Visual Signal Transformation in the Retinocollicular Pathway

 描述（由申请人提供）：视觉信息如何在神经系统中处理和转换是视觉研究中的一个基本问题。鉴于其在视觉引导行为和可用的遗传工具中的明显重要性，小鼠上级丘（SC）对于理解视觉信号转换及其机制具有很大的希望。SC是一种分层结构，对于多模态整合和感觉运动转换很重要，其表层是纯视觉的，并接收来自视网膜的直接视网膜定位输入。在他的提议中，研究人员将研究视网膜丘通路中发生的重要转变的脑回路和突触机制，特别是运动方向的处理。首先，将进行双光子钙成像以确定单个SC神经元的方向选择性及其空间组织。这些实验将建立是否有一个深度，区域，和/或细胞类型特异性组织的方向选择性在表面SC，从而形成了以下目标的基础。其次，研究人员将确定投射到SC的视网膜输入的响应特性。遗传编码的钙指标将在视网膜神经节细胞中表达，并将进行双光子成像以可视化丘中的轴突终末。第三，成像视网膜终末和丘神经元的方法将用于其中视网膜丘投射在空间上改变的转基因小鼠系中，以确定SC中的方向选择性是否需要方向选择性视网膜输入。最后，研究者将进行体内全细胞记录，以目视研究-这些实验将在转基因小鼠中进行，其中兴奋性SC神经元可以通过光遗传学刺激沉默，从而将视网膜输入暴露于记录的细胞。通过比较总输入和视网膜输入对单个SC神经元的选择性，这些实验将开始揭示视网膜丘通路中方向选择性加工和转化的突触机制。 总之，这些实验将产生完整理解大脑视觉处理所需的重要数据。由于正常的视觉处理在一些神经和精神疾病中受到损害，例如阅读障碍，精神分裂症和自闭症谱系障碍，这些研究将为理解和治疗这些疾病提供见解。

 DESCRIPTION (provided by applicant): How visual information is processed and transformed in the nervous system is a fundamental question in vision research. Given its clear importance in visually-guided behaviors and the available genetic tools, the mouse superior colliculus (SC) holds great promise for understanding visual signal transformation and its mechanisms. The SC is a layered structure important for multimodal integration and sensorimotor transformation, and its superficial layers are purely visual and receive direct retinotopic inputs from the retina. In his proposal, the investigators will study the brain circuitry and synaptic mechanisms underlying the important transformations that take place in the retinocollicular pathway, especially the processing of motion direction. First, 2-photon calcium imaging will be performed to determine the direction selectivity of individual SC neurons and their spatial organization. These experiments will establish whether there is a depth-, region-, and/or cell type-specific organization of direction selectivity in the superficial SC, thereby forming a foundation for the following aims. Second, the investigators will determine the response properties of the retinal input that project to the SC. Genetically-encoded calcium indicators will be expressed in retinal ganglion cells and 2- photon imaging will be performed to visualize their axonal terminals in the colliculus. Third, the methods of imaging retinal terminals and collicular neurons will be used in a line of transgenic mice where retinocollicular projections are spatially altered, in order to determine whether direction selective retinal input is required for the direction selectivity in th SC. Finally, the investigator will perform in vivo whole cell recording to study visually-evoked responses in the SC. These experiments will be performed in transgenic mice where excitatory SC neurons can be silenced by optogenetic stimulation, thereby exposing the retinal input to the recorded cells. By comparing the selectivity of the total and retinal input to individual SC neurons, these experiments will start to reveal the synaptic mechanisms underlying the processing and transformation of direction selectivity in the retinocollicular pathway. Together, these experiments will generate important data needed for a complete understanding of visual processing in the brain. Because normal visual processing is compromised in a number of neurological and psychiatric disorders, such as dyslexia, schizophrenia and autism spectrum disorders, these studies will provide insights for the understanding and treatment of these disorders.