Figure 4. Optogenetic restoration of spiking activity in the presence of AMPA receptor (AMPAR) blockade prevents GABAergic downscaling observed in CNQX alone.

(A) Scatter plots show AMPAR blockade triggers a reduction in miniature inhibitory postsynaptic current (mIPSC) amplitude compared to controls that is prevented when combined with optogenetic stimulation (optostim, control - n=16 from 10 cultures, CNQX - n=8 from 4 cultures, CNQX/optostim - n=13 from 6 cultures). The mean differences are compared to control and displayed in Cumming estimation plots. Significant differences denoted by **p≤0.01, ***p≤0.001. GABAergic mIPSC amplitudes from single neurons (filled circles), where mean values (represented by the gap in the vertical bar) and SD (vertical bars) are plotted on the upper panels. Mean differences between control and treated groups are plotted on the bottom panel, as a bootstrap sampling distribution (mean difference is represented by a filled circles and the 95% CIs are depicted by vertical error bars). (B) Scaling ratio plots show largely multiplicative relationships to control values for both CNQX and CNQX + optostimulation treatments. Cultured neurons for these recordings were obtained from cells plated on multi-electrode arrays (MEAs) (control, CNQX, and CNQX + optostim).