Photoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina

Area of Science:

• Neuroscience
• Retinal Physiology
• Cellular Biology

Background:

• Intrinsically photosensitive retinal ganglion cells (ipRGCs) possess melanopsin for light detection, independent of rods and cones.
• ipRGCs communicate with intraretinal circuitry through electrical synapses with amacrine cells (ACs), but their targets and functions are poorly understood.

Purpose of the Study:

• To identify the specific retinal circuitry and functional roles of electrical synapses formed by ipRGCs with amacrine cells.
• To investigate the contribution of melanopsin-expressing ipRGCs to intraretinal signaling.

Main Methods:

• Utilized whole-cell recordings in mice during pharmacological blockade of rod and cone input.
• Performed optogenetic stimulation of specific amacrine cell types.
• Examined anatomical and physiological coupling between ipRGC subtypes and amacrine cells.

Main Results:

• Identified M5 ipRGCs forming electrical synapses with corticotropin-releasing hormone-expressing (CRH+) ACs, a nonspiking GABAergic interneuron.
• Demonstrated that CRH+ ACs mediate persistent visual responses in ipRGCs, dependent on melanopsin and gap junctions.
• Showed that CRH+ ACs inhibit specific ipRGC types (M4, M5) and influence other ipRGC-coupled ACs, indicating network interactions.

Conclusions:

• Established a functional circuit where ipRGCs, particularly M5, signal through electrical synapses to CRH+ ACs, leading to local inhibition of retinal neurons.
• Highlighted the role of ipRGC-AC electrical synapses in modulating retinal circuit output, especially in mature retinas.
• Revealed that ipRGCs can influence retinal processing via both anterograde brain signaling and retrograde intraretinal signaling through amacrine cell networks.