Visceral sensory pathways that innervate the cardiovascular, respiratory and gastrointestinal systems are critical for reflex control of autonomic homeostasis. It is well established that functional characteristics of visceral reflexes, including arterial baro- and chemoreflexes, changes dramatically during perinatal development. However, the cellular mechanisms underlying the functional maturation of visceral reflexes are largely unknown. The leading hypothesis of this proposal is that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF), released from the central terminals of visceral sensory afferents, regulates the activity-dependent maturation of postsynaptic target neurons. This hypothesis, supported by our recently published data and preliminary studies, will be tested using nodose ganglion primary and second-order sensory neurons, as well as functionally homogenous primary and second-order neurons in the aortic baroreceptor pathway, as a model. The proposed studies will utilize several innovative techniques, uniquely suited for studies of this kind, to characterize: 1) developmental regulation of activity-dependent expression of BDNF in nodose ganglion primary sensory neurons in general, and baroreceptor afferents in particular, and 2) electrophysiological and morphological effects of BDNF on second-order sensory neurons, including baroreceptor-relay neurons, from the developing nucleus tractus solitarius (NTS). A novel combination of electrical field stimulation with a highly sensitive, modified ELISA in situ, will be used to characterize changes in BDNF protein content in response to patterns of stimulation that mimic the physiological activity of baroreceptor afferents. Revealing the cellular mechanisms of BDNF regulation in visceral primary sensory neurons is a key to understanding BDNF role in visceral sensory pathways. A second part of the proposed work will analyze BDNF effects on voltage-activated potassium currents and dendritic morphology in specifically identified postsynaptic targets of BDNF-containing visceral sensory neurons and baroreceptor afferents. Results of these studies will provide new information fundamental to our understanding of basic mechanisms that govern development of sensory pathways. Moreover, by using the arterial baroreceptor pathway as a model, the proposed studies are relevant to understanding pathogenesis of developmental disorders of the cardio-respiratory system, such as Sudden Infant Death Syndrome (SIDS). ? ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CICS (01))
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Thrasher, Terry N
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Oregon Health and Science University
Schools of Dentistry
United States
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