Abstract
Purpose :
In the retina, diverse types of GABAergic and glycinergic amacrine cells work together to enable specific circuits to extract features from the visual environment. Identifying their roles within a given circuit, however, remains a central challenge. One circuit in which much progress has been made is the mouse direction-selective (DS) circuit. Here, starburst amacrine cells (SACs) provide DS GABAergic inhibition which endows upon ganglion cell to encode direction. Wide-field amacrine cells (WACs) on the other hand provide a feedback surround inhibition to excitatory bipolar cells and endows the circuit with size selectivity. A third amacrine cell type, glycinergic narrow-field amacrine cells (NACs) has also been recently shown to make few anatomic connections to On SACs (Ding et al., 2016). Here, we investigate the role of this glycinergic inhibition in the DS circuit.
Methods :
ON SACs and superior coding DSGCs were identified using 2-photon imaging in the Chat-Cre::Ai9 and Hb9::eGFP transgenic mouse lines respectively. Inhibitory post-synaptic currents (IPSCs) were measured in SACs and DSGCs at a holding potential near 0 mV, using patch clamp techniques. Responses were evoked by drifting spots or gratings of different spatiotemoral frequencies.
Results :
Based on the kinetics and pharmacological properties of IPSCs measured in ON SACs we identified at least three distinct types of inhibition. A transient TTX-sensitive GABAergic inhibition, suggesting that it was mediated by WACs. A TTX-insensitive transient GABAergic IPSC, presumably mediated by neighbouring SACs. And thirdly, a strong sustained glycinergic inhibition at both the light onset and offset, likely mediated by NACs. Glycinergic inputs were intact in mice in which SAC GABA transmission was genetically deleted (Chat-Cre:: gabra2 or Chat-Cre: VGAT KO). Owing to its delayed temporal kinetics, the effects of glycinergic inhibition were only apparent at certain spatiotemporal frequencies. Interestingly at these frequencies, blocking glycine receptors reveal SAC GABAergic output that is non-directional.
Conclusions :
These results indicate that glycinergic NACs serve as checkpoints in the DS circuit, preventing neurotransmitter release from ON SACs under non-optimal stimulus conditions. They add to our understanding of how three distinct amacrine cells endow a single retinal circuit the ability to robustly encode direction under diverse stimulus conditions.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.