Role of cell-type specific circuits in visual processing

描述（由申请人提供）：特定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。初级视觉皮层（V1）是大脑中最大和最复杂的结构之一，并且最近的几项技术进步使得能够更详细地探测细胞类型特异性与V1范围内的连接性的关系 单元功能，包括取向选择性、孔径调谐、对比度响应功能、增益控制。然而，技术上的限制仍然存在，这在很大程度上限制了这些研究， 转基因小鼠缺乏更复杂的组织，在更高的视觉物种，如猫和猴子。 我们最近开发了用于访问非转基因物种中的特定细胞类型和特定回路的病毒策略（Liu等人，2013年，Curr Biol）为高度视觉哺乳动物结构-功能关系的前所未有的精细研究打开了大门。对于这项提议，我们将应用这些新策略来实现猫V1中特定细胞类型和回路的光遗传学操纵，包括浅层抑制性神经元（Aim 1），对浅层抑制性神经元的长期侧向输入（Aim 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（Aim 3）。具体的问题，我们将解决包括方向选择性和周围抑制是否以及如何相互作用，并介导的每一个这些电路。这些研究将代表最直接的体内评估抑制性神经元和潜在的层内和层间电路的大型，高度视觉的哺乳动物，推进我们的理解，基本的视觉过程如何产生和依赖于复杂的皮质结构。

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.