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

项目总结 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，这一建议将弥合解剖电路图之间的差距 以及他们预测的功能角色。具体地说，它将解决 斑块/矩阵状的“模块化”解剖组织，最近表现为下位 丘脑。该声运动核团可细分为模块区域，以高密度为特征 GAD67和其他神经化学标记物的染色，以及表达Calretinin的模外区域。这些 神经化学分区也与连接性的差异相关；例如，大脑 外侧皮质接受来自躯体感觉和运动结构的输入，如背侧柱核和 躯体感觉和运动皮质，而模块外区域接受来自听觉皮质的听觉输入 和下丘的其他区域。目前尚不清楚这种结构性划分是否 产生用于不同类型的信息处理的分离流，如补丁/矩阵中所示 纹状体中的系统。因此，这一建议的目标是确定侧向的模块化是否 皮层在功能水平上是保守的，因此产生了互补的加工区，具有明显的 在声学-运动行为中的作用。我们将探讨两个主要假设：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)模块化区域作为 躯体感觉驱动的听觉信息门控区域。这些假设将使用 结合双光子钙成像、聚类分析、光遗传学和行为学。模块化的单元格 而外侧皮质的模块外区域将响应于声学或躯体运动刺激而成像， 并将使用聚类分析来确定每个激活的神经元群体 情态形成不同的群体。为了确定躯体感觉受体细胞是否在大脑的模块化区域 外侧皮质门控听觉反应，这一途径将被选择性地操纵，而小鼠则执行两个- 另一种非强制选择的声音本地化任务。光学激活和抑制对大鼠脑内皮细胞的影响 将评估体感输入对声音检测行为的影响。上面概述的实验将 进一步描述外侧皮质的功能组织和行为相关性，这可能具有 对正常听力和病理听力都有重要意义。此外，这些实验可能会揭示 关于模块化体系结构的概括原则，这可以为其他模块化提供见解 纹状体结构，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.