Neural Circuits and Function in Primary Visual Cortex

描述（由申请人提供）：视觉知觉是由视网膜、视觉皮层和皮层下脑结构中的神经元之间复杂的相互作用介导的。视觉对人类和其他灵长类动物的重要性反映在大脑皮层用于处理视觉信息的巨大比例上。因此，视觉处理的缺陷尤其使人衰弱，而且不仅是由眼睛的异常引起的，而且是由皮层回路的异常引起的。例如，儿童时期的斜视或弱视会对处理视觉信息的皮层回路产生长期影响。也有证据表明，某些形式的阅读障碍是由中枢视觉系统异常引起的。本研究旨在了解初级视觉皮层（V1）的神经回路的组织和功能，更广泛的目标是了解神经回路如何介导视觉感知。具体来说，这些研究旨在确定：1)投射到特定的胃外视觉皮层区域和皮层下结构的V1细胞类型的详细形态学特性；2) V1神经元直接局部输入的来源，并投射到特定的皮层外视觉区和皮层下结构；3)视网膜神经节细胞类型通过LGN向V1的功能和解剖上不同的隔室提供输入；4)个体神经元的体内视觉反应特性如何与这些相同细胞类型的连通性相关，这是我们之前和正在进行的体外研究揭示的。前3个目标将使用在首席研究员实验室开发的新型病毒电路追踪工具来实现。这些工具允许完全填充已识别的投射神经元和来自特定投射神经元的单突触限制性跨突触标记。最后一个目标是通过记录V1神经元的视觉反应并用染料标记它们来将解剖学上不同的细胞类型与功能联系起来。提出的研究将使视觉皮层回路有一个前所未有的视角——它们将揭示视觉皮层神经元的详细连接，以及这些回路如何与组成神经元的功能特性相关联。总结：视觉处理的缺陷尤其使人衰弱，它不仅是由眼睛的异常引起的，而且是由皮层回路的异常引起的。这些研究将揭示视觉皮层回路的正常组织和功能，这对于理解视觉功能障碍的潜在原因是必要的。

DESCRIPTION (provided by applicant): Visual perception is mediated by complex interactions amongst neurons in the retina, visual cortex, and subcortical brain structures. The importance of vision to humans and other primates is reflected in the enormous percentage of cerebral cortex devoted to processing visual information. Thus, deficits in visual processing are particularly debilitating and arise from abnormalities not only in the eye, but also in cortical circuitry. For example, strabismus or amblyopia during childhood can have long-lasting effects on the cortical circuits that process visual information. There is also evidence that some forms of dyslexia result from central visual system abnormalities. The proposed studies are aimed at understanding the organization and function of neural circuits to, from, and within the primary visual cortex (V1), with the broader objective of understanding how neural circuits mediate visual perception. In particular, these studies aim to identify: 1) the detailed morphological properties of V1 cell types that project to particular extrastriate visual cortical areas and subcortical structures; 2) the sources of direct local input to V1 neurons with projections to particular extrastriate visual cortical areas and subcortical structures; 3) the retinal ganglion cell types that provide input, via the LGN, to functionally and anatomically distinct compartments in V1; and 4) how the in vivo visual response properties of individual, identified neurons correlate with the connectivity of these same cell types, as revealed by our previous and ongoing in vitro studies. The first 3 goals will be achieved using novel viral circuit tracing tools developed in the principal investigator's laboratory. These tools allow complete filling of identified projection neurons and monosynaptically-restricted transynaptic labeling from specific projection neurons. The last aim is accomplished by recording visual responses of V1 neurons and labeling them with dye to correlate anatomically distinct cell types with function. The proposed studies will allow an unprecedented view of visual cortical circuits - they will reveal the detailed connectivity of neurons in visual cortex and how these circuits relate to the functional properties of the component neurons. Lay summary: Deficits in visual processing are particularly debilitating and arise from abnormalities not only in the eye, but also in cortical circuitry. The proposed studies will reveal the normal organization and function of visual cortical circuits, which is necessary to understand the underlying causes of visual dysfunction.