Inhibitory inputs to an inhibitory interneuron: Spontaneous postsynaptic currents and GABA_A receptors of A17 amacrine cells in the rat retina

Abstract

Amacrine cells constitute a large and heterogeneous group of inhibitory interneurons in the retina. The A17 amacrine plays an important role for visual signalling in the rod pathway microcircuit of the mammalian retina. It receives excitatory input from rod bipolar cells and provides feedback inhibition to the same cells. However, from ultrastructural investigations, there is evidence for input to A17s from other types of amacrine cells, presumably inhibitory, but there is a lack of information about the identity and functional properties of the synaptic receptors and how inhibition contributes to the integrative properties of A17s. Here, we studied the biophysical and pharmacological properties of GABAergic spontaneous inhibitory postsynaptic currents (spIPSCs) and GABA_A receptors of A17 amacrines using whole-cell and outside-out patch recordings from rat retinal slices. The spIPSCs displayed fast onsets (10%–90% rise time ~740 μs) and double-exponential decays (τ_fast ~4.5 ms [43% of amplitude]; τ_slow ~22 ms). Ultra-fast application of brief pulses of GABA (3 mM) to patches evoked responses with deactivation kinetics best fitted by a triple-exponential function (τ1 ~5.3 ms [55% of amplitude]; τ2 ~48 ms [32% of amplitude]; τ3 ~187 ms). Non-stationary noise analysis of spIPSCs and patch responses yielded single-channel conductances of ~21 and ~25 pS, respectively. Pharmacological analysis suggested that the spIPSCs are mediated by receptors with an α1βγ2 subunit composition and the somatic receptors have an α2βγ2 and/or α3βγ2 composition. These results demonstrate the presence of synaptic GABA_A receptors on A17s, which may play an important role in signal integration in these cells.