Multiplicative computation in the vestibulo-ocular reflex (VOR)

描述（由申请人提供）：本申请的长期目标是了解前庭系统中感觉运动转化的神经机制。在过去的几十年中，对VOR的研究已经确定，对给定头部运动的VOR响应不是固定的，而是在行为背景的调制下（即，观看距离）。由疾病或环境变化引起的背景依赖性VOR增益调制的缺陷会严重损害视力。然而，这一重要VOR功能的神经机制仍有待探索。我们最近的研究表明，前庭和眼睛的位置信号在直接VOR通路的相互作用是乘法，而不是目前假设的加法。我们的建模分析进一步提出了一种新的神经机制，实现VOR增益调制的观看距离。本申请的具体目的是采用单单元记录和计算建模方法来进一步研究直接VOR电路的关键部件中前庭和眼睛位置信号的相互作用。该方案的一个独特优点是，我们利用前庭系统的声学激活，并采用点击来唤起VOR对单侧前庭刺激的脉冲响应。这种模式允许我们检查VOR增益调制的神经基板和信号处理。第一个目的是使用单单位记录技术来定量分析前庭和眼位置信号的相互作用，在确定的运动神经元，支配内侧或外侧直肌。这些实验将确定乘法计算是否在VOR通路的运动神经元池中进行。第二个目的是使用单单位记录技术定量分析前庭和眼位置信号在三组VOR前运动神经元中的相互作用。这些实验将确定这些VOR中间神经元是否是乘法计算的位点。计算模型模拟将研究运动前区和运动神经元中乘法相互作用的细胞机制。这一应用将提供重要的知识，了解基本的前庭和眼神经生理学和改善前庭疾病的诊断和治疗人类。

DESCRIPTION (provided by applicant): The long-term objective of the application is to understand the neural mechanisms of sensorimotor transformation in the vestibular system. Over the past several decades, the investigation of the VOR has established that the VOR response to a given head movement is not fixed, but is under the modulation of behavioral contexts (i.e., viewing distance). Deficits in the context-dependent VOR gain modulation resulting from disease or environmental changes can severely impair vision. The neural mechanisms underlying this important VOR function, however, remain to be explored. Our recent studies demonstrate that the interaction of vestibular and eye position signals in the direct VOR pathways is multiplicative, rather than additive as presently assumed. Our modeling analysis further suggests a novel neural mechanism that implements the VOR gain modulation by viewing distance. The specific aims of the application are to employ single unit recording and computational modeling approaches to further study the interaction of vestibular and eye position signals in the key components of the direct VOR circuits. A unique strength of the proposal is that we take advantage of the acoustic activation of vestibular system and employ click to evoke impulse responses of the VOR to a unilateral vestibular stimulation. This paradigm permits us examine the neural substrate and signal processing underlying VOR gain modulation. The first aim is to use single unit recording techniques to quantitatively analyze the interaction of vestibular and eye position signals in identified motoneurons that innervate the medial or lateral rectus muscles. These experiments will identify whether the multiplicative computation is performed in the motoneuron pools of the VOR pathway. The second aim is to use single unit recording techniques to quantitatively analyze the interaction of vestibular and eye position signals in three groups of VOR premotor neurons. These experiments will identify whether these VOR interneurons are the sites for multiplicative computation. Computational model simulation will examine the cellular mechanisms underlying the multiplicative interaction in both premotor and motoneurons. This application will provide important knowledge for understanding the fundamental vestibular and oculomotor neurophysiology and improving the diagnosis and treatment of vestibular disorders in humans.