Large-scale recording of visually-evoked activity in the mouse superior colliculus: functionality, topology, network properties and coding

项目摘要 在这里，我们建议开发和集成一套实验和计算工具，以 测量小鼠大量神经元的视觉反应和网络特性 上丘(SC)，以确定这些特性在运动过程中如何变化，以及 皮质和特定的视网膜输入对这些特性的贡献。小鼠的SC是皮质下的 视觉、触觉和听觉相结合的区域，以启动眼睛的定向运动 和Head，是研究特定电路在发育过程中如何形成的一个有吸引力的模型。我们的 用于记录神经活动的高密度、高通道计数硅探针的开发有几个 与其他方法相比的显著优点：(1)记录神经元空间的效率高 和时间视觉反应特性；(2)快速学习拓扑/功能的能力 在一个单一的动物中，以统一的方式在大视野内的大神经元群体中组织； (3)研究神经元和网络之间的相关活动和连通性的可能性 节奏；(4)确定与行为状态相关的视觉反应差异的能力 比如运动。 目标1中提出的实验将测量视觉上的功能和拓扑性质- 清醒和头部固定在自由漂浮的聚苯乙烯泡沫塑料球上的小鼠SC中的反应神经元 用作球形跑步机。对于每个神经元，空间感受野(RF)，时间滤波 尖峰触发平均(STA)、方向和取向选择性以及空间的非线性 求和将被确定，并与其在SC中的位置相关，并与运动相关。 目标2将应用目标1中开发的记录和数据分析工具来理解 缺乏对SC的皮质输入或缺乏开关方向的突变小鼠的电路变化 选择视网膜神经节细胞(DS RGCs)。这将使我们能够确定大脑皮层的贡献 和DS RGCs对SC神经元的感受野特性的影响。 完成后，对SC神经元及其拓扑组织进行全面分类，并 它们的编码特性将掌握在手中。然后，我们将利用不断扩展的 改变视觉功能的遗传工具(包括光遗传学)，以及复杂的小鼠模型 改变活动模式的神经系统疾病，如自闭症和精神分裂症。这些是相同的 这些技术将有助于理解具有更复杂视觉的动物大脑区域的电路 系统和大脑回路，如猫、雪貂和非人类灵长类动物。

Project Summary Here we propose to develop and integrate a suite of experimental and computational tools to measure the visual response and network properties of a large population of neurons in the mouse superior colliculus (SC), to determine how these properties change during locomotion, and the contribution of cortical and specific retinal inputs to these properties. The mouse SC is a subcortical area that integrates vision with touch and hearing to initiate orienting movements of the eyes and head, and is an attractive model to study how specific circuits form during development. Our development of high-density, high-channel count silicon probes to record neural activity has several significant advantages compared to alternative methods: (1) high efficiency for recording neuron spatial and temporal visual response properties; (2) the ability to rapidly study the topological/functional organization in a large neuron population over a wide field of view in a uniform way in a single animal; (3) the possibility to study correlated activity and connectivity among neurons as well as network rhythms; (4) the ability to ascertain differences in visual responses associated with behavioral state such as locomotion. Experiments proposed in Aim 1 will measure the functional and topological properties of visually- responsive neurons in the SC of mice that are awake and head-fixed on a freely-floating Styrofoam ball used as a spherical treadmill. For each neuron, the spatial receptive field (RF), the temporal filtering spike-triggered average (STA), direction and orientation selectivity, and the non-linearity of spatial summation will be determined and correlated with its location in the SC and correlated with locomotion. Aim 2 will apply the recording and data analysis tools developed in Aim 1 toward understanding the changes in circuitry in mutant mice that lack cortical inputs to the SC or lack On-Off direction selecive retinal ganglion cells (DS RGCs). This will allow us to determine the contribution of the cortex and DS RGCs toward the receptive field properties of SC neurons. Upon completion, a comprehensive classification of SC neurons, their topological organization, and their coding properties will be in hand. We will then take advantage of the ever-expanding availability of genetic tools (including optogenetics) that alter visual function, and mouse models of complex neurological disease that have altered activity patterns such as autism and schizophrenia. These same techniques will be useful to understand the circuitry of brain areas of animals with more complex visual systems and brain circuitry such as cat, ferret, and non-human primates.