Parallel Tectothalamic Pathways

总结/摘要 拟议的实验旨在研究如何调整感官选择性，以启动适当的 行为在小鼠中，两种基本的视觉诱发行为，冻结和逃避，分别启动 通过一个小圆盘的运动，缓慢地穿过视野（扫描），或者一个圆盘迅速地 展开以填充视野（若隐若现）。然而，介导这些选择的突触相互作用 视觉诱发的反应在很大程度上是未知的。在上级丘（SC），宽视野垂直（WFV）细胞 对扫描或隐约可见的刺激作出反应，并投射到丘脑枕核（PUL），这是一个大脑区域 参与视觉引导行为的启动。WFV细胞接收来自视网膜和V1的输入， SC神经元和二叠旁核（PBG）。根据以往对鸟类峡核的研究， （考虑PBG同源物），我们假设SC-PBG连接门控WFV细胞的反应 他们的视网膜输入，这个刺激选择网络决定了随后启动适当的 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细胞的反应性，改变PUL对扫描和隐约可见的刺激的反应，或 影响视觉诱发的冻结和逃避行为的启动。我们将研究这个系统在多个 水平，从突触的超微结构到行为评估，使用一系列创新策略 用细胞类型特异性检查电路功能。拟议实验的具体目标是： 表征到WFV细胞的突触输入和连接SC和 PBG（目标1a），测试SC和PBG之间突触连接的光遗传学激活如何影响SC和PBG之间的突触连接。 WFV和PBG细胞的反应性（目的1b），确定PUL感受野特性是否不同 根据其对WFV电池输入的独特响应（目标2a），测试PUL响应是否因 操纵SC-PBG回路（目的2b），并确定SC-PBG通路的化学遗传操纵 影响视觉诱发的冻结或逃避反应（目标3）。我们认为，这种综合办法可以 解决如何调整感官选择性以启动适当的行为，同时提供精确的 单细胞电路分析

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.