Two feedback mechanisms, vestibulosympathetic and baroreceptor reflexes, act in parallel to sustain stable blood pressure during changes in posture. In addition, motor planning engages feedforward autonomic responses that assure an adequate blood supply to the body during movement. However, little is known about the interactive effects of feedback and feedforward signals on the activity of brainstem neurons that control autonomic function. This grant employs neurophysiological recordings in conscious animals from brainstem neurons that regulate blood pressure, and investigates three novel concepts regarding the integrated control of vestibulosympathetic and baroreceptor reflexes. First, the gain of these responses is adjusted cognitively in accordance with the expected magnitude of an upcoming head-up tilt. Second, the gain of baroreceptor reflexes increases following a bilateral labyrinthectomy to compensate for the loss of vestibulosympathetic responses. Third, the gains of both vestibulosympathetic and baroreceptor reflexes are adjusted through inputs from the uvula, a region of the caudal cerebellar vermis. In particular, we will determine whether uvula Purkinje cells mediate cognition-related changes in the gains of vestibulosympathetic and baroreceptor reflexes, as well as plastic changes in baroreceptor reflexes when blood pressure becomes labile during postural alterations. These experiments have clinical implications. This work will ascertain whether anticipation of postural changes causes feedforward alterations in vascular resistance that prevent peripheral blood pooling and orthostatic hypotension during the ensuing movement, and whether the cerebellar vermis mediates these responses. Orthostatic hypotension becomes more prevalent during aging, which is also associated with cerebellar degeneration. The notion that aging-related cerebellar degeneration could lead to a cardiovascular disturbance that commonly results in falling and injuries has not been previously considered. The findings from these studies also have implications for other clinical conditions where cognition affects blood pressure, including anxiety and stress disorders.
The proposed experiments will contribute to understanding the mechanisms by 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. In addition, they are likely to provide key general insights into neural regulation of blood pressure, which could be important in devising treatments for autonomic dysfunction.
| Patel, Neesirg M; Baker, Ethan A G; Wittman, Samuel R et al. (2018) Cardiovascular adjustments during anticipated postural changes. Physiol Rep 6: |
| Barman, Susan M; Yates, Bill J (2017) Deciphering the Neural Control of Sympathetic Nerve Activity: Status Report and Directions for Future Research. Front Neurosci 11:730 |
| Balaban, Carey D; Yates, Bill J (2017) What is nausea? A historical analysis of changing views. Auton Neurosci 202:5-17 |
| McCall, Andrew A; Miller, Derek M; Yates, Bill J (2017) Descending Influences on Vestibulospinal and Vestibulosympathetic Reflexes. Front Neurol 8:112 |
