VESTIBULO-CEREBELLAR CIRCUITS

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The primary goal of this subproject is to provide detailed characterization of the anatomical organization of the vestibulo-autonomic system. The study is divided into two related, but separate sets of experiments. First, these investigators have previously shown that neurons in the caudal medial vestibular and inferior vestibular nuclei have both descending projections to autonomic regions and ascending projections to portions of the parabrachial nuclei that are associated with autonomic function. Similar ascending projections to the parabrachial nuclei arise from the more rostral region of the superior vestibular nucleus. The first specific aim will address the issue of whether separate or collateral neuronal populations in the vestibular nuclei give rise to the ascending and descending projections by injections of two different fluorescent tracers in each animal The regional distribution of labeled vestibular nuclei neurons, as well as the presence of absence of double labeled cells will be determined. The second aim will determine whether the parabrachial regions form reciprocal connections with the vestibular nuclei, again by using multiple anterograde and retrograde tracers placed in different regions. The third aim addresses the issue of which population of vestibular nuclei neurons is responsible for specific autonomic reflexes, such as modulation of heart rate, blood pressure, and respiration. Discrete injections of glutamate into different nuclear regions will be made while monitoring autonomic reflexes. The second set of experiments seeks to determine the existence and organization of cerebellar microcomplexes that are associated with vestibulo-autonomic function. The fourth specific aim will determine if autonomic related regions of the vestibular nuclei receive inputs from specific sagittal zones of the cerebellum anterior lobe and inputs from the inferior olive. In some experiments, both anterograde and retrograde tracers will be injected into different cerebellar regions, with terminal projections in the vestibular nuclei and labeled neurons in the inferior olive noted. In other experiments, regions of the cerebellum and vestibular nuclei will be examined following anterograde tracers placed in the inferior olive. Results from the two sets of experiments will be compared and mapped for regional topography. The fifth specific aim will address whether the cerebellar and vestibular nuclei regions organized into microcomplexes as determined in aim 4 are involved in blood pressure modulation. Electrical stimulation of cerebellar regions will be performed while monitoring autonomic reflexes, then vestibular nuclei regions will be blocked by bicuculline and the elicited reflexes re-examined.