Fig. 11.

Contribution of NMDA receptors to OFF and ON parasol cells contrast sensitivity. (A and B) Effect of D-AP5 (50 µM), a selective NMDA receptor antagonist, on spike discharge in response to variation in stimulus contrast (1-mm field diameter) for OFF (A) and ON (B) parasol cells. Plots show spike response amplitude as a function of contrast for control (solid circles), D-AP5 application (open circles) and wash of D-AP5 (gray circles). Solid lines are Naka–Rushton fits (OFF control s_e = 0.8, D-AP5 s_e = 0.5, and wash s_e = 1.8; ON control s_e = 2.1, D-AP5 s_e = 1.9, and wash s_e = 3.8). Contrast gain values were not significantly altered by D-AP5 in OFF (control 3.6 ± 1.0, D-AP5 4.7 ± 1.1, and wash 3.1 ± 0.4) or ON cells (control 2.8 ± 0.5, D-AP5 2.1 ± 0.4, and wash 3.1 ± 0.4). Inset plots to the right of (A and B) show fractional change in spike rate relative to control values; OFF cells showed a smaller reduction in spike rate than ON cells and also showed a paradoxical increase in spike rate relative to control at the lowest stimulus contrasts. (C and D) Resolution of AMPA/Ka and NMDA conductances at 6, 12, 25, and 50% stimulus contrast during the block of synaptic inhibition (GABA_A, GABA_C, and glycine receptor block as described in Fig. 5 and 6) for OFF (B) and ON (F) parasol cells. Families of light-evoked post-synaptic currents shown on the left; derived AMPA/Ka, NMDA and inhibitory conductances shown on the right using the model described in Fig. 10 (see also Materials and methods); I–V plots for the 50% responses shown below current traces. (E and F) Plots of peak G_AMPA/Ka and G_NMDA-55 calculated from control data (circles) and data collected after the block of synaptic inhibition (diamonds) as a function of contrast for OFF (C) and ON (G) parasol cells. Solid lines are Naka–Rushton fits (OFF cells: control AMPA s_e = 1.4 and NMDA s_e = 1.4, and inhibitory block AMPA s_e = 2.0 and NMDA s_e< 0.3; ON cells: control AMPA s_e = 1.1 and NMDA s_e = 0.2 and inhibitory block AMPA s_e = 2.2 and NMDA s_e = 0.2). G_AMPA/Ka shows steep contrast gain and saturation (OFF cells: contrast gain was 1.6 ± 0.9 for control and 1.3 ± 0.7 with inhibition blocked; ON cells: contrast gain was 0.7 ± 0.1 for control and 1.2 ± 0.2 with inhibition blocked). G_NMDA-55 shows a shallow contrast gain without saturation (OFF cells: contrast gain was 0.5 ± 0.2 for control and 0.2 ± 0.0 with inhibition blocked; ON cells: contrast gain was 0.2 ± 0.0 for control and 0.3 ± 0.1 with inhibition blocked). The block of synaptic inhibition increases G_AMPA/Ka conductance but has no significant effect on the G_NMDA. (G and H) Plot of percentage G_NMDA-55 [peak NMDA conductance/(peak total excitatory conductance + peak NMDA conductance)] as a function of contrast for OFF (G) and ON (H) cells calculated from control data (circles) and data collected after the block of inhibition (diamonds). The dotted line indicates the average. As stimulus contrast decreases, the NMDA contribution increases.