Browsing School, Graduate by Subject "Vagus Nerve"
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Calcium(2+) physiology in primary vagal sensory neuronsMicrofluorimetric, electrophysiological, pharmacological, and intracellular photorelease techniques were used to study Ca2+ physiology in rabbit vagal sensory neurons (nodose ganglion neurons, NGNs). NGNs exhibit robust Ca2+-induced Ca2+ release (CICR) that can be triggered by caffeine, the classic CICR agonist. A caffeine-induced increase in cytosolic free Ca2+ concentration ([Ca2+ ]i) was traditionally taken as diagnostic of the existence of CICR. However, when CICR was disabled through depletion of intracellular Ca2+ stores or pharmacological blockade of intracellular Ca 2+ release channels (ryanodine receptors, RyRs), caffeine still elicited a significant rise in [Ca2+]i in ∼50% of NGNs. We demonstrated that this rise in [Ca2+]i results from Ca2+ influx, and that Ca2+ influx is one component of a non-selective cation current that is activated by caffeine. Therefore, in approximately half of all NGNs, caffeine elicits both CICR and Ca2+ influx. We determined that d-myo-inositol 1,4,5-trisphosphate receptors (IP3Rs), another type of intracellular Ca2+ release channel, coexist with RyRs in NGNs. ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in [Ca 2+]i (Ca2+ transients) that have a dual origin: (1) Ca2+ influx via P2X receptors and voltage-gated Ca2+ channels; and (2) intracellular Ca2+ release, via IP3Rs and RyRs, that requires activation of P2Y receptors and phospholipase C. We determined that Ca2+ transients evoked by IP3 photorelease can gate a Ca2+-activated K+ current (I IP3) in NGNs. IIP3 is unaffected by three common antagonists of Ca2+-activated K+ currents: iberiotoxin, apamin, and 8-Br-CAMP. Using caffeine to selectively deplete intracellular Ca2+ stores, we show that while CICR does not contribute significantly to global IP3-evoked Ca2+ transients, surprisingly, ∼20% of IIP3 is activated by CICR. We propose a model of Ca2+ signaling microdomains that rationalize these observations. We showed that ATP can evoke a Ca2+-activated K + current in 57% of NGNs. ATP-evoked Ca2+ influx activates ∼75% of this current, while ATP-evoked intracellular Ca2+ release activates the other ∼25%. We also determined that NGNs express P2X receptors that mediate robust influx, therefore our data suggest that ATP can exert both excitatory and inhibitory effects in NGNs.
Silencing the vagus nerve produces homeostatic changes at second order nucleus tractus solitarius synapsesMany diseases, pathologies and medical treatments alter vagal nerve activity, but the underlying central nervous system changes caused by these treatments are not well understood. My study was designed to test how silencing action potential activity in the vagus nerve of rats affects synaptic plasticity at second order nucleus tractus solitarius (NTS) synapses. At least seven days following unilateral vagotomy, in vitro horizontal brainstem slices containing the NTS were prepared for whole cell patch clamp recording. Vagotomy caused a homeostatic increase in evoked excitatory postsynaptic current (evEPSC) amplitudes and a decrease in the frequency of spontaneous EPSCs (spEPSCs). These results were dramatically altered by including the GABAA receptor antagonist, bicuculline (BIC), in the recording bath. In order to test whether the results observed following vagotomy were due to the loss of impulse activity, rather than the influence of inflammatory or other injury-induced factors, I implanted rats for six to eight days with a cuff containing the sodium channel blocker tetrodotoxin (TTX). After six to eight days, I removed the brainstem and prepared in vitro horizontal NTS slices. Similar to vagotomy, TTX treatment caused a homeostatic increase in evEPSC amplitudes and a decrease in the frequency of spEPSCs. No alterations to passive or active postsynaptic membrane properties following TTX treatment or vagotomy observed, nor were spEPSC amplitudes changed. These results suggest that silencing vagal impulse activity causes a homeostatic increase in synaptic efficacy at monosynaptic NTS synapses.