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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054194-05
Application #
6184169
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Lathrop, David A
Project Start
1997-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2003-04-30
Support Year
5
Fiscal Year
2001
Total Cost
$215,116
Indirect Cost
Name
Thomas Jefferson University
Department
Pathology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Khan, Rishi L; Vadigepalli, Rajanikanth; McDonald, Mary K et al. (2008) Dynamic transcriptomic response to acute hypertension in the nucleus tractus solitarius. Am J Physiol Regul Integr Comp Physiol 295:R15-27
Zak, Daniel E; Gonye, Gregory E; Schwaber, James S et al. (2003) Importance of input perturbations and stochastic gene expression in the reverse engineering of genetic regulatory networks: insights from an identifiability analysis of an in silico network. Genome Res 13:2396-405
Rector, D M; Rogers, R F; Schwaber, J S et al. (2001) Scattered-light imaging in vivo tracks fast and slow processes of neurophysiological activation. Neuroimage 14:977-94
Rogers, R F; Runyan, J D; Vaidyanathan, A G et al. (2001) Information theoretic analysis of pulmonary stretch receptor spike trains. J Neurophysiol 85:448-61
Paton, J F; Li, Y W; Deuchars, J et al. (2000) Properties of solitary tract neurons receiving inputs from the sub-diaphragmatic vagus nerve. Neuroscience 95:141-53
Paton, J F; Li, Y W; Kasparov, S (1999) Reflex response and convergence of pharyngoesophageal and peripheral chemoreceptors in the nucleus of the solitary tract. Neuroscience 93:143-54
Rector, D M; Rogers, R F; George, J S (1999) A focusing image probe for assessing neural activity in vivo. J Neurosci Methods 91:135-45