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, GABAA receptor subunit α2 (GABAAR 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, GABAAR 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 GABAAR 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 GABAARs 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.
Highlights
One of many neural computations performed by the retina is direction selectivity (DS), with certain types of retinal ganglion cells (RGCs) tuned to specific directions of image motion
Using immunostaining and confocal microscopy, we show that GABAAR a2 clusters in the inner plexiform layer (IPL) of the rabbit and mouse retinae are concentrated in distinct strata, which correspond to the dendritic plexuses of starburst amacrine cells (SACs) and Direction-selective ganglion cells (DSGCs)
Of all GABAA receptor subunits reported in the retina, only a2 and d aggregate within the two IPL bands that can be labeled with antibodies against choline acetyl transferase (ChAT)
Summary
One of many neural computations performed by the retina is direction selectivity (DS), with certain types of retinal ganglion cells (RGCs) tuned to specific directions of image motion. Direction-selective ganglion cells (DSGCs) were first systematically studied in the rabbit several decades ago [1]. Most classical DSGCs have rather symmetrical dendritic arbors that do not necessarily correlate with the cell’s preferred motion direction (but see [15]). These DGSCs rely mainly on spatially asymmetric inhibition from GABAergic interneurons, the starburst amacrine cells (SACs; for review see [16,17,18]), which generate local DS signals within their dendrites [19,20,21]. Classical DSGCs may contain a subpopulation with more pronounced asymmetrical dendritic arbors, shown to contribute to DS responses, at least for lower motion velocities [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
