Cranial afferent neurons are the first step in medullary reflex pathways and synapse at the nucleus of the solitary tract (NTS). Reflex control produced as a result of medullary reflex pathways is important in the regulation of many physiological parameters including cardiovascular function. The paraventricular nucleus (PVN) of the hypothalamus helps to coordinate these reflex functions through peptidergic projections to the NTS. Two prototypic neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), are synthesized in the PVN and contained in axons terminating within NTS. Studies of cardiovascular regulation suggest that AVP and OT are released in NTS under certain physiological conditions and alter the baroreceptor reflex. OT acting in NTS slows the heart and decreases arterial pressure, an action consistent with an enhancement of the baroreflex;the mechanisms of these effects, however, remain unknown. My global hypothesis is that oxytocin enhances the baroreflex by facilitating baroreceptor afferent synaptic transmission within NTS. This proposal will test whether oxytocin enhances cranial visceral afferent / NTS synaptic transmission using a combination of anatomical and electrophysiological approaches. I will use an in vitro medullary brain slice, which contains the solitary tract and the NTS, with patch-clamp recording techniques to measure electrical current and synaptic transmission within a single NTS neuron. Localized electrical stimulation of the solitary tract produces synaptic responses in NTS neurons that are used to identify second order (direct) synaptic connections. I will also investigate a specific medullary reflex pathway important in the control of cardiovascular function. Specifically, I will test if oxytocin enhances synaptic transmission to NTS neurons receiving baroreceptive afferent inputs and projecting to the caudal ventro-lateral medulla (CVLM). The Identification of baroreceptive afferent populations and NTS neurons with projections to the CVLM will be accomplished using fluorescent neuronal tracers. The combination of anatomic tracing combined with whole cell electrophysiological techniques will allow for the test of the following specific hypotheses:
Aim 1) Does oxytocin enhance afferent glutamatergic transmission to second-order NTS neurons? Aim 2) Does oxytocin enhance synaptic transmission to baroreceptive second-order NTS neurons? Aim 3) Does oxytocin enhance ST transmission to the caudal ventrolateral medulla? This research will expand our understanding of autonomic reflex control, how the cardiovascular system is regulated and may suggest sites for therapuetic intervention and treatment of cardiovascular disease.
