Connecting developmental mechanisms to visual function and perception

描述（由申请人提供） 翻译后摘要：在发展过程中，细胞的过程，如神经突的生长和突触的形成雕刻的大脑的连接。在视觉皮层中，这导致了功能性神经回路，使我们能够看到和理解周围的世界。神经发育和视觉加工的分离研究取得了重大进展。然而，要将这两个方面联系起来，理解视觉系统如何连接起来，以创建视觉基础的特定感受野特性，就更加困难了。事实上，我们仍然不知道产生方向选择性的发育机制，初级视觉皮层的基本反应特性。解决这个问题需要一种方法，可以将分子和细胞发育与系统视觉神经科学联系起来。我以前的工作表明，小鼠视觉皮层是研究视觉处理的有效模型，我最近建立了一些创新技术，使我们能够研究小鼠视觉系统，从单个基因和细胞类型到视觉处理和感知。在这里，我提出了一个综合的方法，我将应用分子遗传学技术来操纵关键的发育途径和神经元的特定子集的神经活动，使用体内成像来评估视觉反应特性和细胞生长和突触发生的影响，并进行行为心理物理学测试对视觉感知的影响。这些研究将为神经回路的组装提供重要的见解，神经回路是正常大脑功能和许多发育障碍的基础。 公共卫生相关性：该项目涉及视觉系统中功能回路的组装，因此将对导致失明或视力障碍的疾病状态的研究产生直接影响。此外，作为一个一般的方法来阐明皮质发育的原则，我们的方法应广泛适用于一些发育障碍，如阅读障碍，自闭症和精神分裂症，这被认为是由于异常的皮质布线和功能。

DESCRIPTION (Provided by the applicant) Abstract: During development, cellular processes such as neurite growth and synapse formation sculpt the connectivity of the brain. In the visual cortex, this results in functional neral circuits that allow us to see and understand the world around us. Significant progress has been made in studying neural development and visual processing separately. However, it has been more difficult to link these two aspects into an understanding of how the visual system wires itself up to create the specific receptive field properties that underlie vision. Indeed, we still o not know the developmental mechanisms that create orientation selectivity, the fundamental response property of primary visual cortex. Answering this question requires an approach that can bridge molecular and cellular development with systems visual neuroscience. My previous work demonstrated that the mouse visual cortex is an effective model for studying visual processing, and I have recently established a number of innovative techniques allowing us to study the mouse visual system from single genes and cell types up to visual processing and perception. Here I propose an integrative approach, in which I will apply molecular genetic techniques to manipulate key developmental pathways and neural activity in specific subsets of neurons, use in vivo imaging to assess the impact on both visual response properties and cellular growth and synaptogenesis, and perform behavioral psychophysics to test the effects on visual perception. These studies will provide important insight into the assembly of neural circuits, which underlies both normal brain function as well as numerous developmental disorders. Public Health Relevance: This project addresses the assembly of functional circuits in the visual system, and thus will have direct impact on studies of disease states resulting in blindness or visual impairment. Furthermore, as a general method to elucidate principles of cortical development, our approach should be broadly applicable to a number of developmental disorders, such as dyslexia, autism, and schizophrenia, which are thought to result from aberrant cortical wiring and function.