title: Parallel Inhibition of Dopamine Amacrine Cells and Intrinsically Photosensitive Retinal Ganglion Cells in a Non-Image-Forming Visual Circuit of the Mouse Retina.
abstract: An inner retinal microcircuit composed of dopamine (DA)-containing amacrine cells and melanopsin-containing, intrinsically photosensitive retinal ganglion cells (M1 ipRGCs) process information about the duration and intensity of light exposures, mediating light adaptation, circadian entrainment, pupillary reflexes, and other aspects of non-image-forming vision. The neural interaction is reciprocal: M1 ipRGCs excite DA amacrine cells, and these, in turn, feed inhibition back onto M1 ipRGCs. We found that the neuropeptide somatostatin [somatotropin release inhibiting factor (SRIF)] also inhibits the intrinsic light response of M1 ipRGCs and postulated that, to tune the bidirectional interaction of M1 ipRGCs and DA amacrine cells, SRIF amacrine cells would provide inhibitory modulation to both cell types. SRIF amacrine cells, DA amacrine cells, and M1 ipRGCs form numerous contacts. DA amacrine cells and M1 ipRGCs express the SRIF receptor subtypes sst(2A) and sst4 respectively. SRIF modulation of the microcircuit was investigated with targeted patch-clamp recordings of DA amacrine cells in TH-RFP mice and M1 ipRGCs in OPN4-EGFP mice. SRIF increases K(+) currents, decreases Ca(2+) currents, and inhibits spike activity in both cell types, actions reproduced by the selective sst(2A) agonist L-054,264 (N-[(1R)-2-[[[(1S*,3R*)-3-(aminomethyl)cyclohexyl]methyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]spiro[1H-indene-1,4'-piperidine]-1'-carboxamide) in DA amacrine cells and the selective sst4 agonist L-803,087 (N(2)-[4-(5,7-difluoro-2-phenyl-1H-indol-3-yl)-1-oxobutyl]-L-arginine methyl ester trifluoroacetate) in M1 ipRGCs. These parallel actions of SRIF may serve to counteract the disinhibition of M1 ipRGCs caused by SRIF inhibition of DA amacrine cells. This allows the actions of SRIF on DA amacrine cells to proceed with adjusting retinal DA levels without destabilizing light responses by M1 ipRGCs, which project to non-image-forming targets in the brain.
authors.affiliation: Departments of Neurobiology and Molecular, Cellular, and Integrative Physiology, Stein Eye Institute, and.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Vuong
authors.affiliation: Departments of Neurobiology and.
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Hardi
authors.affiliation: Departments of Neurobiology and Departments of Physiology and Biophysics and Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada, and Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073.
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Departments of Neurobiology and Molecular, Cellular, and Integrative Physiology, Stein Eye Institute, and CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California 90095, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073 nbrecha@ucla.edu.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects / Q000502:physiology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010775:Photic Stimulation; D010880:Piperidines / Q000494:pharmacology; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D000577:Amides; D002118:Calcium; D004298:Dopamine; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D007211:Indoles; D009419:Nerve Tissue Proteins; D010880:Piperidines; D017299:Rod Opsins; D013004:Somatostatin; D000099210:Melanopsin; C112853:L 54264; C429628:L803087
keywords: amacrine cells; dopamine; interneuron; melanopsin ipRGCs; microcircuit; somatostatin