(1/69) Plasticity of temporal information processing in the primary auditory cortex.
Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone sequences faster than 12 pulses per second (pps). To test whether experience can modify this maximum following rate in adult rats, trains of brief tones with random carrier frequency but fixed repetition rate were paired with electrical stimulation of the nucleus basalis (NB) 300 to 400 times per day for 20-25 days. Pairing NB stimulation with 5-pps stimuli markedly decreased the cortical response to rapidly presented stimuli, whereas pairing with 15-pps stimuli significantly increased the maximum cortical following rate. In contrast, pairing with fixed carrier frequency 15-pps trains did not significantly increase the mean maximum following rate. Thus this protocol elicits extensive cortical remodeling of temporal response properties and demonstrates that simple differences in spectral and temporal features of the sensory input can drive very different cortical reorganizations. (+info)
(2/69) Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories.
The basal forebrain complex, which includes the nucleus basalis magnocellularis (NBM), provides widespread cholinergic and gamma-aminobutyric acid-containing projections throughout the brain, including the insular and pyriform cortices. A number of studies have implicated the cholinergic neurons in the mediation of learning and memory processes. However, the role of basal forebrain activity in information retrieval mechanisms is less known. The aim of the present study is to evaluate the effects of reversible inactivation of the NBM by tetrodotoxin (TTX, a voltage-sensitive sodium channel blocker) during the acquisition and retrieval of conditioned taste aversion (CTA) and to measure acetylcholine (ACh) release during TTX inactivation in the insular cortex, by means of the microdialysis technique in free-moving rats. Bilateral infusion of TTX in the NBM was performed 30 min before the presentation of gustative stimuli, in either the CTA acquisition trial or retrieval trial. At the same time, levels of extracellular ACh release were measured in the insular cortex. The behavioral results showed significant impairment in CTA acquisition when the TTX was infused in the NBM, whereas retrieval was not affected when the treatment was given during the test trial. Biochemical results showed that TTX infusion into the NBM produced a marked decrease in cortical ACh release as compared with the controls during consumption of saccharin in the acquisition trial. Depleted ACh levels were found during the test trial in all groups except in the group that received TTX during acquisition. These results suggest a cholinergic-dependent process during acquisition, but not during memory retrieval, and that NBM-mediated cholinergic cortical release may play an important role in early stages of learning, but not during recall of aversive memories. (+info)
(3/69) Effects of huperzine A on nucleus basalis magnocellularis lesion-induced spatial working memory deficit.
AIM: To study the effects of huperzine A on nucleus basalis magnocellularis (NBM) lesion-induced spatial working memory impairment. METHODS: A delayed-non-match-to-sample radial arm maze task was used to study spatial working memory. The choline acetyltransferase (ChAT) activity was determined by the conversion of [3H]acetyl-CoA to [3H]ACh. RESULTS: Unilateral NBM lesion by kainic acid 0.02 mumol impaired rat's ability to perform this working memory task as evidenced by fewer correct choices after different delay intervals and more total errors to complete the task. This behavioral impairment associated with a decrease in the activity of ChAT by about 40% in the ipsilateral cerebral cortex. Huperzine A (0.2 mg.kg-1 i.p. 30 min before testing) ameliorated this spatial working memory impairment. Physostigmine (0.2-0.3 mg.kg-1 i.p. 20 min before testing) also attenuated the NBM lesion-induced memory deficit. CONCLUSION: The integrity of NBM is critical for spatial working memory processing, and this working memory impairment induced by NBM lesion can be ameliorated by huperzine A and physostigmine. (+info)
(4/69) Functional blockade of tyrosine kinase A in the rat basal forebrain by a novel antagonistic anti-receptor monoclonal antibody.
We have exploited a new monoclonal antibody against the tyrosine kinase A (TrkA) nerve growth factor (NGF) receptor to block the NGF-TrkA interaction in the rat basal forebrain. The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of NGF to TrkA in a variety of systems. This antibody was used to study the maintenance of the cholinergic phenotype in the rat basal forebrain in vivo, by the implant of antibody-secreting cells. Basal forebrain cholinergic neurons (BFCNs) are greatly affected by the antibody treatment, both in terms of cell number and of cell soma size. When antibody-secreting cells are implanted at postnatal day 2 (P2), the effects observed at P8 are as severe as those obtained with anti-NGF antibodies and, interestingly, are observed also if anti-TrkA cells are implanted at P8, when anti-NGF antibodies, delivered by the same route, are no longer effective (). The effects induced by anti-TrkA, as those induced by anti-NGF, are reversible, but the time required for recovery and the critical period in the sensitivity of BFCNs to the functional inactivation of TrkA is twice as long than that observed when NGF is intercepted. These results demonstrate that BFCNs are more sensitive to the block of TrkA activation than they are to the block of NGF. The cloning of MNAC13 variable regions and their assembly into a functional polypeptide of reduced size (single chain Fv fragment) will allow its use in gene transfer applications. (+info)
(5/69) Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?
The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conducted using behaviorally uncharacterized animals from the same breeding colony. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75NTR receptor has been applied to identify cholinergic cells in the structures of basal forebrain (BF). Using a quantitative image analyzer, morphometric and densitometric parameters of ChAT- and p75NTR-positive cells were measured immediately after cessation of NGF infusion. In 28-month-old non-treated rats the number of intensively ChAT-positive cells in all forebrain structures was reduced by 50-70% as compared with young animals. The remaining ChAT-positive cells appeared shrunken and the neuropil staining was NTR markedly reduced. In contrast, the same neurons when stained for p75 were numerous and distinctly visible with perfect morphology. Analysis of Nissl stained sections also showed that 28-month-old rats did not display significant losses of neuronal cell bodies. NGF restored the number of intensely stained ChAT-positive cells to about 90% of that for young controls and caused a significant increase in size of those cells in 28-month-old rats as compared with the control, age-matched group. NGF did not influence the morphology of p75NTR-positive neurons, which were well labeled, irrespective of treatment and age of the rats. In 4-month-old rats, NGF infusion decreased the intensity of both ChAT and p75NTR immunostaining. These data provide some evidence for preservation of BF cholinergic neurons from atrophy during aging and indicate that senile impairment of the cholinergic system in rats concerns decrease in ChAT-protein expression rather than an acute degeneration of neuronal cell bodies. Treatment with NGF resulted in restoration of cholinergic phenotype in the BF neurons of aged rats. However, the present study also rises issue of possible detrimental effects of NGF in young normal animals. (+info)
(6/69) The synchronizing influence of Substantia Innominata on the thalamus of the cat.
We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the waking state, on the 'central' part of the Mediodorsal nucleus of the thalamus (MD), combining electrophysiological and anatomical techniques in restrained, undrugged, unanaesthetized cats. Thalamic MD units were recorded, after electrical stimulation of the Substantia Innominata, at 1 Hz, with a single pulse or short trains of four pulses. Responses were studied by poststimulus histograms. In about 64 of the 84 recorded MD neurones (76%), stimulation of the Substantia Innominata, during the waking state, induced a brief cell excitation, followed first by prolonged inhibition of firing and then by a strong excitatory rebound discharge; after this comes a second sequence of inhibition and excitation, of decreasing amplitude. After stimulation of the Substantia Innominata, the MD units tended to start a repetitive discharge at 4--7 Hz. To investigate the connections of Substantia Innominata cells upon the areas where MD units were recorded we injected horseradish peroxidase wheat germ agglutinin (WGA-HRP), combined with immunohistochemistry for glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT). Of the total population of retrogradely labelled cells in the Substantia Innominata 53% were GAD positive while less than 16% were ChAT positive. The GAD positive MD-projecting cells in the Substantia Innominata were triangular to fusiform and small to medium in size. These findings indicate that GABAergic input from the Substantia Innominata may contribute to increasing the hyperpolarizing inhibitory pressure on MD cells in the 'central' part during slow wave sleep (SWS). (+info)
(7/69) Zinc inhibition of group I mGluR-mediated calcium homeostasis in auditory neurons.
Zinc is widely distributed in the central nervous system (CNS), it functions normally as a synaptic modulator, and it contributes to neuronal death under pathologic conditions. Zinc colocalizes with glutamate in excitatory synapses, and the presence of zinc is well characterized in the synapses of the auditory system. Since chick cochlear nucleus neurons depend upon synaptic activation of metabotropic glutamate receptors (mGluRs) for maintenance and survival, the goal of this study was to determine (1) if zinc is released from the eighth nerve calyces onto nucleus magnocellularis (NM) neurons in the chick cochlear nucleus, and, if so, (2) what effect it has on group I mGluR-mediated calcium homeostasis of these neurons. Using in vitro slices and a fluorescent dye relatively specific to vesicularized zinc, we show that zinc is indeed localized to the presynaptic calyces and is released upon nerve stimulation or KCl depolarization. Experiments employing fura-2 calcium imaging show that zinc inhibits group I mGluR release of calcium from internal stores of NM neurons and disrupts activity-dependent calcium homeostasis in a manner identical to the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine. The mGluR1-specific antagonist 7-hydroxyiminocyclopropan-[b]chromen-la-carboxylic acid ethyl ester did not affect release of calcium from stores by the nonspecific mGluR agonist aminocyclopentane dicarboxylic acid, nor did it affect activity-dependent calcium homeostasis. We conclude that zinc is present in and released from the glutamatergic eighth nerve calcyes. The presence of zinc inhibits mGluR5, a major component of calcium homeostasis of NM neurons, and plays a modulatory role in the activity-dependent, mGluR-mediated calcium homeostasis of auditory neurons. (+info)
(8/69) MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia.
BACKGROUND AND PURPOSE: The substantia innominata can be visualized on coronal thin-section T2-weighted MR images. The purpose of this study was to investigate the morphologic changes of the substantia innominata in normal aging by using MR imaging and to determine whether the changes in this structure on MR images were specific to Alzheimer disease (AD). METHODS: The thickness of the substantia innominata was measured on the coronal T2-weighted image obtained through the anterior commissure in 39 healthy control subjects (age range, 25-86 y; mean age, 62 y); 39 patients with AD; and 36 patients with non-AD dementia, including vascular dementia, frontotemporal dementia, and Parkinson disease with dementia. RESULTS: In the control subjects, the thickness of the substantia innominata significantly decreased with age. Compared with age-matched control subjects, both patients with AD and patients with non-AD dementia had significant atrophy of the substantia innominata. The thickness of the substantia innominata significantly correlated with scores from the Mini-Mental State Examination in patients with AD but not in patients with non-AD dementia. CONCLUSION: MR analysis reveals age-related shrinkage of the substantia innominata. Atrophy of the substantia innominata, which reflects degeneration in the nucleus basalis of Meynert, is pronounced both in patients with AD and in those with non-AD dementia. MR imaging features in this structure may not be specific to AD. (+info)