Multisensory control of autonomic function

 描述(由申请人提供)：两种反馈机制，前庭交感神经反射和压力感受器反射，并行作用，在姿势变化时维持稳定的血压。此外，运动规划涉及前馈自主反应，以确保在运动过程中身体有足够的血液供应。然而，反馈和前馈信号对控制自主神经功能的脑干神经元活动的交互作用知之甚少。这项授权使用了清醒动物的神经生理记录，来自调节血压的脑干神经元，并研究了关于前庭交感神经和压力感受器反射的综合控制的三个新概念。首先，这些响应的增益根据即将到来的头朝上倾斜的预期幅度进行认知调整。其次，双侧迷路切除后压力感受器反射的增益增加，以补偿前庭交感反应的损失。第三，前庭交感反射和压力感受器反射的增益都是通过悬垂的输入来调节的，悬垂是小脑尾部蚯蚓的一个区域。特别是，我们将确定悬垂浦肯野细胞是否介导了与认知相关的前庭交感神经和压力感受器反射增益的变化，以及当血压在体位变化期间变得不稳定时压力感受器反射的可塑性变化。这些实验具有临床意义。这项工作将确定对姿势变化的预期是否会导致血管阻力的前馈变化，从而在随后的运动中防止外周血液聚集和立位性低血压，以及小脑虱子是否介导了这些反应。随着年龄的增长，直立性低血压变得更加普遍，这也与小脑变性有关。与衰老相关的小脑退行性变可能导致心血管疾病，通常导致摔倒和受伤，这一概念以前从未被考虑过。这些研究的发现也适用于认知影响血压的其他临床疾病，包括焦虑和应激障碍。

 DESCRIPTION (provided by applicant): 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.