Receptor and Transmitter Release Properties Set the Time Course of Retinal Inhibition

Abstract

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 C R-mediated IPSCs decayed the slowest, whereas glycineR-and GABA A R-mediated IPSCs decayed more rapidly. Slow GABA C Rs determined the L-IPSC decay, whereas GABA A Rs 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 C Rs truncated glutamate release, making the A17 amacrine cell L-EPSCs more transient, whereas the fast GABA A R 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 C Rs was slower than that activating GABA A Rs, consistent with spillover activation of GABA C Rs. Thus, both postsynaptic receptor and transmitter release properties shape light-evoked inhibition in retina.

Patch-Clamp Investigations and Compartmental Modeling of Rod Bipolar Axon Terminals in an In Vitro Thin-Slice Preparation of the Mammalian Retina

“…Unless corrected for, the stronger attenuation of peak amplitude of IPSCs in soma-end recordings will lead to an underestimation of the number of channels open at the peak of the IPSCs (see review by Silver and Farrant 1999). Our simulations and observations are supported by the fast rise times of spIPSCs recorded in isolated axon terminals of goldfish bipolar cells (0.29 ms) (Palmer 2006) compared with the slower rise times of spIPSCs in soma-end recordings from mouse bipolar cells (0.9 -1.2 ms) (Eggers and Lukasiewicz 2006;Frech and Backus 2004;Ivanova et al 2006).…”

“…The time constant of decay ( decay ) was 1, 5, or 10 ms. This covered the relevant range of values for decay observed in our own terminal-end recordings of spIPSCs (unpublished results), in soma-end recordings of spIPSCs from mouse rod bipolar cells (Eggers and Lukasiewicz 2006;Frech and Backus 2004;Ivanova et al 2006), and in isolated terminal recordings of spIPSCs from goldfish bipolar cells (Palmer 2006). The conductance waveforms were injected at the axon terminal in our idealized model of a rod bipolar cell, voltage-clamped either at the soma end or the terminal end (Fig.…”

“…They appeared as transient inward currents (at a holding potential of Ϫ60 mV) with very fast rise times (Ͻ400 s; see following text) and slower decays. The spontaneous PSCs were inward at a holding potential of Ϫ60 mV and were reversibly blocked by a mixture of GABA A (bicuculline), GABA C (TPMPA), and glycine (strychnine) receptor antagonists (data not shown), suggesting that they are spontaneous, inhibitory PSCs (spIPSCs) generated by release of GABA and/or glycine from amacrine cell processes contacting the axon and axon terminals of rod bipolar cells (Cui et al 2003;Eggers and Lukasiewicz 2006;Frech and Backus 2004;Ivanova et al 2006). Similar spontaneous PSCs were seen in a total of 15 axon terminal recordings.…”

ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina

“…Two non-exclusive functional implications arise. First, glycine receptor (glyR)-mediated, GABA receptor (GABAR)-mediated inhibition of bipolar cells may manifest different kinetics that combine with amacrine cell presynaptic release, such that GABA A R-and glyR-mediated inhibition predominantly control the magnitude of bipolar cell glutamate release, whereas GABA Cmediated inhibition controls the timing of bipolar cell glutamate release by increasing its transiency (Eggers and Lukasiewicz, 2011;Eggers and Lukasiewicz, 2006a;2006b;2010;Eggers et al, 2007). Crossover inhibition networks may appropriate these kinetic differences to increase the range and complexity of bipolar cell and ganglion cell responses.…”

Glycine receptor subunits -a2 and a3 participate in different inhibitory circuits that alter the receptive field organization of on- and off-center retinal ganglion cells.

“…Inhibitory networks of ACs in the inner retina modulate BC output and shape the magnitude and timing of inhibitory inputs to RGCs, ultimately spatially and temporally tuning their output (Roska et aI, 1998;Eggers and Lukasiewicz, 2006;Eggers et aI, 2007). The contribution of individual AC networks to RGC output is complicated given the diverse morphology ofBCs (10 types) (Ghosh et aI, 2004) and ACs (>20 types) (Masland, 2001).…”