The long-term objective of the proposed work is to understand neural mechanisms of cardiovascular control in the baroreceptor vagal reflex. The activation of arterial baroreceptors profoundly affects cardiac function via the vagus nerve. A clinically important role for baroreceptor reflex function is found in hypertension, cardiac insufficiency and arrhythmias. However, the cellular basis of the central neuronal components, and thus the regulatory function, of this homeostatic system are poorly understood. For example, single baroreceptive nucleus tractus solitarius (NTS) neurons do not obviously reproduce the afferent input pattern and have non-linear responses to changes in arterial pressure. At present it is not clear what features of arterial pressure are represented in the activity of neurons in the NTS, nor is it clear by what neuronal processing mechanisms sensory representation is achieved. The proposed work will focus on the processing by second- and higher-order NTS neurons that receive and process these inputs. The project will perform in vivo recording from NTS neurons under conditions of precise computer-controlled patterns of baroreceptor stimulation and detailed nonlinear analysis of neuronal response that will describe the processing by these neurons in reflex function. These studies ask (1) are """"""""extinciton"""""""" responses typical of NTS barosensitive neurons? (2) do NTS neurons display consistent pressure receptive field properties? (3) How is mean pressure encoded by barosensitive NTS neurons? (4) What do """"""""silent"""""""" NTS barosensitive neurons encode from the pressure? and (5) How is the pressure encoded by """"""""higher-order"""""""" NTS barosensitive neurons? These studies should significantly clarify baroreflex function and the basis, in the synaptic connections central neurons, for mechanisms of cardiovascular regulation. The results will contribute to a foundation for diagnostic and therapeutic approaches to cardiac arrhythmias, cardiac insufficiency and hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Thomas Jefferson University
Schools of Medicine
United States
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