Molecular Specification of Direction Selectivity in the Visual System

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DESCRIPTION (provided by applicant): Orderly neural circuits underlie processing of information in the nervous system: our perceptions, decisions and behaviors. A main goal of neurobiology is to understand how the circuits form. We use the retina to address this issue. Distinct types of retinal ganglion cells respond to different visual features, based on which inputs they receive from retinal interneurons. Several types are direction selective, responding best to objects moving in a particular direction. The mammalian retina contains at least 3 types of direction selective ganglion cells (DSGCs). However, the lack of molecular markers to selectively identify DSGCs has impeded analysis of their development, synaptic inputs in the retina, and targets in the brain. We have now found markers for 3 types of DSGCs and developed transgenic approaches to label each type in vivo. This method allows us to elucidate molecular mechanisms that regulate differentiation of these neurons, and to trace the neuronal circuits that initiate responses to moving objects. In specific aims 1-3, we will characterize mice in which each DSGC type is specifically labeled. We will analyze the morphological and functional development of each DSGC type, and seek roles of the subtype specific genes (an adhesion molecule, JAM-B and two secreted molecules, FSTL4 and SPIG1/FSTL5) in these processes. In specific aim 4, we will use transsynaptic tracers to define the connections of each DSGC type. Finally (specific aim 5), we will seek new molecules that regulate diverse aspects of DSGC development. Together, these studies will provide novel insights into the cellular basis of visual processing. Following the mentored period in the Center for Brain Science at Harvard University, I will start my own lab as an independent investigator at an academic institution. My long-term goal is to study how neural circuits are formed and modified by experience. I hope that my work will provide insights in studying how neural circuit fails in psychiatric diseases.