The long-term goal of the application is to understand how the central nervous system (CNS) generates sympathetic tone under basal conditions and formulates complex and highly differentiated cardiovascular response patterns characteristic of such behavioral and pathophysiological states as the defense reaction and neurogenic hypertension.
The specific aims of the application are as follows: 1) To define the connections between four groups of cat medullary neurons believed to comprise the basic circuitry responsible for a major component of basal sympathetic nerve discharge (SND) -- the 2- to 6-Hz rhythm. These are sympathoexcitatory (SE) and sympathoinhibitory (SI) neurons of the lateral tegmental field, SE neurons of the rostral ventrolateral medullary reticular formation (RVLM), and SI neurons of the raphe. 2) To test the hypothesis that the axons of bulbospinal neurons innervating the thoracolumbar intermediolateral nucleus (IML) emit collaterals at cervical levels that engage descending propriospinal systems with sympathetic function. Thus, we envision multisynaptic as well as monosynaptic routes to the IML from the brain stem. 3) To determine whether anatomically established reciprocal pathways between the RVLM, dorsolateral pontine complex and the hypothalamus are involved in modulating activity in the basic medullary circuitry responsibly for the 2- to 6-Hz rhythm in SND. If so, the question whether these loops provide positive and/or negative feedback control of RVLM-SE neurons will be investigated. 4) To test the hypothesis that the basal discharges of any given postganglionic sympathetic nerve in the anesthetized cat are derived from multiple central sources rather than from a single anatomically circumscribed generator. As a corollary, the possibility will be examined that the multiple generators of SND are located at both brain stem and diencephalic levels. 5) To test the hypothesis that the brain stem reticular network governing SND is comprised of distinct modules of synaptically interrelated neurons and that each module has a specific output address (e.g., a particular sympathetic nerve). It is further hypothesized that the selective coupling of modules with different output addresses provides the basis for the differential changes in regional blood flow accompanying such behavioral states as the defense reaction. Thus, we envision the sympathetic network in the reticular formation as a polymorphic or highly plastic system capable of formulating a number of discrete output patterns. The electrophysiological techniques used to study these problems in cats include: antidromic mapping of the axonal projections of single central neurons, autocorrelation, microiontophoresis and microstimulation, post-R wave analysis, power density spectral analysis, spike train analysis, unit spike-triggered averaging of SND and central field potentials, and unit- greater than unit crosscorrelation.
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