Neuroscience
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The amygdala plays an important role in the interpretation of emotionally significant stimuli and has strong projections to brainstem regions regulating muscle tone and sleep. Cataplexy, a symptom of narcolepsy, is a loss of muscle tone usually triggered by sudden, strong emotions. Extracellular single-unit recordings were carried out in the amygdala of narcoleptic dogs to test the hypothesis that abnormal activity of a subpopulation of amygdala neurons is linked to cataplexy. ⋯ We hypothesize that these cell populations have a role in mediation or modulation of cataplexy through interactions with meso-pontine regions controlling atonia. The anticholinesterase physostigmine, at doses which increased cataplexy, did not alter the activity of the cataplexy-related cells or of other amygdala cells, suggesting that its effect on cataplexy is mediated 'downstream' of the amygdala. The alpha-1 blocker prazosin, at doses which increased cataplexy, increased discharge in a subgroup of the cataplexy active cells and in a number of other amygdala cells, indicating that prazosin may modulate cataplexy by its action on amygdala cells or their afferents.
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Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. ⋯ It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co-stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex.
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Galanin immunoreactive fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease, perhaps exacerbating the cholinergic deficit. The purpose of our study is to determine whether a similar phenomenon occurs following intraparenchymal injection of 192 IgG-saporin, a specific cholinergic neurotoxin, within the nucleus of the horizontal limb of the diagonal band of Broca. Immunotoxic lesion produced on average a 31% reduction in cholinergic cell counts ipsilateral to the lesion, compared to the contralateral side. ⋯ There was no statistically significant correlation between the extent of cholinergic cell loss and the increase in galanin immunoreactivity surrounding the lesion. Yet, since both of these changes persist over time, we suggest that galanin plasticity is triggered by neuronal damage. Our model can be useful to test the role that galanin plays in the regulation of acetylcholine and the efficacy of galanin inhibitors as potential therapeutic interventions in Alzheimer's disease.
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Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice.
Somatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. ⋯ Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning.
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Synapse formation in CNS neurons requires appropriate sorting and clustering of neurotransmitter receptors and associated proteins at postsynaptic sites. In GABAergic synapses, clustering of GABA(A) receptors requires gephyrin, but it is not known whether presynaptic signals are also involved in this process. To investigate this issue, we analyzed the subcellular distribution of GABA(A) receptors and gephyrin in primary cultures of cerebellar granule cells, by comparing cells receiving GABAergic input with cells devoid of such afferents. ⋯ To determine whether signaling mediated by GABA(A) receptors is required for the formation of appropriately matched gephyrin clusters, cultures were treated chronically with bicuculline, or with either muscimol or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. All these treatments failed to influence the distribution of gephyrin clusters. We conclude that although GABAergic presynaptic terminals have a preponderant influence on the distribution of gephyrin clusters in dendrites of cerebellar granule cells, GABA transmission is dispensable for postsynaptic clustering of gephyrin and GABA(A) receptors and for the formation of appropriately matched GABAergic synapses.