Neuroscience
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Cation-chloride cotransporters have been considered to play pivotal roles in controlling intracellular and extracellular ionic environments of neurons and hence controlling neuronal function. We investigated the total distributions of K-Cl cotransporter 1 (KCC1), KCC2 (KCC2), and Na-K-2Cl cotransporter 1 (NKCC1) messenger RNAs in the adult rat nervous system using in situ hybridization histochemistry. KCC2 messenger RNA was abundantly expressed in most neurons throughout the nervous system. ⋯ The expression levels of KCC1 and NKCC1 messenger RNAs were relatively low, however, positive neurons were observed in several regions, including the olfactory bulb, hippocampus, and in the granular layer of the cerebellum. In addition, positive signals were seen in the non-neuronal cells, such as choroid plexus epithelial cells, glial cells, and ependymal cells, suggesting that KCC1 and NKCC1 messenger RNAs were widely expressed in both neuronal and non-neuronal cells in the nervous system. These results clearly indicate a wide area- and cell-specific variation of cation chloride cotransporters, emphasizing the central role of anionic homeostasis in neuronal function and communication.
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Hippocampal cholinergic neurostimulating peptide, an undecapeptide originally isolated from the hippocampus of young rats, enhances acetylcholine synthesis in rat medial septal nucleus in vitro. Hippocampal cholinergic neurostimulating peptide is derived from the N-terminal region of its 21-kmol.wt precursor protein. ⋯ Selective inhibition with pharmacological agents revealed that the constitutive hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA level can be up-regulated by D-(-)-2-amino-5-phosphono-valeric acid, and that activity-dependent transcription can be inhibited by tetrodotoxin, nifedipine, 6-cyano-7-nitroquinoxaline-2,3-dione, and scopolamine, but not by mecamylamine. These results indicate that septal cholinergic neurons and hippocampal glutamatergic neurons exert a reciprocal influence over the expression of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA in the hippocampus, and that the activity-dependent and constitutive expressions of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA may be regulated by different routes, involving calcium influx via L-type Ca(2+) channels and N-methyl-D-aspartate receptors.
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Comparative Study
Orphanin FQ produces gender-specific modulation of trigeminal nociception: behavioral and electrophysiological observations.
The present study aimed to determine if orphanin FQ, an endogenous ligand for the opioid receptor like-1 receptor, produces gender-specific effects in the modulation of N-methyl-D-aspartate (NMDA)-evoked responses of trigeminal nociceptive neurons, and in the NMDA-induced nociceptive behavior. Single-unit extracellular recordings were made from nociceptive-specific and wide dynamic range neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized (1.5 g/kg urethane) rats. In the proestrous female, orphanin FQ applied microiontophoretically produced facilitation of the NMDA-evoked responses in 50% (16/32) of nociceptive neurons, inhibition in 31% (10/32), and biphasic effects in 19% (6/32). ⋯ In contrast, in estradiol-treated ovariectomized animals, orphanin FQ facilitated the NMDA-induced scratching behavior by 210%. We conclude from these studies that orphanin FQ is primarily pronociceptive in the female and primarily antinociceptive in the male. Furthermore, we suggest that estrogen is involved in generating the gender-specific effects of orphanin FQ.
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To investigate the basis of the fluctuating activity present in neocortical neurons in vivo, we have combined computational models with whole-cell recordings using the dynamic-clamp technique. A simplified 'point-conductance' model was used to represent the currents generated by thousands of stochastically releasing synapses. Synaptic activity was represented by two independent fast glutamatergic and GABAergic conductances described by stochastic random-walk processes. ⋯ This procedure successfully recreated several properties of neurons intracellularly recorded in vivo, such as a depolarized membrane potential, the presence of high-amplitude membrane potential fluctuations, a low-input resistance and irregular spontaneous firing activity. In addition, the point-conductance model could simulate the enhancement of responsiveness due to background activity. We conclude that many of the characteristics of cortical neurons in vivo can be explained by fast glutamatergic and GABAergic conductances varying stochastically.
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Chronic stress has been shown to induce time-dependent neurodegeneration in the hippocampus, ranging from a reversible damage to a permanent neuronal loss. This damage has been proposed to impair cognitive function in hippocampus-dependent learning tasks. In this study, we have used a 21-day restraint stress procedure in rats, previously reported to induce reversible atrophy of apical dendrites of CA3 pyramidal cells, to assess whether it may influence subsequent performance in the contextual fear conditioning task under experimental conditions involving high stress levels (1 mA shock intensity as the unconditioned stimulus). ⋯ They also showed that chronically stressed rats displayed reduced hippocampal neural cell adhesion molecule, but increased polysialylated expression as well as a trend towards exhibiting increased L1 expression. In summary, these results support the view that a 21-day chronic stress regimen predisposes individuals to develop enhanced contextual fear conditioning responses. They also indicate that cell adhesion molecules might play a role in the structural remodelling that occurs in the hippocampus as a consequence of chronic stress exposure.