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化的神经机制。在过去的几十年里，对VOR的研究已经确定，VOR对给定头部运动的反应不是固定的，而是受到行为环境（即观看距离）的调节。由于疾病或环境变化导致的上下文依赖的VOR增益调制缺陷可严重损害视力。然而，这种重要的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VOR通路中的相互作用是乘法的，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，通过观看距离实现VOR增益调制。该应用程序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电路关键组件中前庭和眼睛位置信号的相互作用。该建议的独特之处在于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。这个范例允许我们检查VOR增益调制的神经基底和信号处理。第一个目标是使用单单元记录技术定量分析前庭和眼睛位置信号在确定的运动神经元中的相互作用，这些运动神经元支配内侧或外侧直肌。这些实验将确定是否在VOR通路的运动神经元池中进行乘法计算。第二个目的是利用单单元记录技术定量分析三组VOR前运动神经元前庭和眼位置信号的相互作用。这些实验将确定这些VOR中间神经元是否是进行乘法计算的位点。计算模型模拟将检查在前运动和运动神经元乘法相互作用的细胞机制。这一应用将为了解基本的前庭和动眼神经生理学以及改善人类前庭疾病的诊断和治疗提供重要的知识。

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.