Neural Circuits and Function in Primary Visual Cortex

描述(申请人提供)：视觉感知是由视网膜、视觉皮质和皮质下大脑结构中神经元之间的复杂相互作用所调节的。视觉对人类和其他灵长类动物的重要性反映在大脑皮质中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令人衰弱，不仅源于眼睛的异常，也源于大脑皮层回路的异常。例如，儿童时期的斜视或弱视可能会对处理视觉信息的大脑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皮层(V1)的神经回路的组织和功能，更广泛的目的是了解神经回路如何调节视觉知觉。特别是，这些研究的目的是确定：1)投射到特定纹外视觉皮质区和皮质下结构的V1细胞类型的详细形态特征；2)投射到特定纹外视觉皮质区和皮质下结构的V1神经元的直接局部输入来源；3)通过LGN向V1功能和解剖上不同的隔室提供输入的视网膜神经节细胞类型；以及4)如我们先前和正在进行的体外研究所揭示的那样，单个已识别神经元的体内视觉反应特性如何与这些相同类型细胞的连通性相关。前三个目标将使用首席研究员实验室开发的新型病毒电路跟踪工具来实现。这些工具可以完全填充已识别的投射神经元，并从特定的投射神经元进行单突触限制性跨突触标记。最后一个目的是记录V1神经元的视觉反应，并用染料标记它们，将解剖上不同的细胞类型与功能联系起来。拟议中的研究将提供一个前所未有的视觉皮质回路的视角--他们将揭示视觉皮质神经元的详细连接，以及这些回路如何与组成神经元的功能特性相关。总结：视觉处理的缺陷尤其令人衰弱，不仅是因为眼睛的异常，也是因为皮质回路的异常。拟议中的研究将揭示视觉皮层回路的正常组织和功能，这对于了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.