Genetic Manipulation of Retinal Ganglion Cell Subtypes

Light is a profoundly important regulator of physiology and behavior across a wide range of organisms. Light information is relayed via diverse retinal ganglion cell types to approximately 50 distinct targets in the brain. The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent 6 of the 40 retinal ganglion cell types present in the mouse retina. The M1-M6 ipRGC subtypes each possess a distinct complement of morphological and physiological features, central projections, and behavioral roles. Thus, mapping of ipRGC circuits with single subtype resolution would provide critical insight into the function of multiple and varied visual circuits. However, progress on this front has been hampered by a dearth of genetic tools for label, manipulation, and ablation of single subtypes of retinal ganglion cell. Our preliminary data indicate that a Cre and Flp-based intersectional approach could allow for such manipulation of single ipRGC subtypes. This proposal aims to identify genetic marker combinations unique to single ipRGC subtypes. Additionally, we will simultaneously create a modular genetic toolkit that can be integrated into any Cre/Flp motif for future ipRGC subtype manipulation. These tools will not only provide immediate insight into ipRGC-connected circuits, but will provide critical tools and an experimental pipeline for the visual and circuit neuroscience communities to study a broad range of circuits to link cellular function to behavior.