Vanilloid type-1 receptors (VR1) are abundant in the dorsal vagal complex, where their function is mostly unknown. We examined the role of VR1 in regulating synaptic inputs to neurons of the dorsal motor nucleus of the vagus (DMV). Using patch-clamp recordings from DMV neurons in brainstem slices, capsaicin was found to increase action potential-independent inhibitory input onto DMV neurons. This rapid effect was mimicked by application of the endogenous cannabinoid, anandamide and blocked by VR1 antagonists. The VR1-mediated facilitation of synaptic inhibition was reduced by ionotropic and metabotropic glutamate receptor antagonists, suggesting an indirect, heterosynaptic enhancement of GABA release caused by a VR1-mediated increase in glutamate release from presynaptic terminals of excitatory neurons. Application of L-glutamate also increased GABA release. The paired-pulse ratio was increased for IPSCs evoked after electrical stimulation of the nucleus tractus solitarius, but the effect was slower than for the enhancement of spontaneous and miniature IPSCs. Capsaicin also increased the frequency of glutamatergic postsynaptic currents in a VR1-mediated manner. Results of these studies suggest that VR1-containing glutamatergic terminals contact DMV neurons. Activation of VR1 potently enhances glutamate release onto GABAergic terminals, facilitating GABA release. Endogenous cannabinoids can thereby rapidly enhance inhibitory input to DMV neurons via VR1-mediated presynaptic mechanisms.
We have developed a novel technique to measure gastric volume in vivo in mice; this will be invaluable for revealing gastric alterations in genetically modified mice models, thus expanding our understanding of the mechanisms underlying functional disorders. Experimental data on gastric tone currently available has focused on rats using isovolumetric techniques to measure pressure changes, whereas clinical studies use barostatic techniques to measure volume changes. For better translational approaches, we assessed the feasibility of using a miniaturized barostat to measure gastric volume changes in urethane-anaesthetized and unanaesthetized-decerebrate mice. Additionally, we assessed whether central vagal stimulation alters gastric volume in urethane-anaesthetized mice. Nitric oxide donor sodium nitroprusside (1mg kg-1 i.p.) increased gastric volume (+134 +/- 20 microL), whereas the cholinergic agonist carbachol (3 microg kg-1 i.p.) decreased gastric volume (-153 +/- 20 microL). Similar responses were obtained in urethane-anaesthetized and unanaesthetized-decerebrate animals. Microinjection of L-glutamate (25 nmol) into dorsal motor nucleus of the vagus (DMV) altered gastric volume; microinjection into rostral DMV led to gastric contraction (-83 +/- 18 microL) while stimulation of caudal DMV resulted in gastric relaxation (+95 +/- 16 microL). This reveals a functional organization of DMV in mice. This study validates barostatic techniques for application to mice. An understanding of gastric contractility and tone is clinically relevant as impaired gastric accommodation reflex may be an underlying cause of functional dyspepsia.
VDT work consists of static muscle activity in the arms, neck, shoulders and back to keep the head and hands in a mostly fixed working position. The aim of this study was to investigate alternative VDT workstation configurations that may reduce the muscle force of these static contractions by providing support to the head/neck, arm and back regions of the body. Effects of an inclined chair back with headrest and a chair mounted split keyboard (CMSK) were investigated. For a typing task, combining a CMSK with the headrest and inclined chair back resulted in significantly lower muscle activity in the neck (>35% reduction) and shoulders (>64% reduction), compared to utilizing a straight keyboard in a more upright posture without a headrest. No significant difference in typing accuracy existed between the configurations; however, productivity was reduced with the CMSK. Potential applications for alternative VDT work postures are discussed.
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