Signal transformations in the vestibulo-ocular circuit

前庭眼回路中的信号转换

基本信息

批准号：
10307123
负责人：
Trace Lamar Stay
金额：
$ 6.76万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10307123
关键词：
Address Affect Afferent Pathways Area Awareness Behavioral Biological Assay Biomedical Engineering Brain Stem Cerebellar Cortex Cerebellum Chemosensitization Collaborations Computer Models Data Disease Electrodes Electrophysiology (science)Environment Equilibrium Equipment Eye Eye Movements Fiber Genetic Goals Head Head Movements Health Human Individual Lead Learning Long-Term Potentiation Medial Mental Depression Modality Modification Molecular Motor Motor output Mus Musculoskeletal Equilibrium Nature Neurons Neurosciences Noise Nuclear Organ Outcome Study Output Pathway interactions Pattern Phase Play Population Positioning Attribute Posture Process Purkinje Cells Reflex action Reflex control Reflex eye movement Research Role Rotation Self Perception Sensory Signal Transduction Silicon Site Stimulus Structure of purkinje fibers Synapses System Techniques Testing Therapeutic Effect Tissues Training Universities Variant Visual base behavior test cell type design experimental study eye velocity granule cell in vivo innovation motor behavior motor control neurotransmission novel oculomotor postsynaptic presynaptic relating to nervous system response sample fixation sensory input signal processing vestibulo-ocular reflex visual stimulus visual tracking

项目摘要

PROJECT SUMMARY The vestibular system is essential for many functions, including maintaining balance and orchestrating reflexes. For instance, the vestibulo-ocular reflex (VOR) is necessary for stabilizing eye fixation with head movement. However, the role that individual cell types play in orchestrating the VOR motor response is not fully determined. Previous research has been limited by serial single-unit recordings, which cannot capture the dynamics of simultaneous activity across synapses, and limited behavioral testing sets, which result in confounding co- variation between predictor variables. Three related questions of VOR function are how vestibular information is integrated with other input pathways (e.g. visual and efference copy inputs), how neural processing changes over the course of VOR adaptation (specifically, to gain or phase), and what mechanistic means are used to create VOR learning. The goal of this proposal is to answer these three questions in mice, using large-scale in vivo electrophysiology during innovative probe conditions, carefully designed training sets that dissociate learned timing from learned gain responses, and precise genetic interrogation to conditionally manipulate molecular signaling at a key point in the VOR circuit. Neural responses will be analyzed with unbiased computational models, to fully establish signal transformations between circuit nodes. Determining the signal content in the cerebellum and brainstem vestibulo-ocular neurons will help answer a decades-long debate about the nature of plasticity during in vivo learning (depression vs potentiation). Resolving the differences in filtering that occur over adaptation will illuminate learning motifs of the circuit. Assessing the relative contribution of presynaptic plasticity to VOR learning will better define specific molecular pathways that could be targeted for specific therapeutic effects. These experiments will be performed in an ideal research setting at Stanford University, with specially-prepared equipment and access to leading experts in vestibular research and neuroscience more generally. The overall outcomes of this study will contribute significantly to the goal of defining normal and disordered processes in vestibular function.

项目概要前庭系统对于许多功能至关重要，包括维持平衡和协调反射。例如，前庭眼反射（VOR）对于头部运动时稳定眼睛注视是必要的。然而，单个细胞类型在协调 VOR 运动反应中所起的作用尚未完全确定。先前的研究受到连续单个单元记录的限制，无法捕捉到的动态跨突触的同时活动和有限的行为测试集，这会导致混淆预测变量之间的变化。 VOR 功能的三个相关问题是前庭信息如何与其他输入途径（例如视觉和输出复制输入）集成，神经处理如何变化在 VOR 适应过程中（特别是增益或相位），以及使用什么机械手段创建 VOR 学习。该提案的目标是通过大规模的实验来回答小鼠的这三个问题。创新探针条件下的体内电生理学，精心设计的训练集可分离所学知识根据习得的增益反应进行计时，并通过精确的基因询问来有条件地操纵分子 VOR 电路中关键点的信令。神经反应将通过无偏见的计算进行分析模型，以完全建立电路节点之间的信号转换。确定信号内容小脑和脑干前庭眼神经元将有助于回答长达数十年的关于前庭眼神经元本质的争论体内学习期间的可塑性（抑制与增强）。解决过滤中出现的差异过度适应将阐明电路的学习主题。评估突触前的相对贡献 VOR 学习的可塑性将更好地定义可以针对特定目标的特定分子途径治疗效果。这些实验将在斯坦福大学理想的研究环境中进行，专门准备的设备以及接触前庭研究和神经科学领域领先专家的机会更多一般来说。这项研究的总体结果将对定义正常和不正常的目标做出重大贡献前庭功能过程紊乱。