Cerebellar computations for sensing self-motion

用于感知自运动的小脑计算

基本信息

批准号：
9243099
负责人：
Trace Lamar Stay
金额：
$ 4.4万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9243099
关键词：
Acceleration Address Adult Affect Animals Behavior Behavioral Brain Cell Communication Cells Cerebellar cortex structure Cerebellar vermis structure Cerebellum Code Computer Simulation Cre-LoxP Data Development Equilibrium Esthesia Fiber Force of Gravity Foundations Gated Ion Channel Genetic Goals Gravitation Hair Cells Head Health Human Individual Ion Channel Gating Laws Learning Linear Models Link Lobule Macaca Maintenance Mechanics Mediating Methods Modeling Monkeys Motion Motor Mus Neuraxis Neurons Output Perception Phase Play Positioning Attribute Posture Process Property Purkinje Cells Research Role Self-control as a personality trait Semicircular canal structure Sensory Sensory Process Signal Transduction Synapses System Testing Time Translations Walking Work analytical tool awake base experience experimental study extracellular genetic approach in vivo mouse model neuromechanism neurotransmission operation otoconia physical model public health relevance relating to nervous system response sensory input theories tool vesicular GABA transporter

项目摘要

DESCRIPTION (provided by applicant): There is mounting evidence that the cerebellum might play a major role in sensory function, even though it is better known for controlling motor behavior. To support this hypothesis, one prediction is that the cerebellum exerts a powerful influence over how sensory signals are processed. This prediction raises a critical question - what neural mechanisms in the cerebellum control ongoing sensory computations? To address this problem I postulated that Purkinje cells receive and encode key signals that are necessary for normal sensation. Based on multiple computations making up a well-defined sensory process, I further postulated that Purkinje cells could influence vestibular perception in both development and adulthood. But in order to fully test this I had to devise a mouse model that would enable me to induce tractable changes in sensory behavior after manipulating the flow of information in the cerebellum. For this, we developed a conditional genetic strategy to manipulate synaptic neurotransmission in particular circuits. Our approach uses the Cre/loxP genetic approach to selectively block the expression of the vesicular GABA transporter VGAT in Purkinje cells. By doing so, I can now delineate the mechanisms for how the Purkinje cells control motion selectivity. I have compelling preliminary data from my mice showing that altering cerebellar activity obstructs vestibular sensory computations in vivo. I propose to expand on this work by testing the hypothesis that Purkinje cell communication to target neurons controls self-motion sensation by dissociating sensory flow into circuits for tilt and translation. In Aim 1, I wll determine Purkinje cell output is required for initial establishment of internal representations of inertial versus gravitational acceleration during development. In Aim 2, I will determine whether GABAergic signals from Purkinje cells are necessary for dissociating tilt and translation during ongoing adult behavior. The completion of my aims will define the mechanistic actions of how the cerebellum impacts vestibular sensation and provide a more complete wiring diagram for how sensory signals are transformed into behavioral outputs.

描述（由申请人提供）：越来越多的证据表明小脑可能在感觉功能中发挥重要作用，尽管小脑以控制运动行为而闻名。为了支持这一假设，一个预测是小脑对感觉功能发挥着强大的影响。这个预测提出了一个关键问题：小脑中的哪些神经机制控制着正在进行的感觉计算？为了解决这个问题，我假设浦肯野细胞接收并编码正常所需的关键信号。基于构成明确感觉过程的多次计算，我进一步假设浦肯野细胞可以影响发育和成年期的前庭知觉，但为了充分测试这一点，我必须设计一个小鼠模型，使我能够做到这一点。为此，我们开发了一种条件遗传策略来操纵特定回路中的突触神经传递。选择性阻断浦肯野细胞中囊泡 GABA 转运蛋白 VGAT 的表达通过这样做，我现在可以描述浦肯野细胞如何控制运动选择性的机制，我从小鼠身上获得了令人信服的初步数据，表明改变小脑活动会阻碍前庭感觉计算。我建议通过测试以下假设来扩展这项工作：浦肯野细胞与目标神经元的通信通过将感觉流分离到倾斜和平移电路来控制自我运动感觉。在目标 1 中，我将确定浦肯野细胞输出是初始建立内部表示所需的在目标 2 中，我将确定来自浦肯野细胞的 GABA 信号对于成人持续行为过程中的分离倾斜和平移是否是必需的。提供更完整的接线图，说明如何将感官信号转化为行为输出。