Receptor and transmitter release properties set the time course of retinal inhibition

Synaptic inhibition is determined by the properties of postsynaptic receptors, neurotransmitter release, and clearance, but little is known about how these factors shape sensation-evoked inhibition. The retina is an ideal system to investigate inhibition because it can be activated physiologically with light, and separate inhibitory pathways can be assayed by recording from rod bipolar cells that possess distinct glycine, GABA_A, and GABA _C receptors (R). We show that receptor properties differentially shape spontaneous IPSCs, whereas both transmitter release and receptor properties shape light-evoked (L) IPSCs. GABA_CR-mediated IPSCs decayed the slowest, whereas glycineR- and GABA_AR-mediated IPSCs decayed more rapidly. Slow GABA_CRs determined the L-IPSC decay, whereas GABA_ARs and glycineRs, which mediated rapid onset responses, determined the start of the L-IPSC. Both fast and slow inhibitory inputs distinctly shaped the output of rod bipolar cells. The slow GABA_CRs truncated glutamate release, making the A17 amacrine cell L-EPSCs more transient, whereas the fast GABA_AR and glycineRs reduced the initial phase of glutamate release, limiting the peak amplitude of the L-EPSC. Estimates of transmitter release time courses suggested that glycine release was more prolonged than GABA release. The time course of GABA release activating GABA_CRs was slower than that activating GABA_ARs, consistent with spillover activation of GABA_CRs. Thus, both postsynaptic receptor and transmitter release properties shape light-evoked inhibition in retina.