Multiplicative computation in the vestibulo-ocular reflex (VOR)

描述(由申请人提供)：申请的长期目标是了解前庭系统感觉运动转换的神经机制。在过去的几十年里，对VOR的研究已经证实，对给定的头部运动的VOR反应并不是固定的，而是受到行为语境(即观看距离)的调节。疾病或环境变化导致的背景相关VOR增益调制的缺陷可能会严重损害视力。然而，这一重要的VOR功能背后的神经机制仍有待探索。我们最近的研究表明，前庭和眼睛位置信号在直接的VOR通路中的相互作用是乘性的，而不是像目前假设的那样是相加的。我们的建模分析进一步提出了一种新的神经机制，通过观察距离来实现VOR增益调制。该应用的具体目标是使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交互作用。该提议的一个独特的优点是，我们利用前庭系统的声学激活，并利用点击来唤起VOR对单侧前庭刺激的脉冲反应。这一范例允许我们研究神经基础和潜在的VOR增益调制的信号处理。第一个目标是使用单单位记录技术来定量分析支配内直肌或外直肌的运动神经元中前庭和眼睛位置信号的相互作用。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对三组VOR前运动神经元前庭和眼睛位置信号的相互作用进行定量分析。这些实验将确定这些VOR中间神经元是否是乘法计算的地点。计算模型模拟将研究运动前神经元和运动神经元中乘性相互作用背后的细胞机制。这一应用将为了解人类前庭和动眼神经生理学的基础，提高前庭疾病的诊断和治疗水平提供重要的知识。

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.