Parallel inhibition of dopamine amacrine cells and intrinsically photosensitive retinal ganglion cells in a non-image-forming visual circuit of the mouse retina

Helen E. Vuong, Claudia N. Hardi, Steven Barnes, Nicholas C. Brecha

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 sst2A 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 Ca2+ currents, and inhibits spike activity in both cell types, actionsreproduced by the selective sst2AagonistL-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 (N2-[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.

Original languageEnglish (US)
Pages (from-to)15955-15970
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number48
DOIs
StatePublished - Dec 2 2015

Bibliographical note

Publisher Copyright:
©2015 the authors.

Keywords

  • Amacrine cells
  • Dopamine
  • Interneuron
  • Melanopsin ipRGCs
  • Microcircuit
  • Somatostatin

Fingerprint

Dive into the research topics of 'Parallel inhibition of dopamine amacrine cells and intrinsically photosensitive retinal ganglion cells in a non-image-forming visual circuit of the mouse retina'. Together they form a unique fingerprint.

Cite this