Over the past 15 years, experiments on animal models as well as human subjects have demonstrated that the vestibular system contributes to cardiovascular regulation during movement and changes in posture. Accordingly, bilateral labyrinthectomy disrupts an animal's capacity to rapidly adjust blood pressure during postural alterations, although the ability to produce prompt compensatory cardiovascular adjustments recovers over time. During the course of the currently-funded grant we showed that vestibular stimulation produces patterned, specific hemodynamic alterations in particular vascular beds. Furthermore, we uncovered evidence that regions of the caudal vestibular nuclei that influence autonomic regulation integrate a variety of sensory signals reflecting body position in space, and that this multisensory integration may explain why animals lacking vestibular inputs regain the ability to maintain stable blood pressure during postural alterations. These findings gave rise to the following hypothesis: the integration by the central vestibular system of labyrinthine and nonlabyrinthine graviceptive signals leads to complex alterations in regional blood flow that serve to stabilize blood pressure during movement.
Three specific aims are proposed to test this hypothesis. The first specific aim will determine whether bilateral removal of vestibular inputs affects the patterning of hemodynamic responses that ordinarily occur during postural alterations. The second specific aim will explore whether nonlabyrinthine inputs from the limbs and viscera are sufficient to modulate activity of neurons in the autonomic region of the caudal vestibular nuclei, and will ascertain the time course over which nonlabyrinthine signals are substituted for labyrinthine inputs following a bilateral vestibular neurectomy. The third specific aim will determine whether a neuronal substrate is present for limb and visceral inputs to reach a majority of neurons in the caudal vestibular nuclei, and if so will map the neural pathways that relay nonlabyrinthine signals to this region. These experiments will contribute to understanding the mechanisms through which cardiovascular adjustments are made during movement and changes in posture, and may provide insights towards developing therapeutic approaches to alleviate autonomic disturbances in patients with central or peripheral vestibular lesions.
Showing the most recent 10 out of 75 publications
