Figure 2.

Activation of presynaptic GABA_C receptors selectively suppresses the initial but not secondary response at short ISIs. A, The excitatory output of retinal BCs to two electrical stimuli separated by variable ISIs was recorded from morphologically identified ON GC. The holding potential (V_h) was −35 mV to examine both NMDAR and AMPAR components. The average PPR, Q2/Q1, was measured at each ISI. Schematics on the left illustrate the retinal circuitry and stimulation paradigm used to elicit and record electrically evoked responses in GCs in a retinal slice. Inputs to BCs were directly activated by a brief electrical pulse (top electrode). Evoked EPSCs were recorded from the corresponding ON GC (bottom electrode). Representative eEPSCs evoked by pairs of stimuli with variable ISIs recorded in control conditions and in the absence of GABA_C-mediated presynaptic inhibition (+TPMPA, 50 μm). The arrowheads denote the time of the first (filled) and the second (open) electrical pulses. The stimulus artifacts at response onset were removed for clarity. When presynaptic inhibition is present, depression in the second response of the pair is reduced. B, C, Superimposed responses in the presence and absence of presynaptic inhibition for total (mostly NMDAR) (B) and isolated AMPAR-mediated (C) current at a 100 ms ISI. D, E, Paired-pulse plasticity profiles (Q2/Q1, as a function of ISI) in the presence and absence of presynaptic inhibition for total (n = 10) (D) and AMPAR (n = 5) (E) eEPSCs. Evoked EPSCs were isolated using a cocktail of inhibitory blockers (100 μm bicuculline, 5 μm strychnine). Statistical comparisons were made using paired t tests with significance at p < 0.05.