verbatim): The autonomic nervous system contributes importantly to the homeostatic regulation of the heart and blood vessels through arterial baroreflexes and yet our understanding of the central nervous system mechanisms is limited. The sensory synapse of baroreceptors in the nucleus tractus solitarius (NTS) is unique since its participation is obligatory in the baroreflex. Our Research Plan targets this synapse to provide greater understanding of the cellular mechanisms at the earliest stages of the baroreflex. To best approach the cellular mechanisms operating in NTS, we have developed unique in vitro approaches incorporating dye labeling of aortic baroreceptors together with imaging and intracellular electrophysiology to assay synaptic transmission at single neurons under controlled conditions. Our new technical approach allows us to visualize and patch record from NTS neurons with. fluorescently labeled aortic baroreceptor boutons. Isolated, dispersed NTS neurons with attached sensory synaptic boutons will be studied to isolate ionic currents and signal transduction mechanisms in parallel experiments. The major long term goal is to test the hypothesis that this sensory synapse within NTS is the site of major transformation of sensory information. This work will focus on the synapse (pre- and postsynaptic elements) as well as potassium currents of the postsynaptic NTS neurons.
Aims will examine the role of non-glutamatergic mediators in frequency dependent sensory synaptic depression, the presynaptic mechanisms modulating transmitter release, glutamate and GABA receptor interactions, potassium channels as a modulation target, and local inhibitory feedback interactions within NTS. Together, these Aims will provide new and direct information about the mechanisms of central nervous system integration and information processing of arterial baroreceptors at first stage of cardiovascular regulation.
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