Visual Signal Transformation in the Retinocollicular Pathway

 描述(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中的明显重要性和可用的遗传工具，小鼠上丘(SC)在理解视觉信号转换及其机制方面具有很大的希望。SC是一种分层结构，对于多模式整合和感觉运动转换很重要，其表层是纯视觉的，接受来自视网膜的直接视网膜输入。在他的建议中，研究人员将研究视网膜小球通路中发生的重要变化背后的大脑电路和突触机制，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。这些实验将确定在表层SC中是否存在深度、区域和/或细胞类型特定的方向选择性组织，从而为以下目标奠定基础。其次，研究人员将确定投射到SC的视网膜输入的反应特性。基因编码的钙指示剂将在视网膜神经节细胞中表达，并将进行双光子成像，以显示它们在丘脑中的轴突终末。第三，视网膜终末和视丘神经元的成像方法将用于视网膜睫状体投射在空间上发生改变的转基因小鼠中，以确定方向选择性视网膜输入是否需要在THSC中进行方向选择性。最后，研究人员将进行活体全细胞记录，以研究SC中的视觉诱发反应。这些实验将在转基因小鼠身上进行，在转基因小鼠中，兴奋性SC神经元可以通过光遗传刺激沉默，从而将视网膜输入暴露在记录的细胞中。通过比较总的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延髓通路中处理和转换方向选择性的突触机制。总而言之，这些实验将产生全面了解大脑视觉处理所需的重要数据。由于一些神经和精神障碍，如阅读障碍、精神分裂症和自闭症谱系障碍，正常的视觉加工会受到影响，这些研究将为理解和治疗这些障碍提供洞察力。

 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.