Neuroscience
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Substance P (SP) regulates inhibitory synaptic transmission mediated by GABAA receptors in the cerebral cortex; however, SP-mediated regulation of excitatory synaptic transmission remains poorly understood. We performed whole-cell patch-clamp recordings from pyramidal neurons to examine the effects of SP on excitatory postsynaptic currents (EPSCs) mediated via AMPA receptors in the insular cortex (IC), which is involved in nociceptive information processing. First, EPSCs evoked by minimal electrical stimulation (eEPSCs) including stepwise EPSCs and failure events, were examined. ⋯ NO imaging using the fluorescent probe DAX-J2 Red supports this hypothesis: SP increased the fluorescence intensity of DAX-J2 Red in some GABAergic neurons. Furthermore, both L-NAME, an NOS inhibitor, and PTIO, an NO scavenger, diminished the SP-induced suppression of eEPSCs. These results suggest that the activation of presynaptic NK1 receptors contributes to SP-induced eEPSC suppression by activating the NO synthesis pathway in GABAergic neurons. (246 words).
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Chronic intermittent ethanol (CIE) exposure dysregulates glutamatergic and GABAergic neurotransmission, facilitating basolateral amygdala (BLA) pyramidal neuron hyperexcitability and the expression of anxiety during withdrawal. It is unknown whether ethanol-induced alterations in nucleus basalis magnocellularis (NBM) cholinergic projections to the BLA mediate anxiety-related behaviors through direct modulation of GABA and glutamate afferents. Following 10 days of CIE exposure and 24 h of withdrawal, we recorded GABAergic and glutamatergic synaptic responses in BLA pyramidal neurons with electrophysiology, assessed total protein expression of cholinergic markers, and quantified acetylcholine and choline concentrations using a colorimetric assay. ⋯ CIE caused a three-fold increase in BLA acetylcholine concentration, with no changes in α7 nAChR or cholinergic marker expression. These data illustrate that α7 nAChR-dependent changes in presynaptic function serve as a proxy for CIE-dependent alterations in synaptic acetylcholine levels. Thus, cholinergic projections appear to mediate CIE-induced alterations at GABA/glutamate inputs.
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The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. ⋯ Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway.
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Demyelination is a well-known pathological process in CNS disorders such as multiple sclerosis (MS). It provokes progressive axonal degeneration and functional impairments and no efficient therapy is presently available to combat such insults. Recently, we have shown that etazolate, a pyrazolopyridine compound and an α-secretase activator, was able to promote myelin protection and remyelination after cuprizone (CPZ)-induced acute demyelination in C57Bl/6 mice. ⋯ Spatial memory evaluated was not affected either by CPZ intake or etazolate treatment in both protocols. Altogether, this study shows that the beneficial effect of etazolate upon demyelination does not occur at the gene expression level at the time points studied. Furthermore, our results also highlight the difficulty in revealing functional sequelae following CPZ intoxication.
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Astrocytes are now known to play crucial roles in the central nervous system, supporting and closely interacting with neurons and therefore able to modulate brain function. Both human postmortem studies in brain samples from patients diagnosed with Major Depressive Disorder and from animal models of depression reported numerical and morphological astrocytic changes specifically in the hippocampus. In particular, these studies revealed significant reductions in glial cell density denoted by a decreased number of S100B-positive cells and a decrease in GFAP expression in several brain regions including the hippocampus. ⋯ Both antidepressants decreased astrocytic complexity immediately after stress exposure. Moreover, we show that astrocytic alterations, particularly an increased number of S100B-positive cells, are observed after recurrent stress exposure. Interestingly, these alterations were prevented at the long-term by either fluoxetine or imipramine treatment.