期刊
JOURNAL OF NEUROSCIENCE
卷 41, 期 7, 页码 1489-1504出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0674-20.2020
关键词
amacrine cell; corticotropin releasing hormone; gap junction; ipRGC; melanopsin; retinal ganglion cell
资金
- National Institutes of Health [EY014454, EY021372, P30 EY026878, T32 NS041228, T32 EY022312]
- National Science Foundation Graduate Research Fellowship
- Gruber Science Fellowship
In this study, a circuitry was identified in mice that allows M5 ipRGCs to locally inhibit retinal neurons by forming electrical synapses with nonspiking GABAergic amacrine cells. The results demonstrate a functional role for electrical synapses in translating ipRGC activity into feedforward and feedback inhibition of local retinal circuits.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit melanopsin-dependent light responses that persist in the absence of rod and cone photoreceptor-mediated input. In addition to signaling anterogradely to the brain, ipRGCs signal retrogradely to intraretinal circuitry via gap junction-mediated electrical synapses with amacrine cells (ACs). However, the targets and functions of these intraretinal signals remain largely unknown. Here, in mice of both sexes, we identify circuitry that enables M5 ipRGCs to locally inhibit retinal neurons via electrical synapses with a nonspiking GABAergic AC. During pharmacological blockade of rodand cone-mediated input, whole-cell recordings of corticotropin-releasing hormone-expressing (CRH+) ACs reveal persistent visual responses that require both melanopsin expression and gap junctions. In the developing retina, ipRGC-mediated input to CRH+ ACs is weak or absent before eye opening, indicating a primary role for this input in the mature retina (i.e., in parallel with rodand cone-mediated input). Among several ipRGC types, only M5 ipRGCs exhibit consistent anatomical and physiological coupling to CRH+ ACs. Optogenetic stimulation of local CRH+ ACs directly drives IPSCs in M4 and M5, but not M1-M3, ipRGCs. CRH+ ACs also inhibit M2 ipRGC-coupled spiking ACs, demonstrating direct interaction between discrete networks of ipRGC-coupled interneurons. Together, these results demonstrate a functional role for electrical synapses in translating ipRGC activity into feedforward and feedback inhibition of local retinal circuits.
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