Vestibular Regulation of Respiratory Muscle Activity

描述(申请人提供)：各种实验方法已经证实，前庭系统有助于调节胸腔和腹部呼吸泵肌肉的活动，以及调节运动和姿势变化期间上呼吸道阻力的肌肉。然而，这些影响是复杂的，以至于前庭系统在调节空气进出肺的运动方面的生理作用尚不清楚。当前提案的具体目标1将通过检查双侧迷路切除对吸气和呼气期间交换的空气的压力、体积和流速的影响来确定这一角色，因为身体相对于重力的方向发生了变化。先前的实验也表明，一些将前庭信号传递给呼吸运动神经元的神经元位于延髓内侧网状结构，但这些细胞不足以产生前庭-呼吸反应。我们的解剖学研究和其他人的生理学研究表明，脊髓中还有额外的运动前呼吸神经元。《特殊目的2》将检验这样一种假设，即脊髓中间神经元是神经元回路中的元件，它调节前庭系统对空气进出肺的运动的影响。呼吸肌的规律性收缩也是导致呕吐的另一个原因；前庭信号在与晕动病相关的呕吐期间触发了这种运动活动。然而，引起呕吐的神经回路尚未建立，尽管最近的证据表明，内侧延髓网状结构中的细胞是这一途径的重要组成部分。具体目标3将测试这一假设，即内侧延髓网状结构神经元协调导致呕吐(包括与晕动病相关的呕吐)的呼吸肌的模式放电。总之，这些实验应该确定迷路信号在调节呼吸肌的活动以补偿重力对这些肌肉、呼吸道和肺的影响中所起的特殊作用。此外，在姿势改变和呕吐过程中，介导迷路影响呼吸运动神经元放电的运动前神经元的位置和生理特征也将被确定。

DESCRIPTION (provided by applicant): A variety of experimental approaches have established that the vestibular system contributes to making adjustments in the activity of thoracic and abdominal respiratory pump muscles as well as muscles that regulate the resistance of the upper airway during movement and changes in posture. However, these effects are complex, such that the physiological role of the vestibular system in regulating the movement of air in and out of the lungs is not yet clear. Specific Aim 1 of the current proposal will determine this role by examining the consequences of a bilateral labyrinthectomy on the pressure, volume, and flow rate of air exchanged during inspiration and expiration as body orientation with respect to gravity is altered. Prior experiments have also shown that some of the neurons that relay vestibular signals to respiratory motoneurons are located in the medial medullary reticular formation, but that these cells are insufficient to produce vestibulo-respiratory responses. Our anatomical studies and physiological studies by others have revealed that additional premotor respiratory neurons are located in the spinal cord. Specific Aim 2 will test the hypothesis that spinal interneurons are elements in the neuronal circuit that mediates vestibular system influences on the movement of air in and out of the lungs. Patterned contractions of respiratory muscles are additionally responsible for producing vomiting; vestibular signals trigger this motor activity during emesis associated with motion sickness. However, the neural circuit that elicits vomiting has not yet been established, although recent evidence suggests that cells in the medial medullary reticular formation are important components in this pathway. Specific Aim 3 will test the hypothesis that medial medullary reticular formation neurons coordinate the patterned discharges of respiratory muscles that underlie vomiting, including emesis associated with motion sickness. Together, these experiments should establish the particular role that labyrinthine signals serve in adjusting the activity of respiratory muscles to compensate for the effects of gravity on these muscles, the airways, and the lungs. In addition, the location and physiological characteristics of premotor neurons that mediate labyrinthine influences on respiratory motoneuron firing, both during postural alterations and emesis, will be ascertained.