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Varsha Jain, Gautam Awatramani; Inhibitory Control of Starburst Amacrine Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1867.
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© ARVO (1962-2015); The Authors (2016-present)
Directional selectivity (DS) in mammalian retina is first observed at the level of dendrites of GABAergic cholinergic starburst amacrine cells (SACs). Classic studies suggest that acetylcholine release by SACs is controlled by both GABAergic and glycinergic inhibition (Neal and Cunningham, 1995). In mouse retina, the evidence for contribution of glycinergic inputs is mixed. One study demonstrates the presence of glycinergic inputs to ON SACs (Majumdar et al., 2006). In contrast, a more recent study suggests that inhibition to SACs is largely mediated by GABA primarily via GABA receptor alpha 2 (GABARa2 KO; Chen et al., 2016). To reconcile these differences between these physiological findings, here we analysed responses of ON starbursts in various conditions in which different receptors were perturbed, pharmacologically or using genetic KO strategies.
Genetically labelled ON-SACs in the Chat-Cre::Ai9 transgenic mouse line were identified using 2-photon imaging. We used a conditional GABARa2 KO to disrupt GABA inhibition. Using patch clamp techniques, inhibitory post-synaptic currents (IPSCs) were measured in SACs at a holding potential near 0 mV. Responses were evoked by spots or drifting gratings.
Our preliminary data indicates robust inhibitory inputs to starbursts persist in GABARa2 KO mouse model. Inhibition had sustained and transient components. Interestingly, when probed with gratings of different spatial and temporal frequencies, we found that the overall tuning of inhibition was changed in the a2KO mice compared to wild-type mice. Moreover, application of TTX (which blocks spike activity) and strychnine (glycine receptor antagonist) affected the tuning properties of inhibition in a complex way. This suggests spiking amacrine cells such as WACs, and glycinergic amacrine cells cooperatively interact to shape SAC responses via reciprocal inhibition, in a stimulus dependent manner.
These results suggest that inhibition at ON-SACs is more complex than previously envisioned. It likely involves multiple GABA receptor types (in addition to GABARa2) as well as inputs from multiple amacrine cell types.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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