Physiology of Vestibular Compensation

描述(申请人提供)：来自一个迷宫的前庭信号中断导致由高频、高加速度头部运动引起的角状前庭眼反射(VOR)的不对称。在上一个资助期的研究已经阐明了松鼠猴角度VOR的线性和非线性成分，展示了这些成分对放大或最小化眼镜的选择性适应，比较了松鼠猴子和猕猴水平角度VOR对快速旋转的反应，确定了前庭神经传入对快速头部旋转的反应特性，并分析了庆大霉素单侧耳毒性前庭损伤后角度VOR、传入细胞和毛细胞的变化。 拟议的研究建立在以前通过研究取得的成就的基础上，这些研究被组织成三个具体目标。这些实验在龙猫和猕猴身上进行。Aim I的研究将确定前庭神经传入对加速步骤的反应，并研究不规则放电传入对这些快速头部旋转所诱发的水平VOR的贡献。传递到每个迷路的双侧阳极电流将被用来在快速头部旋转过程中显著减弱或抑制不规则传入。在猕猴身上进行的实验将包括分析正常的VOR以及随后的眼镜诱导的适应。目的研究单侧前庭病变侧传入神经和对侧(完整)迷路传入神经在VOR代偿中的作用。保留静息率但取消或显著减弱运动反应的单侧病变涉及鼓室内注射庆大霉素。目的III研究单侧迷路切除后猕猴水平VOR代偿性改变的神经相关性。这些实验将确定单侧迷路切除后对侧前庭神经传入的放电特性是否发生变化。在单侧迷路切除后，将研究前庭核神经元介导VOR的动力学。本体感觉输入和预期机制在改变这些中枢神经元反应中的作用将通过比较主动和被动产生的头部-身体和全身旋转过程中的神经元反应来确定。

DESCRIPTION (provided by applicant): Disruption of vestibular signals from one labyrinth results in asymmetries in the angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration head movements. Studies during the previous funding period have elucidated linear and nonlinear components of the angular VOR in the squirrel monkey, demonstrated selective adaptation of these components with magnifying or minimizing spectacles, compared the horizontal angular VOR in squirrel monkeys and macaques in response to rapid rotations, defined the response properties of vestibular-nerve afferents to rapid head rotations, and analyzed changes in the angular VOR, afferents, and hair cells following unilateral ototoxic vestibular injury with gentamicin. The proposed research builds upon previous accomplishments through studies that are organized into three specific aims. The experiments are performed in chinchillas and in macaques. Studies in Aim I will define the responses of vestibular-nerve afferents to steps of acceleration and study the contributions of irregularly discharging afferents to the horizontal VOR evoked by these rapid head rotations. Bilateral, anodal galvanic currents delivered to each labyrinth will be used to substantially attenuate or silence irregular afferents during rapid head rotations. The experiments that are conducted in macaques will involve analysis of the normal VOR as well as following spectacle-induced adaptation. Aim II will investigate the contribution to VOR compensation of preserved resting rate in afferents on the side of a unilateral vestibular lesion and of afferents from the contralesional (intact) labyrinth. The unilateral lesion that preserves resting rate but abolishes or markedly attenuates responses to motion involves intratympanic injection of gentamicin. Aim III will examine neural correlates of compensatory changes in the horizontal VOR in macaques after unilateral labyrinthectomy. These experiments will determine if the discharge properties of vestibular-nerve afferents on the contralateral side change following unilateral labyrinthectomy. The dynamics of vestibular nuclei neurons that mediate the VOR will be studied following unilateral labyrinthectomy. The role of proprioceptive inputs and anticipatory mechanisms in modifying the responses of these central neurons will be determined by comparing neuronal responses during actively and passively generated head-on-body and whole-body rotations.