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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There is evidence for interactions between leptin and cholecystokinin in controlling food intake. Since cholecystokinin acts on vagal afferent neurones, we asked whether the leptin receptor was also expressed by these neurones. Primers for different forms of the leptin receptor were used in reverse transcriptase-polymerase chain reaction (RT-PCR) of rat and human nodose ganglia. ⋯ Immunocytochemical studies revealed leptin-receptor immunoreactivity in neuronal cell bodies. Many neurones co-expressed the leptin and cholecystokinin type A receptors, or leptin receptor and cocaine- and amphetamine-related transcript. We conclude that vagal afferent neurones that express the cholecystokinin type A receptor and cocaine- and amphetamine-related transcript, may also express the long form of the leptin receptor providing a neurochemical basis for observations of interactions between cholecystokinin and leptin.
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Adult rat sensory neurones were maintained in short-term tissue culture and their response to histamine was studied by monitoring changes in intracellular [Ca(2+)] with Fura-2. The proportion of histamine-sensitive neurones increased as the concentration increased from 10 microM to 10 mM. The fraction of responding cells did not change significantly over the first week in culture. ⋯ A combination of U73122 and calcium-free medium abolished all responses to histamine. These data suggest that in addition to activating phospholipase C, high concentrations of histamine gate an influx of calcium that is independent of store depletion. The implications of these results for the transduction of pruritic stimuli is discussed.
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To elucidate the mechanism of orphanin FQ on neuroimmune modulation, the relationship between orphanin FQ and interleukin-1beta in the rat CNS in vivo and in vitro was investigated. In our experiments, it was found that orphanin FQ and interleukin-1beta mRNA transcripts showed a similar distribution in cerebral cortex, hippocampus and hypothalamus. By using the in situ hybridization technique, down-regulation of interleukin-1beta mRNA transcripts by central administration of orphanin FQ was further identified in the traumatic animal model. ⋯ When analyzed by reverse transcription-polymerase chain reaction, interleukin-1beta gene expression was observed to be enhanced and inhibited in primary neuron and microglial cell cultures exposed to orphanin FQ respectively. Interleukin-1beta gene expression in astrocyte cultures was not affected by treatment with orphanin FQ. Our findings suggest that the neuroimmune function of orphanin FQ might be dependent on interleukin-1beta derived from microglia, and the interaction between microglia and neurons.
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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.