Spatiotemporal control of dendritic inhibition by a family of diverse somatostatin-expressing interneurons

摘要 GABA能中间神经元(INS)是一组不同的神经元，在中枢神经系统的信号处理中起重要作用。 大脑皮层。此外，这些神经元的功能障碍与许多疾病有关，包括 从癫痫到精神分裂症、焦虑症和自闭症。该项目的重点是GABA能惯导系统 表达神经肽生长抑素(SST)的细胞。这些细胞是人类第二大胰岛素家族 大脑皮层。SST INS在锥体细胞(PC)和其他中间神经元的树突上形成突触 已被证明对树枝整合以及非线性树枝操作很重要，钙 信号和可塑性。SST INS是最近提出的，基于对其体内模式的分析 在多种类型的感觉皮质中的活动，参与被认为是去抑制的典型回路 在大脑状态依赖的皮质功能控制中起重要作用。然而，这些研究仅限于 皮质层较浅。利用一种新的方法进行基因标记的活体记录和标记 我们首次从整个皮质柱的SST记录到整个大脑的神经元 并在躯体感觉皮质的L5/6发现了一种未知的SST INS多样性。SST in亚型 轴突的层状分布不同，在体内的活动模式也不同。利用 我们对SST多样性的扩展理解以及新的遗传工具的可用性 SST在亚型中的识别和操纵具有更高的特异性，本项目的目标是测试 不同亚型SST对特定PC树突状分支活性的差异控制假说 行为。我们将研究L5/6 SST IN亚型与不同类型的L5 PC的连接性，并确定 L5-PC树突上IN突触的亚细胞定位(AIM 1)。在Aim 2中电生理学 将使用记录、钙成像和光遗传操作来研究不同的SST的功能 锥体细胞主动触摸反应的亚型及其声音的跨模式调制。目标3 我将开发一个基于实验的PC树突中信息选择性门控模型，该模型由 SST in亚型。这些研究将促进我们对SST的功能和TOP机制的理解 感觉加工的下调。

Summary GABAergic interneurons (INs) are a diverse group of neurons with critical roles in signal processing in the cerebral cortex. Moreover, malfunction of these neurons has been implicated in a number of diseases ranging from epilepsy to schizophrenia, anxiety disorders and autism. This project is focused on the GABAergic INs that express the neuropeptide somatostatin (SST). These cells represent the second largest family of INs in the neocortex. SST INs make synapses on the dendrites of pyramidal cells (PCs) and other interneurons and have been shown to be important for dendritic integration, as well as non-linear dendritic operations, Ca2+ signaling, and plasticity. SST INs were recently suggested, based on the analysis of their patterns of in vivo activity in multiple types of sensory cortices, to be involved in a disinhibitory canonical circuit that is thought to be important in brain state-dependent control of cortical function. However, these studies have been limited to superficial cortical layers. Using a new method for the in vivo recording and labeling of genetically-tagged neurons throughout the brain we recorded for the first time from SST IN throughout the whole cortical column and discovered an unappreciated diversity of SST INs in L5/6 of somatosensory cortex. SST IN subtypes differed in the laminar distribution of their axon and had distinct patterns of in vivo activity. Taking advantage of our expanded understanding of SST IN diversity and the availability of novel genetic tools that allow the identification and manipulation of SST IN subtypes with increased specificity, the goal of this project is to test the hypothesis that SST IN subtypes differentially control the activity of specific PC dendritic branches during behavior. We will study the connectivity of L5/6 SST IN subtypes to different types of L5 PCs and determine the subcellular localization of IN synapses on the L5 PC dendrite (Aim 1). In Aim 2 electrophysiological recording, Ca2+ imaging and optogenetic manipulations will be used to investigate the function of distinct SST In subtypes on active touch responses in pyramidal cells and their cross-modal modulation by sound. Aim 3 will develop an experimentally-based model of the selective gating of information in PC dendrites mediated by SST IN subtypes. These studies will advance our understanding of SST IN function and the mechanisms of top down modulation of sensory processing.