Multiplicative computation in the vestibulo-ocular reflex (VOR)

描述（由申请人提供）：该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。在过去的几十年里，对 VOR 的研究表明，VOR 对给定头部运动的响应不是固定的，而是受到行为环境（即观看距离）的调节。疾病或环境变化导致的上下文相关 VOR 增益调制缺陷会严重损害视力。然而，这一重要 VOR 功能背后的神经机制仍有待探索。我们最近的研究表明，直接 VOR 通路中前庭和眼位信号的相互作用是乘性的，而不是目前假设的加性。我们的建模分析进一步提出了一种新颖的神经机制，通过观察距离实现 VOR 增益调制。该应用的具体目标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位信号的相互作用。该提案的独特优势在于，我们利用前庭系统的声学激活，并利用点击来诱发 VOR 对单侧前庭刺激的脉冲响应。这个范式允许我们检查 VOR 增益调制背后的神经基质和信号处理。第一个目标是使用单单元记录技术来定量分析所识别的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。第二个目标是使用单单元记录技术定量分析三组 VOR 前运动神经元中前庭和眼睛位置信号的相互作用。这些实验将确定这些 VOR 中间神经元是否是乘法计算的场所。计算模型模拟将检查运动前神经元和运动神经元乘法相互作用背后的细胞机制。该应用将为理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.