Neuroscience
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Comparative Study
Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability.
Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. ⋯ Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.
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Administration of typical and atypical antipsychotic drugs leads to activation of cells in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus, implicating important shared effects of these drugs. However, the exact cell types responding to antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus are unclear. ⋯ The present study provides pharmacological evidence, at the cellular level in vivo, that the shared effects of antipsychotic drugs, whether typical and atypical, is activation of dynorphinergic GABA neurons in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus. Alternative ways to modulate dynorphinergic GABA neuronal activity or its target receptors might present an important new avenue for the treatment of schizophrenia and other psychotic disorders.
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Comparative Study
Stimulant doses of caffeine induce c-FOS activation in orexin/hypocretin-containing neurons in rat.
Although caffeine is a commonly used CNS stimulant, neuronal mechanisms underlying its stimulatory effect are not fully understood. Orexin (hypocretin)-containing neurons play a critical role in arousal and might be activated by acute administration of caffeine. We examined this possibility by using dual-immunostaining for orexin B and c-Fos protein as a marker for neuronal activation. ⋯ In contrast, caffeine significantly increased the number of non-orexin-immunoreactive neurons expressing c-Fos only in the dorsomedial nucleus. These results indicate that systemically administered caffeine preferentially activates orexin neurons over non-orexin neurons in the same field, and that this activation is most pronounced in the perifornical region where orexin neurons are most concentrated. The activation of orexin neurons might play a role in the behavioural activation by caffeine.
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The cortical information flow via the perforant path represents a major excitatory projection to the hippocampus. Lesioning this projection leads to massive degeneration and subsequently to reorganization in its termination zones as well as in primary non-affected subfields of the hippocampus. The molecular mechanisms and factors which are involved in the postlesional events are poorly defined. ⋯ In the hippocampus, the control level was reached again at 21 dal, whereas the cortex reached the control level at 10 dal. In comparison, the mRNA transcripts of the receptors CCK(A) and CCK(B) remained unchanged. Since CCK-containing neurons are involved in the modulation of pyramidal and granule cell excitability, our data indicate a time course correlation between CCK mRNA expression and postlesional axonal sprouting response in the hippocampus.
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Comparative Study
Estradiol inhibits atp-induced intracellular calcium concentration increase in dorsal root ganglia neurons.
Estrogen has been implicated in modulation of pain processing. Although this modulation occurs within the CNS, estrogen may also act on primary afferent neurons whose cell bodies are located within the dorsal root ganglia (DRG). Primary cultures of rat DRG neurons were loaded with Fura-2 and tested for ATP-induced changes in intracellular calcium concentration ([Ca(2+)](i)) by fluorescent ratio imaging. ⋯ Co-administration of these blockers with estrogen induced a further decrease of the ATP-induced [Ca(2+)](i) flux. Together, these results suggest that although ATP stimulation of P2X receptors activates L-, N-, and P-type VGCC, estradiol primarily blocks L-type VGCC. The estradiol regulation of this ATP-induced [Ca(2+)](i) transients suggests a mechanism through which estradiol may modulate nociceptive signaling in the peripheral nervous system.