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。对于初级视觉皮层（V1）中的神经元，它们的反应取决于 经典感受野和周围环境之间视觉刺激的变化。这一财产被称为 “环绕调制”有力地影响感觉编码，但其幅度和符号灵活地取决于 中心和周围之间的特征的相似程度，例如方向。具体的V1电路 解释环绕调制取向依赖性的方法在很大程度上是未知的。本项目旨在阐明 通过全活体实验研究了环境抑制方向依赖性突触和电路机制 结合双光子（2 P）靶向全细胞电生理学、单细胞分辨率2 P全息 光遗传学绘制突触连接，2 P钙成像记录群体活动。的假设 该项目的一个重要特点是，环绕声抑制的方向依赖性取决于方向调谐 生长抑素（SST）通过来自周围的共调谐激发的中间神经元介导的侧抑制。作为SST interneurons强烈响应大iso取向，但不是交叉取向的视觉刺激，其中中心 和周围是正交的方向，这表明SST中间神经元对空间背景的调节是 关键在于环绕抑制特征依赖性。为了验证调谐特定连接的核心假设， 在视网膜空间中驱动特征偏好，这个项目的目标将首先检查突触驱动 在SST中间神经元中，这引起了它们对中心和周围的相对取向的选择性， 使用新的组合体内2 p钙成像/2 p全息光遗传学方法来测试是否 定向特异性连接支持V1 SST神经元和锥体细胞的生理调谐， 情境刺激这些实验将不仅提供一个机械的理解方面的视觉 计算，但也展示了概念和技术的进步，可广泛应用于其他关键 神经科学的问题

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.