Functional implications of a patch/matrix-like compartmental organization in the mouse inferior colliculus

项目摘要 系统神经科学中一个尚未解决的主要问题是专门的解剖结构是否支持 行为中的特定功能。因此，本提案将弥合解剖电路图之间的差距 以及它们的预测功能。具体而言，它将解决的功能后果， 补片/矩阵样“模块化”解剖组织，最近在下 丘这种声运动核可以细分为模块化区域，其特点是高密度 GAD 67和其他神经化学标记物以及表达钙视网膜蛋白的模块外区域的染色。这些 神经化学分区也与连接性的差异相关;例如， 外侧皮质接收来自躯体感觉和运动结构的输入，例如背柱核， 躯体感觉和运动皮层，而模块外区域接收来自听觉皮层的听觉输入 以及下丘的其他区域。目前尚不清楚这种结构划分是否 对于不同类型的信息处理，产生了分离的流，如在补丁/矩阵中所见 纹状体系统。因此，本提案的目标是确定横向 皮质在功能水平上是保守的，因此产生了具有不同功能的互补处理区。 在听觉运动行为中的作用两个主要的假设将探讨：1），听觉和躯体运动， 信号激活外侧皮质中不同的细胞群，以及2）模块化区域充当 躯体感觉驱动的听觉信息门控区域。这些假设将使用 双光子钙成像、聚类分析、光遗传学和行为的组合。单元格模块化 并且外侧皮质的模块外区域将响应于声音或躯体运动刺激而成像， 和聚类分析将用于确定是否由每个激活的神经元群体 形态形成不同的组。为了确定是否在模块化区域的体感受体细胞， 外侧皮层门控听觉反应，这条通路将被选择性地操纵，而小鼠执行两个- 替代非强制选择声音定位任务。光激活和抑制的影响， 将评估对声音检测行为的体感输入。上述实验将 进一步表征外侧皮质的功能组织和行为相关性，这可能具有 对正常和病理性听力都有重要意义。此外，这些实验可能揭示 关于模块化架构的可推广原则，可以为其他模块化架构提供见解。 结构，如纹状体。

PROJECT SUMMARY A major unresolved question in systems neuroscience is whether specialized anatomical structures support specific functions in behavior. Therefore, this proposal will bridge the gap between anatomical circuit diagrams and their predicted functional roles. Specifically, it will address the functional consequences of the patch/matrix-like “modular” anatomical organization that has recently been characterized in the inferior colliculus. This acoustico-motor nucleus can be subdivided into modular regions, characterized by high density staining for GAD67 and other neurochemical markers, and extramodular regions that express calretinin. These neurochemical divisions also correlate with differences in connectivity; for example, modular regions of the lateral cortex receive input from somatosensory and motor structures, such as the dorsal column nuclei and somatosensory and motor cortices, while extramodular areas receive auditory inputs from the auditory cortex and other regions of the inferior colliculus. It is presently unknown whether this structural compartmentalization gives rise to segregated streams for distinct types of information processing, as is seen in the patch/matrix system in the striatum. Therefore, the goal of this proposal is to determine whether the modularity of the lateral cortex is conserved at the functional level, thus giving rise to complementary processing zones with distinct roles in acoustico-motor behavior. Two main hypotheses will be explored: 1) that auditory and somato-motor signals activate distinct populations of cells in the lateral cortex, and 2) that modular zones serve as somatosensory-driven gating regions for auditory information. These hypotheses will be tested using a combination of two-photon calcium imaging, clustering analysis, optogenetics, and behavior. Cells in modular and extramodular regions of the lateral cortex will be imaged in response to acoustic or somato-motor stimuli, and clustering analysis will be used to determine whether the populations of neurons activated by each modality form distinct groups. To determine whether somatosensory-recipient cells in modular regions of the lateral cortex gate auditory responses, this pathway will be selectively manipulated while mice perform a two- alternative unforced-choice sound localization task. The effect of optical activation and inhibition of the somatosensory inputs on sound detection behavior will be assessed. The experiments outlined above will further characterize the functional organization and behavioral relevance of the lateral cortex, which could have important implications for both normal and pathological hearing. Furthermore, these experiments may reveal generalizable principles regarding modular architectures, which could provide insights into other modular structures, such as the striatum.