GABA a receptors containing the α2 subunit are critical for direction-selective inhibition in the retina

Olivia Nicola Auferkorte, Tom Baden, Sanjeev Kumar Kaushalya, Nawal Zabouri, Uwe Rudolph, Silke Haverkamp, Thomas Euler

Research output: Contribution to journalArticle

Abstract

Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS) retinal circuits include several subtypes of ganglion cells (GCs) and inhibitory interneurons, such as starburst amacrine cells (SACs). Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL) of mouse and rabbit retina, GABA A receptor subunit α2 (GABA AR α2) aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABA AR α2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABA AR α2 knock-out (KO) mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that α2-containing GABA ARs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit.

Original languageEnglish (US)
Article numbere35109
JournalPloS one
Volume7
Issue number4
DOIs
StatePublished - Apr 10 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Auferkorte, O. N., Baden, T., Kaushalya, S. K., Zabouri, N., Rudolph, U., Haverkamp, S., & Euler, T. (2012). GABA a receptors containing the α2 subunit are critical for direction-selective inhibition in the retina. PloS one, 7(4), [e35109]. https://doi.org/10.1371/journal.pone.0035109