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R. D. Nobles, U. Muller, M. A. McCall; Glycine Receptor 3 Subunit-Mediated Inhibition in the On and Off Pathways Differentially Contributes to Retinal Ganglion Cell Responses. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4596.
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Glycine and GABA are the primary inhibitory neurotransmitters in the mammalian retina. While the localization of different glycine receptors (GlyRs) in the retina has been examined previously, a lack of subunit specific antagonists has limited the functional analysis of individual receptor-mediated inhibition within the retinal circuit. To this end, we examined visually-evoked responses of retinal ganglion cells (RGC) in a glycine receptor α3 knockout mouse (Glra3-/-).
We characterized the receptive field (RF) properties of RGCs in Glra3-/- mice and C57B6/J wild-type (WT) mice, using in vivo electrophysiological techniques. Mice were anesthetized and tungsten electrodes were used to record the responses of single RGCs from the optic nerve. RF organization was assessed using a series of spots of varying diameter (4.5-52°). Bright spots, for ON- (100 cd/m2), and dark spots, for OFF-center RGCs (3 cd/m2), were presented on a light-adapting background (20 cd/m2). Stimuli were presented 8 times with 2 sec duration and an inter-stimulus interval (ISI) of 5 sec.
The RF organization of ON- and OFF-center RGCs from Glra3-/- and WT mice was characterized and compared at light-adapted levels. Most response properties were not altered by the absence of GlyRα3 expression however, two differences were observed. First, ON-center Glra3-/- RGCs have significantly longer RF center response duration than WT cells. Further, OFF-center Glra3-/- RGCs tend to have less surround antagonism of the RF center response.
Both ON and OFF cone bipolars receive glycinergic inputs via GlyRα3 subunits. Our results suggest that GlyRα3-mediated inhibition subserves different functions in the two cone pathways. In the normal ON pathway, GlyRα3 inputs govern the decay kinetics of the excitatory response, while in the OFF pathway they provide drive to the RF surround.
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