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Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses.

ABSTRACT: Extracellular and whole-cell light-evoked responses of mouse retinal ganglion cells were recorded in the presence of the mGluR8 selective agonist, (S)-3,4-dicarboxy-phenylglycine (DCPG). Off-light responses were reversibly reduced in the presence of DCPG in wild-type but not in mGluR8-deficient retinas. On-responses were only marginally modulated by DCPG. During Off-responses, DCPG suppressed both excitatory and inhibitory synaptic conductances suggesting that mGluR8 receptor activity reduces glutamate release from bipolar cell terminals and possibly also the release of an inhibitory neurotransmitter from amacrine cell processes.

SUBMITTER: Quraishi S

PROVIDER: S-EPMC2837113 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses.

Quraishi S S Reed B T BT Duvoisin R M RM Taylor W R WR

Neuroscience 20100120 3

Extracellular and whole-cell light-evoked responses of mouse retinal ganglion cells were recorded in the presence of the mGluR8 selective agonist, (S)-3,4-dicarboxy-phenylglycine (DCPG). Off-light responses were reversibly reduced in the presence of DCPG in wild-type but not in mGluR8-deficient retinas. On-responses were only marginally modulated by DCPG. During Off-responses, DCPG suppressed both excitatory and inhibitory synaptic conductances suggesting that mGluR8 receptor activity reduces gl ...[more]

PMID: 20096339

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Project description:A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ([Ca2+]i) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input. Light induced a rise in [Ca2+]i (monitored using fura-2 imaging) in the immunopanned ipRGCs and the source of this Ca2+ signal was investigated. The Ca2+ responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1-2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic acid, lanthanum, and gadolinium, consistent with the involvement of canonical transient receptor potential (TRP) channels in ipRGC phototransduction. However, the contribution of direct Ca2+ flux through a putative TRP channel to ipRGC [Ca2+]i was relatively small, as most (approximately 90%) of the light-induced Ca2+ responses could be blocked by preventing action potential firing with tetrodotoxin. The L-type voltage-gated Ca2+ channel (VGCC) blockers verapamil and (+)-cis-diltiazem significantly reduced the light-evoked Ca2+ responses, while the internal Ca2+ stores depleting agent thapsigargin had negligible effect. These results indicate that Ca2+ influx through VGCCs, activated after action potential firing, was the primary source for light-evoked elevations in ipRGC [Ca2+]i. Furthermore, concurrent Ca2+ imaging and cell-attached electrophysiological recordings demonstrated that the Ca2+ responses were highly correlated to spike frequency, thereby establishing a direct link between action potential firing and somatic [Ca2+]i in light-stimulated ipRGCs.

Dataset Information

Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses.

Publications

Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses.

Similar Datasets

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