Neural reflexes rapidly adjust the cardiovascular system yet little is established about mechanisms governing their central nervous system pathways. The initial neurons are located within nucleus tractus solitarius (NTS). NTS integrates primary afferent information with CNS inputs. Our Research Plan will provide a cellular understanding of NTS integration and autonomic control. Heterogeneity in neuronal phenotype and pathway may reflect inherent patterns of specificity and, ultimately, represent therapeutic opportunities. Our Research Plan will address questions regarding heterogeneity of cellular properties as well as pathways of network organization within and beyond NTS. Our approach capitalizes on knowledge of cranial sensory neurons to probe the identity of NTS neurons. Our major long-term goal tests the hypothesis that sensory synapses within NTS are sites of major transformation of information. Our work features a cellular electrophysiological approach to NTS utilizing unique in vitro preparations of brain stem slices and dissociated cells. This renewal proposal focuses on synaptic processing (pre- and postsynaptic) as well as defining particular pathways and subsets of NTS neurons. The combination of molecular/cellular phenotype together with pathway information will allow us to define the roles of particular neurons within pathways. In brain stem slices and dissociated neurons with intact native boutons, we use live cell imaging, electrophysiology including paired recordings, plus retro- and anterograde labeling. We will target key areas in NTS sensory processing: presynaptic mechanisms regulating transmitter release, transmitter interactions, and potassium channels.
Our Aims focus on GABAb receptors at 2nd order NTS neurons, regulation of GABAergic NTS neurons, cell-cell coupling, mechanisms of vasopressin action, and PVN and CVLM-projecting neurons.
These Aims will provide new and direct information about NTS that leads to a better understanding of the normal basis of the neural control of the circulation as pathophysiology.
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