The proposed research is a series of anatomical tract tracing studies of the topographical organization of neuronal circuits involving the vestibular nuclei, inferior olive, cerebellar cortex and brain stem autonomic pathways in the rabbit. The research during the previous finding period has analyzed the organization of parallel circuits that process visual and vestibular information for eye movement control. These studies have resulted in an extension of the microcomplex hypothesis for the organization of cerebellar circuits. The proposed studies will test whether this pattern of organization generalizes to regions of the cerebellum and vestibular nuclei that influence the autonomic nervous system. The long-term goal of this project is to identify common neuroanatomical bases for cerebellar contributions to motor control. Specifically, the proposed studies will elucidate neuroanatomical substrates for vegetative signs and symptoms of vestibular dysfunction and motion sickness. The proposed studies will use contemporary multiple anterograde and retrograde tracer technology to examine the organization of vestibular and cerebellar circuits. Double anterograde tracing methods using Phaseolus vulgaris leucoagglutinin (PHA-L) and recombinant tetanus toxin C fragment (rTTC) will be used to identify (1) the topographic organization of vestibular nucleus projections to central sympathetic and parasympathetic pathways and (2) the terminal regions of cerebellar projections to output regions of the vestibular nuclei; transneuronal retrograde transport of rTTC will also be used to verify vestibulo-autonomic and vestibulo-olivary pathways. In other experiments, combined injections of anterograde (Fluoro-Ruby) and retrograde (Fluoro-Gold) fluorescent tracers will be placed (1) in brain stem autonomic regions to identify vestibulo-autonomic output cells, (2) in the vestibular nuclei to simultaneously investigate vestibulo-autonomic, vestibulo-olivary, cerebello-vestibular and olivo-vestibular pathways, (3) in the cerebellar cortex to simultaneously examine the topography of cerebello-vestibular and olivo-cerebellar pathways, and (4) in the inferior olive to simultaneously examine olivo-- vestibular, olivo-cerebellar and vestibulo-olivary topographies. Taken together, these experimental results will (1) directly test whether cerebellar circuits related to both somatic and visceral motor systems have a common modular pattern of organization and (2) elucidate the organization of central vestibular and cerebellar circuits that influence sympathetic, parasympathetic and somatic motor pathways related to visceral function and respiration. In particular, this project has the potential to identify neuroanatomical substrates for the coordination of autonomic and somatic components of responses to vestibular stimulation.
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