Glycinergic inhibition suppresses ON but not ON-OFF direction-selective retinal ganglion cells

Abstract

Purpose : Two classes of direction-selective ganglion cells (DSGCs) in the mammalian retina operate over different velocity ranges: ON DSGCs respond to slow movement and may code for global image displacement produced by self-motion, while ON-OFF DSGCs respond to faster image velocities and are selective for local motion produced by external objects. While these two classes share common circuitry, little is known about the mechanisms that underlie the differences in velocity tuning.

Methods : Pairs of ON and ON-OFF DSGCs in rabbit retina were chosen to have overlapping receptive fields. Synaptic currents and potentials were recorded while presenting moving and sinusoidal flicker stimuli. Synaptic inputs to the two types were identified by bath applying the GABA_A receptor antagonist SR95531 (10 µM), the GABA_C receptor antagonist TPMPA (100 µM), and the glycine receptor antagonist strychnine (0.5 µM).

Results : We observed different patterns of inhibitory inputs in the two types of DSGCs during sinusoidal flickering light stimuli; large, transient IPSPs seen in ON DSGCs were not present in the overlapping ON-OFF DSGCs (n = 3 pairs, IPSP amplitude -6.0 ± 1.8 mV, t-peak 8.6 ± 3.7 ms, t- decay 20 ± 7.9 ms, n = 11 ON DSGCs). Bath application of strychnine suppressed IPSPs recorded early in the stimulus cycle (-12 ± -4 to -1 ± -2 mV, p < 0.005, n = 4) and increased the spike output of ON DSGCs. Inhibitory and excitatory conductances were estimated by analysis of light-evoked synaptic currents. Co-application of SR95531 and TPMPA decreased but did not completely block the inhibitory conductance in ON DSGCs (n=3). The remaining transient inhibitory input was abolished by strychnine (n = 2). Strychnine suppressed inhibition in ON DSGCs more strongly at high than low flicker frequencies (74.5 ± 6% vs 40.7 ± 16.4%, p < 0.05, n= 5). Consistent with previous findings, SR95531 alone completely abolished the inhibitory conductance in ON-OFF DSGCs (n = 2).

Conclusions : ON DSGCs, but not ON-OFF DSGCs, receive transient glycinergic inhibitory inputs that are activated selectively at high flicker frequencies. The results suggest that glycinergic inhibition may contribute to the differences in velocity tuning between the two main classes of DSGCs in the mammalian retina.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.