Research over the past decade has demonstrated that the vestibular system influences the control of blood pressure, both in humans and in animal models. The effects of the vestibular system on cardiovascular control are mainly mediated through the sympathetic division of the autonomic nervous system. Peripheral vestibular lesions have been shown to diminish the capability to rapidly and accurately make necessary cardiovascular adjustments during changes in posture. Thus, one role of vestibulo-cardiovascular influences appears to be eliciting changes in blood distribution in the body so that stable blood pressure is maintained during movement. However, deficits in correcting blood pressure following vestibular lesions diminish over time, and are less severe when non-labyrinthine sensory cues regarding body position in space are provided; these observations show that pathways that mediate vestibulo-sympathetic reflexes are subject to plasticity. The focus of the current grant is to explore the adaptive plasticity in cardiovascular responses elicited by the central vestibular system. In particular, the role that the cerebellum may play in adaptation of these responses will be examined, as well as the possibility that nonlabyrinthine inputs to the central vestibular system may be important in controlling blood pressure during movement.
Three specific aims are proposed in the current application. In the first aim, the role of the posterior cerebellar vermis in modulating vestibulo-cardiovascular responses will be explored. This region of the vestibulo-cerebellum, which includes the uvula and parts of the nodulus, has been shown in numerous studies to participate in the regulation of blood pressure. Because this cerebellar region has extensive projections to areas of the vestibular nuclei that mediate vestibulo-sympathetic responses and is known to participate in plastic changes in vestibulo-ocular reflexes, it seems likely that the uvula and nodulus modulate vestibular influences on cardiovascular regulation. The second specific aim will determine the sources of non-labyrinthine inputs to the vestibular nuclei, and will explore the role of these signals in modulating activity of vestibular nucleus neurons following vestibular lesions. The third specific aim will determine whether nonlabyrinthine inputs to the vestibular nuclei have the capacity to elicit compensatory blood pressure changes during body rotations. By understanding the mechanisms through which cardiovascular adjustments are made during movement and changes in posture, therapeutic strategies may be developed to alleviate autonomic problems in patients with central or peripheral vestibular lesions and in astronauts, who are known to suffer from postural-related hypotension following spaceflight.
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