Cell-Type-Specific Mechanisms of Contextual Modulation in the Visual Cortex

项目摘要 自然视觉依赖于分割视觉环境中空间分布的刺激并对其进行编码 根据空间背景。对于初级视觉皮质(V1)中的神经元，它们的反应取决于 视觉刺激在经典感受野和周围区域之间的变化。该属性称为 “环绕调制”强烈地影响感觉编码，但其大小和符号灵活地取决于 特征的相似程度，例如中心和周围之间的方向。特定的V1电路 这解释了环绕调制的取向依赖性在很大程度上是未知的。本项目旨在阐明 在体环环绕抑制的突触和环路机制 结合双光子(2P)靶向全细胞电生理、单细胞分辨率2P全息的方法 光遗传学绘制突触连接图，2P钙成像记录群体活动。假说 这个项目的特点是环绕抑制的方位依赖于定向调谐 生长抑素(SST)通过来自周围的共调激发而由神经元间介导的侧向抑制。作为SST 中间神经元对大的等向而不是交叉定向的视觉刺激有强烈的反应，其中中枢 和周围是垂直定向的，这表明SST中间神经元对空间背景的调节是 环绕抑制的特征依赖关键字。测试特定于调谐的连接性的核心假设 跨越视网膜空间的驱动特征偏好，本项目的目的是首先检查突触驱动 在SST中间神经元中，这导致了它们对中心和周围相对方向的选择性，以及下一步 使用一种新的组合体内2p钙成像/2p全息光遗传学方法来测试 特定方向的连接支持V1 SST神经元和锥体细胞的生理调节 语境刺激。这些实验不仅将提供对视觉方面的机械性理解 计算，但也展示了概念和技术的进步，可以广泛应用于其他关键 神经科学中的问题。

Project Summary Natural vision relies on segmenting spatially distributed stimuli within the visual environment and encoding them according to spatial context. For neurons in the primary visual cortex (V1), their response depends on the variance of visual stimuli between the classical receptive field and the surround. This property known as “surround modulation” powerfully influences sensory coding but its magnitude and sign flexibly depends on the degree of similarity of features, such as orientation, between the center and surround. The specific V1 circuits that explain orientation dependence of surround modulation are largely unknown. This project aims to elucidate the synaptic and circuit mechanisms of orientation dependence of surround suppression through an all-in-vivo approach combining two-photon (2P) targeted whole-cell electrophysiology, single-cell resolution 2P holographic optogenetics to map synaptic connectivity, and 2P calcium imaging to record population activity. The hypothesis of this project is that the orientation dependence of surround suppression depends on orientation-tuned somatostatin (SST) interneuron-mediated lateral inhibition via co-tuned excitation from the surround. As SST interneurons respond strongly to large iso-oriented but not cross-oriented visual stimulation where the center and surround are orthogonally oriented, this suggests that the tuning of SST interneurons to spatial context is key to feature dependence of surround suppression. To test the core hypothesis of tuning-specific connectivity driving feature-preference across retinotopic space, the aims in this project will first examine the synaptic drive in SST interneurons that gives rise to their selectivity for relative orientation of the center and surround, and next use a novel combinatory in vivo 2p calcium imaging/2p holographic optogenetic approach to test whether orientation-specific connectivity supports the physiological tuning of V1 SST neurons and pyramidal cells to contextual stimuli. These experiments will not only provide a mechanistic understanding of aspects of visual computation, but also demonstrate conceptual and technical advances that may be applied broadly to other key questions in neuroscience.