Functional subtypes of retinal ganglion cell photoreceptors

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Project Summary The retina conveys visual information to the brain through retinal ganglion cells whose axons make up the optic nerve. There are many different types of retinal ganglion cells that in parallel convey a different component of vision, such as detail, color, direction, or intensity. Most retinal ganglion cells receive a processed version photoreceptor output, through synapses in the retina. Some retinal ganglion cells contain their own photopigment (melanopsin) and respond directly to light. Intrinsically photosensitive retinal ganglion cells (ipRGCs) send their axons to at least 16 distinct central brain regions and influence a wide range of behaviors such as circadian entrainment and pupil reflex, sleep, body temperature, and mood. This proposal seeks to examine functional subtypes of ipRGCs, their location and density in the retina, and the light response properties that differentiate functional groups. Preliminary data indicates some ipRGC types can be divided into functional subtypes based on their mosaic spacing and the expression of unique mRNA, and Cre. We hypothesize ipRGC subtypes are restricted to sub-regions of retina and ipRGCs within these subtypes differ in their anatomical spacing, the neurotransmitters they release at central synapses, and the specific light stimuli they respond to. We have identified unique subtypes of ipRGCs with restricted to the dorsal retina that express inhibitory proteins and are spaced evenly across the retina, indicating they align in functional groups. In this proposal, we will map the locations of individual ipRGC subtypes across the entire retina to build a spatial map of their dendrites and how they overlap with each other. We will test ipRGCs for unique mRNA expression patterns and use central brain injections to label them from distinct brain regions and estimate the total number of ipRGC subtypes. We will use multielectrode array recordings to record from thousands of ipRGCs in response to a detailed array of light stimuli and use unbiased cluster analysis to define their functional groups.