Parallel Tectothalamic Pathways

平行的顶盖丘脑通路

基本信息

批准号：
9816337
负责人：
MARTHA E BICKFORD
金额：
$ 38.82万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-02 至 2022-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9816337
关键词：
Address Affect Animals Axon Behavior Behavior assessment Bilateral Birds Brain Brain region Cell Nucleus Cells Disease Dyslexia Electric Stimulation Electrodes Electrons Evaluation Freezing Frequencies Glutamates Goals Head Homologous Gene In Vitro Knowledge Link Mammals Measures Mediating Methods Microscopic Midbrain structure Motion Motion Perception Motor Movement Mus Neurons Output Pathway interactions Pattern Property Pulvinar structure Reaction Retina Retinal Running Schizophrenia Sensory Signal Transduction Slice Specificity Stimulus Synapses System Techniques Testing Thalamic structure Visual Visual Fields Visual Motion Visual Pathways Work autism spectrum disorder base behavioral response brain circuitry cell type design experimental study innovation optical fiber optogenetics photoactivation receptive field response superior colliculus Corpora quadrigemina visual motor visual stimulus

项目摘要

Summary/Abstract The proposed experiments are designed to examine how sensory selectivity is adjusted to initiate appropriate behavior. In mice, two fundamental visually-evoked behaviors, freezing and escape, are initiated respectively by the movement of a small disc that moves slowly across the visual field (sweeping), or a disc that rapidly expands to fill the visual field (looming). However, the synaptic interactions that mediate the selection of these visually-evoked responses are largely unknown. In the superior colliculus (SC), wide field vertical (WFV) cells respond to sweeping or looming stimuli and project to the thalamic pulvinar nucleus (PUL), a brain region involved in the initiation of visually-guided behavior. WFV cells receive input from the retina and V1, intrinsic SC neurons, and the parabigeminal nucleus (PBG). Based on previous studies of the avian nucleus isthmi (considered the PBG homologue), we hypothesize that SC-PBG connections gate the responses of WFV cells to their retinal input, and this stimulus selection network determines the subsequent initiation of appropriate behavioral responses. We propose to examine SC-PBG circuits in detail, and test whether manipulating their activity can shift the responsiveness of WFV cells, alter PUL responses to sweeping and looming stimuli, or impact the initiation of visually-evoked freezing and escape behavior. We will study this system at multiple levels, from the ultrastructure of synapses to behavioral assessments, using an array of innovative strategies to examine circuit function with cell type specificity. The specific goals of the proposed experiments are: to characterize the ultrastructure of synaptic input to WFV cells and synaptic connections that link the SC and PBG (Aim 1a), test how optogenetic activation of the synaptic connections between the SC and PBG affect the responsiveness of WFV and PBG cells (Aim 1b), determine whether PUL receptive field properties differ based on their unique responses to WFV cell input (Aim 2a), test whether PUL responses are altered by manipulating SC-PBG circuits (Aim 2b), and determine if chemogenetic manipulation of SC-PBG pathways affects visually-evoked freezing or escape responses (Aim 3). We believe that this integrated approach can address how sensory selectivity is adjusted to initiate appropriate behavior, while providing the precision of single cell circuit analysis.

摘要/摘要提出的实验旨在检查如何调整感官选择性以启动适当行为。在小鼠中，分别启动了两种基本视觉诱发的行为，冻结和逃脱通过一个小光盘的移动，该光盘在视野（扫地）或迅速的光盘上缓慢移动扩展以填充视野（迫在眉睫）。但是，介导这些选择的突触相互作用视觉诱发的响应在很大程度上是未知的。在上丘（SC）中，宽场垂直（WFV）细胞响应扫描或迫在眉睫的刺激，并向丘脑pulvinar核（PUL）发射出来参与视觉引导行为的启动。 WFV细胞从视网膜和V1接收固有的输入 SC神经元和副神经核（PBG）。基于先前对禽核的研究（考虑到PBG同源物），我们假设SC-PBG连接WFV细胞的响应到他们的视网膜输入，此刺激选择网络决定了随后的适当启动行为反应。我们建议详细检查SC-PBG电路，并测试是否操纵其活动可以改变WFV细胞的响应能力，改变对扫描和迫在眉睫的刺激的脉冲反应，或影响视觉诱发的冻结和逃脱行为的启动。我们将以多个从突触的超微结构到行为评估的水平，使用一系列创新策略检查具有细胞类型特异性的电路函数。拟议实验的具体目标是：表征突触输入到WFV单元格和连接SC和SC的突触连接的超微结构 PBG（AIM 1A），测试SC和PBG之间突触连接的光遗传学激活如何影响 WFV和PBG细胞的响应能力（AIM 1B），确定PUL接受场特性是否有所不同根据它们对WFV单元输入的独特响应（AIM 2A），测试脉冲反应是否通过操纵SC-PBG电路（AIM 2B），并确定SC-PBG途径的化学发生操作是否影响视觉引起的冰冻或逃生反应（AIM 3）。我们相信这种综合方法可以解决如何调整感官选择性以启动适当的行为，同时提供精度单细胞电路分析。