Circuitry for specific vestibulo-ocular and vestibulo-spinal reflexes contains two components: a brain stem circuit that involves vestibular nuclei and a cerebellar microzone that can modulate activity in the brain stem circuit. The proposed research continues tests of the hypothesis that vestibulo-autonomic pathways show an analogous pattern of organization. Studies during the previous funding period have identified both ascending vestibulo-parabrachial and descending vestibulo-autonomic pathways that originate in the brain stem vestibular nuclei, and a cerebellar contribution to these vestibular nucleus regions that originates from the lateral nodulus-ventral uvula. Since the descending pathway provides a direct link with autonomic reflex pathways, while the ascending pathway is linked to limbic and prefrontal circuits, these connections may contribute to the autonomic and affective signs of both vestibular dysfunction and motion sickness. The proposed studies will test the hypotheses that: (1) The ascending and descending components of caudal medial vestibular nucleus and inferior vestibular nucleus projections to autonomic circuits originate from different populations of neurons. (2) The projections from the parabrachial complex to the vestibular nuclei are reciprocal to vestibuloparabrachial connections. (3) Serotonergic innervation of the vestibular nuclei is regionally selective and 5-HT2A and 5-HT2C receptors are expressed by vestibular nucleus neurons that project to the parabrachial nucleus. (4) Stimulation of the rostral (superior and rostral medial) and caudal (inferior and caudal medial) vestibular nuclei produces different autonomic responses. (5) Specific sagittal groups of Purkinje cells (zones) in the anterior lobe cerebellar autonomic regions connected differentially with the inferior olive, vestibular nuclei and parabrachial nuclei. (6) The autonomic effects of anterior lobe stimulation are mediated through connections with the vestibular nuclear autonomic regions.
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