Higher-Order Thalamic Input to Primary Sensory Cortex

项目摘要/摘要 丘脑的高级核团构成了丘脑的大部分[5]，最近开始 被认为是早期感觉加工的重要贡献者[1，6，8，9，13，16]，但它们对初级感觉加工的输入 人们对感觉皮质的了解还不够深入。HO核包含不同的神经元亚群 不同的连接性，影响了我们对它们传输的消息以及这些消息如何 对大脑皮层处理的每个阶段都有贡献。在躯体感觉系统中，后内侧核 已知(POM)同时接收皮质和皮质下信息[4，5，14]，但不知道是哪种输入 驱动投射到S1的POM神经元的活动，也不知道这个电路如何影响S1的活动。在类似的Ho中 视觉通路，枕(Pulv)也协调皮质区域之间的通信[1，6]，并接收亚 来自上丘的皮质输入[5]。同样，尽管已知Pulv对处理在 V1[8，9]，目前还不知道是什么区域驱动PULV投射到V1，也不知道这条途径如何影响V1中的靶点。 拟议中的实验旨在通过横断面解剖和 丘脑HO核团的生理途径、标测和突触输出特征 老鼠。这项分析将采用新开发的针对亚人群的病毒策略[25，26]来提供 荧光记者和光遗传探针到有问题的投影基团，结合 体外细胞内记录将阐明投射到原发细胞的HO细胞中哪些区域正在驱动活动 大脑皮层，这些输入如何协调，以及HO投射是否驱动或调制S1和V1的反应。 虽然这两个回路中的每一个都对理解感官中的信息处理感兴趣 系统，这两个系统都是研究系统神经科学的中心平台，这个项目将比较 跨两种感觉模式，提供了一种比较/对比功能的潜在模式的方法 连通性。众所周知，HO丘脑核有几个共同的特征[4，5]，和HO(但不是FO) 精神分裂症患者的细胞核缩小，神经元减少[17-19]。目前提出的调查 HO丘脑对初级感觉皮质的输入的性质和组织都将为深入了解丘脑- 早期感觉加工中的皮质关系，以及阐明可能 精神分裂症和其他疾病状态下出现的缺陷是潜在的。 这些数据也将有助于指导未来对相同电路的活体分析。主要培训目标 这项提议的目的是学习如何使用特定于电路的光遗传学技术以及将 协助设计和执行连接细胞、电路和感觉系统的神经科学实验，以及 帮助我发展成为一名独立的研究人员。

PROJECT SUMMARY / ABSTRACT Higher-order (HO) thalamic nuclei make up most of the thalamus [5], and have recently begun to be appreciated as important contributors to early sensory processing [1,6,8,9,13,16], but their inputs to primary sensory cortex are not well understood. HO nuclei contain heterogeneous neuronal sub-populations with differential connectivity, clouding our understanding of the messages they transmit and how these messages contribute to each stage of cortical processing. In the somatosensory system, the Posterior Medial nucleus (POm) is known to receive both cortical and sub-cortical information [4,5,14], but it is not known which inputs drive activity in POm neurons projecting to S1, nor how this circuit affects S1 activity. In the analogous HO visual pathway, Pulvinar (Pulv) also coordinates communication between cortical areas [1,6], and receives sub- cortical input from the Superior Colliculus [5]. Similarly, despite known contributions of Pulv to processing in V1 [8,9], it is not known what areas drive the Pulv projection to V1 nor how this pathway affects targets in V1. The proposed experiments aim to dissect these circuits by means of an intersectional anatomical and physiological approach, mapping and characterizing synaptic inputs and outputs of the HO thalamic nuclei of mice. This analysis will employ newly developed, sub-population-specific viral strategies [25,26] to deliver fluorescent reporters and optogenetic probes to the projection groups in question, in combination with intracellular recordings in vitro that will clarify what areas are driving activity in HO cells projecting to primary cortex, how these inputs coordinate, and whether HO projections drive or modulate responses in S1 and V1. While each of these two circuits alone is of interest to understanding information processing in sensory systems, and both systems are central platforms for studying systems neuroscience, this project will compare across both sensory modalities, providing a way to compare/contrast the underlying patterns of functional connectivity. HO thalamic nuclei are known to have several features in common [4,5], and HO (but not FO) nuclei are shrunken with fewer neurons in schizophrenic patients [17-19]. The current proposal to probe the nature and organization of HO thalamic input to primary sensory cortex will both provide insight into thalamo- cortical relationships in early sensory processing as well as elucidate circuit-level mechanisms that may underlie deficits seen in schizophrenia and other disease states. Data will also be useful in guiding future in vivo analyses of the same circuits. The major training goal of this proposal is to learn how to use circuit-specific optogenetics techniques along with allied skills that will assist in designing and executing neuroscience experiments that bridge cells, circuits, and sensory systems, and help me develop as an independent researcher.