Role of cell-type specific circuits in visual processing

描述(由申请人提供)：特定的细胞类型及其连接性是神经功能和选择性的关键决定因素。初级视觉皮质(V1)是大脑中最大和最复杂的结构之一，最近的几项技术进步使更详细地探测到一系列V1的细胞类型特定关系与连接性 单元功能，包括取向选择性、光圈调谐、对比度响应功能、增益控制。然而，技术限制仍然存在，这在很大程度上将这些研究限制在 转基因小鼠缺乏更复杂的组织，在猫和猴子等视觉较高的物种中发现。我们最近开发了用于访问非转基因物种中特定细胞类型和特定回路的病毒策略(Liu等人，2013，Curr Biol)，为高度视觉哺乳动物的结构-功能关系的前所未有的精细研究打开了大门。在这项提议中，我们将应用这些新策略来实现对CAT V1中特定细胞类型和电路的光遗传操作，包括浅层抑制神经元(目标1)、向浅层抑制神经元的长程侧向输入(目标2)以及直接(或间接)与浅层神经元相互作用的第5层和第6层皮质下投射神经元(目标3)。我们将解决的具体问题包括定向选择性和环绕抑制是否以及如何相互作用，并由这些回路中的每一个来调节。这些研究将代表对大型高度视觉哺乳动物的抑制性神经元和潜在的层内和层间电路的最直接的在体评估，促进我们对基本视觉过程如何产生和依赖于复杂的皮质结构的理解。

DESCRIPTION (provided by applicant): Specific cell types and their connectivity are a key determinant in neural function and selectivity. Primary visual cortex (V1) is one of the largest and most complex structures in the brain and several recent technological advances have enabled more detailed probing of cell type specific relationships to connectivity for a range of V1 cell functions, including orientation selectivity, aperture tuning, contrast response functions, an gain control. Nevertheless, technical limitations remain that have largely limited these studies to transgenic mice which lack more complex organization found in higher visual species like cat and monkey. We recently developed viral strategies for accessing specific cell types and specific circuits in non-transgenic species (Liu et al., 2013, Curr Biol) opening the door for unprecedented fine scale study of structure-function relationships in highly visual mammals. For this proposal we will apply these new strategies to enable optogenetic manipulation of specific cell types and circuits in cat V1, including superficial layer inhibitory neurons (Aim 1), long-ran lateral inputs to superficial inhibitory neurons (Aim 2), and layer 5 and 6 subcortical projection neurons that directly (or indirectly) interact with superficial layer neurons (Aim 3). Specific questions that we will address include whether and how orientation selectivity and surround suppression interact and are mediated by each of these circuits. These studies will represent the most direct in vivo assessment of inhibitory neurons and underlying intra- and inter-laminar circuitry of a large, highly visual mammal, advancing our understanding of how basic visual processes arise and depend on complex cortical structure.