroimaging techniques, that do not provide information about signal ...

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 ...

In this study we examined the stereoselectivity of catecholamine uptake into synaptosomes prepared from rat cerebral cortex or corpus striatum with isomers of ephedrine, methylphenidate and phenyl-2-piperidyl carbinol, compounds possessing two asymmetric carbons, hence, four possible stereoisomers. The four ephedrine isomers were more potent inhibitors of catecholamine uptake in the cerebral cortex than in the corpus striatum. There was a 100-fold variation in potency among the ephedrine isomers in the cerebral cortex but only a 7-fold variation in the corpus striatum. The optimal configuration at the α (S) and β(R) carbons (erythro configuration) for activity of the ephedrines in both brain regions corresponds to the configurations of (+)-amphetamine and (-)-norepinephrine, respectively. In contrast, the four phenyl-2-piperidyl carbinol isomers were more potent in the corpus striatum than in the cerebral cortex, and the configuration of the most potent isomer was R at both α and β carbons, ...

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 ...

Our previous findings reveal that A2A and D2 receptors are co-expressed on adult rat striatal astrocytes and on the astrocyte processes, and that A2A-D2 receptorCreceptor conversation can control the release of glutamate from your processes. (and that these heteromers can play functions in the control of the striatal glutamatergic transmission) may shed light on the molecular mechanisms involved in the pathogenesis of the disease. = 3). (B) Aliquots (300 g) of Triton X-100-soluble proteins obtained from gliosomes were immunoprecipitated with 1 g of anti-D2 antibody as explained in Methods. IP and Output were analyzed by immunoblotting using the anti-D2 antibody. IP and Output were also analyzed using anti-A2A antibody. A representative blot (of three) is usually shown. A2A immunoreactive bands were quantified and the data were reported in the graph. Values are means SEM (= 3). 2.2. D2 and A2A Receptors Expressed on Striatal Astrocytes Can Form Heteromers As illustrated in Physique 2 astrocytes ...

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.

Like the hippocampus, the striatum receives excitatory afferents from the cerebral cortex but, in the case of the striatum, very little is known about the molecular events associated with plasticity after lesions of this pathway. Using immunohistochemical techniques, we have examined the effects of cortical lesions induced either by aspiration of the frontoparietal cortex or by thermocoagulation of pial blood vessels on axonal and glial molecules associated with neuronal plasticity in the striatum. The growth associated protein GAP-43, a molecule present in axons and growth cones, decreased in the dorsolateral striatum after aspiration but not after thermocoagulatory lesions. In contrast, synaptophysin, a marker of synaptic vesicles, remained unchanged in the denervated striatum after both types of lesions. Immunostaining for basic fibroblast growth factor (bFGF) markedly decreased in striatal astrocytes after both lesions, despite an increased staining for glial fibrillary acidic protein (GFAP). The

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., ...

p,Striatal interneurons display a morphological and chemical heterogeneity that has been particularly well characterized in rats, monkeys and humans. By comparison much less is known of striatal interneurons in mice, although these animals are now widely used as transgenic models of various neurodegenerative diseases. The present immunohistochemical study aimed at characterizing striatal interneurons expressing calretinin (CR) in mice compared to those in squirrel monkeys and humans. The mouse striatum contains both small (9-12 μm) and medium-sized (15-20 μm) CR+ cells. The small cells are intensely stained with a single, slightly varicose and moderately arborized process. They occur throughout the striatum (77±9 cells/mm(3)), but prevail in the area of the subventricular zone and subcallosal streak, with statistically significant anteroposterior and dorsoventral decreasing gradients. The medium-sized cells are less intensely immunoreactive and possess 2-3 long, slightly varicose and poorly ...

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, ...

L1 antigen promotes neurite outgrowth from dopaminergic neurons in tissue culture. In the present study, we examined the effects of dopaminergic deafferentation of the striatum on L1 expression. In the medial-periventricular part of the striatum, both complete and partial substantia nigra (SN) lesions decreased L1 expression. Complete lesions increased L1 expression in the dorso-medial and ventrolateral parts of the striatum on the lesioned side when compared with that on the non-lesioned side. The decrease in the ventro-lateral area was maintained in animals examined three months after the lesioning. Animals with partial SN lesions showed a different pattern of altered L1 expression. After frontal cortex lesions, changes in L1 expression also occur preferentially in the dorso-medial and periventricular striatum. Therefore, the results indicate a complex regulation of L1 expression after damage of striatal circuitry, manifested by a preferential occurrence of changes in periventricular regions.

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 ...

The striatum, a major component of the basal ganglia, performs multiple functions including control of movement, reward, and addiction. Dysfunction and death of striatal neurons are the main causes for the motor disorders associated with Huntingtons disease (HD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is among factors that promote survival and proper function of this neuronal population. Here, we review recent studies showing that BDNF determines the size of the striatum by supporting survival of the immature striatal neurons at their origin, promotes maturation of striatal neurons, and facilitates establishment of striatal connections during brain development. We also examine the role of BDNF in maintaining proper function of the striatum during adulthood, summarize the mechanisms that lead to a deficiency in BDNF signaling and subsequently striatal degeneration in HD, and highlight a potential role of BDNF as a therapeutic target for HD treatment.

Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling Journal Article ...

G. C. TOMBAUGH, S. GELMAN, A. BRADAIA, K. WADEL, V. GARDES, C. TOULLER, A. SERS, A. GHAVAMI, B. BUISSON, G. BATES, M. MIELCAREK, C. DOMINGUEZ, M. MAILLARD, V. BEAUMONT. Huntingtons disease (HD) is a lethal autosomal dominant neurodegenerative disorder that leads to deficits in motor control widely believed to reflect structural and/or functional changes in neurons of the basal ganglia. In-vitro brain slice recordings of both the R6/2 and Q175 mouse models of HD have revealed a paucity of glutamatergic innervation of the striatum as well as alterations in intrinsic membrane properties of striatal medium spiny neurons (MSNs, exemplified by a large increase in membrane resistance (Rm) and a reduced rheobasic current (Rh). Such changes are reflective of corticostriatal pathway degeneration and MSN hyper-excitability and are likely to result in aberrant striatal output. A 50 % reduction in HDAC4 restored these and other electrophysiological changes in both the R6/2 model, a transgenic over-expresser ...

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.

In this chapter, we develop a model of μ- and δ-opioid receptor (OR) effects on cellular activity in the corticostriatal circuit after reviewing clinical data on cognitive and mood impairments in opioid substance use disorder (OUD), we use this model to derive information on the relevance of opioid actions in this circuit for cognition and reward. We find that the cognitive impairments and rewarding properties of acute μ-OR activation can reasonably explained by pharmacological actions in the corticostriatal circuit. However, long-term cognitive impairments and mood dysfunction observed in OUD are probably induced by opiate abuse-related degenerative mechanisms. ...

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. ...

In the striatum dopamine receptors are mainly situated on postsynaptic striatal neurons and thus dopamine receptor binding indirectly reflects the state of striatal neurons. In PD the striatum is relatively well preserved whereas in MSA, PSP and corticobasal degeneration (CBD) there is striatal degeneration. Therefore, in PD D2 binding is generally normal (or even shows initial upregulation) but is reduced in MSA and PSP.1,23 In CBD the impairment of dopaminergic system is asymmetrical, usually also affecting the caudate nucleus in addition to the putamen, as can be seen as reduced FDOPA uptake whereas D2 receptor binding is less consistently affected.24-26. Fluorodeoxyglucose (FDG) is a glucose analogue the up-take of which indirectly reflects neuronal and synaptic activity. Striatal FDG uptake in PD is normal (or even hypermetabolism at early stage may be seen). In contrast, in MSA, already at early stage of the disease striatal FDG uptake is reduced indicating striatal neuronal dysfunction ...

Dopamine (DA) release varies within subregions and local environments of the striatum, suggesting that controls intrinsic and extrinsic to the DA fibers and terminals regulate release. While applying fast-scan cyclic voltammetry and using tonic and phasic stimulus trains, we investigated the regulation of DA release in the dorsolateral to ventral striatum. The ratio of phasic-to-tonic-evoked DA signals varied with the average ongoing firing frequency, and the ratio was generally higher in the nucleus accumbens (NAc) compared with the dorsolateral striatum. At the normal average firing frequency, burst stimulation produces a larger increase in the DA response in the NAc than the dorsolateral striatum. This finding was comparable whether the DA measurements were made using in vitro brain slices or were recorded in vivo from freely moving rodents. Blockade of the dopamine transporters and dopamine D2 receptors particularly enhanced the tonic DA signals. Conversely, blockade of nicotinic ...

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. ...

Top 10 tissues for 38921_at (Homo sapiens, Affymetrix Probeset): associative striatum, dorsal striatum, putamen, striatum, corpus striatum, basal ganglia, mesenchymal stem cell derived adipocyte, lateral thalamic nucleus, accumbens nucleus, posterior superior temporal gyrus (Brodmann area 22)

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, ...

However, two recent repor ts challenge this interpretation by demonstrating that fusion is responsible for the appearance of donorder ived neurons after systemic administration of bone marrow cells. Recent findings in rodents suggest an alternative approach to cell therapy in stroke based on selfrepair. These immature neurons migrate into the damaged striatum, where they express markers of striatal medium spiny projection neurons.Thus, the new neurons seem to Aniracetam differentiate into the phenotype of most neurons destroyed by the ischemic lesion.However, because of the new neurons die during the first weeks after stroke, they only replace a small fraction of the mature striatal neurons that have died.Several factors can increase adult neurogenesis by stimulating formation andor improving survival of new neurons, including fibroblast growth factor, stem cell factor, erythropoietin, brainderived neurotrophic factor, caspase inhibitors and antiinflammatory drugs. Whether the new neurons formed ...

To understand the principles of operation of the striatum it is critical to elucidate the properties of the main excitatory inputs from cortex and thalamus, as well as their ability to activate the main neurons of the striatum, the medium spiny neurons (MSNs). As the thalamostriatal projection is

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] ...