Dissecting a microcircuit that regulates the earliest light responses in the retina

University Of California Berkeley, Berkeley CA

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Abstract

-Project Summary- In the retina, a subset of retinal ganglion cells (RGCs) are intrinsically photosensitive (ipRGCs) because they express a light-sensitive pigment called melanopsin. IpRGCs can therefore encode ambient light intensity without input from rod and cone photoreceptors. During retinal development, ipRGCs are the sole source of light-evoked activity in the retina before rod and cone photoreceptors mature. IpRGCs are necessary for multiple behaviors in neonatal animals, including the pupillary light reflex, light aversion, and light entrainment of sleep/wake cycles. Mounting evidence indicates that ipRGCs are electrically coupled through gap junctions. Additionally, a recent study in our lab suggests that dopamine signaling in the retina regulates the strength of electrical coupling in this circuit. In this proposal, we explore the hypothesis that dopaminergic modulation of electrical coupling between ipRGCs influences the light sensitivity of ipRGCs and of the behaviors that they evoke. There are multiple types of ipRGCs in the retina, which mediate distinct behaviors. As a first step toward understanding the function of electrical coupling between ipRGCs, we propose in Aim 1 to use a circuit mapping technique to identify which ipRGC types participate in electrical coupling. Using calcium imaging, we will then determine if electrical coupling between specific types of ipRGCs enhances their sensitivity to light. To determine how dopamine signaling modulates electrical coupling between ipRGCs, we will use an intersectional transgenic strategy to knock out dopamine receptors specifically in ipRGCs. We will then use electrophysiology experiments to determine if dopamine signaling decreases the strength of electrical coupling between ipRGCs. In Aim 2, we propose to use behavioral tests to determine if the strength of electrical coupling between ipRGCs modulates the light sensitivity of the behaviors they mediate.