Neuroscience
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A neuron's phase response curve (PRC) shows how inputs arriving at different times during the spike cycle differentially affect the timing of subsequent spikes. Using a full morphological model of a globus pallidus (GP) neuron, we previously demonstrated that dendritic conductances shape the PRC in a spike frequency-dependent manner, suggesting different functional roles of perisomatic and distal dendritic synapses in the control of patterned network activity. In the present study we extend this analysis to examine the impact of physiologically realistic high conductance states on somatic and dendritic PRCs and the time course of spike train perturbations. ⋯ Therefore, we analyzed the interactions of PRC stimuli with transient fluctuations in the synaptic background on a trial-by-trial basis. We found that the variability in responses to PRC stimuli and the incidence of stimulus-evoked added or skipped spikes were stimulus-phase-dependent and reflected the profile of the average PRC, suggesting commonality in the underlying mechanisms. Clear differences in the relation between the phase of input and variability of spike response between dendritic and somatic inputs indicate that these regions generally represent distinct dynamical subsystems of synaptic integration with respect to influencing the stability of spike time attractors generated by the overall synaptic conductance.
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The functional role of serotonergic 5-HT(1A) receptors in the modulation of visceral pain is controversial. The objective of this study was to systematically examine the mechanism and site of action of a selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) on visceral pain. In the behavioral model of visceral pain, systemic injection (5-250 μg/kg) of DPAT produced a significant increase in the viscero-motor response (VMR) to colorectal distension (CRD) and this effect was blocked by the selective 5-HT(1A) receptor antagonist WAY-100135 (5 mg/kg, s.c.). ⋯ In electrophysiology experiments, DPAT (50 μg/kg) significantly increased the responses of spinal neurons to CRD, but did not influence the mechanotransduction property of CRD-sensitive pelvic nerve afferent fibers. The effect of DPAT on spinal neurons remained unaffected when tested in spinal-transected (C1-C2) rats. These results indicate that the 5-HT(1A) receptor agonist DPAT produces pronociceptive effects, primarily via the activation of presynaptic 5-HT(1A) receptors in GABAergic neuron to restrict GABA release and thereby disinhibits the excitatory glutamatergic neurons in the spinal cord.
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The central medial nucleus (CM) of thalamus is a prominent cell group of the rostral intralaminar complex of the thalamus. No previous report in the rat has comprehensively described the projections of CM. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we examined the efferent projections of CM, comparing projections from rostral (CMr) and caudal (CMc) regions of CM. ⋯ Main CMc subcortical projection sites were the dorsal striatum and the lateral, central, anterior cortical, and basomedial nuclei of amygdala. The largely complementary output of CMr and CMc to diverse areas of cortex and to regions of the striatum and amygdala suggest a combined CM influence over a widespread area of the anterior cortex and throughout the dorsal and ventral striatum and the amygdala. CM projections to limbic and sensorimotor structures of the rostral forebrain suggest that CM may serve to integrate affective, cognitive and sensorimotor functions for goal-directed behavior.
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Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. ⋯ Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility.
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Previous studies have shown that housing mice with toys and running wheels increases adult hippocampal neurogenesis and enhances performance on the water maze. However, the relative contribution of running versus enrichment to the neurogenic and pro-cognitive effects is not clear. Recently, it was demonstrated that enrichment devoid of running wheels does not significantly enhance adult hippocampal neurogenesis in female C57BL/6J mice. ⋯ The combination of enrichment and running did not significantly increase hippocampal neurogenesis any more than running alone did. Animals in the running-only condition were the only group to show enhanced acquisition on water maze relative to standard cage controls. We confirm and extend the conclusion that environmental enrichment alone does not significantly increase hippocampal neurogenesis or bestow spatial learning benefits in male C57BL/6J mice, even when the modalities of enrichment are very broad.