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[Preprint]. 2023 Jul 13:2023.07.13.547220. [Version 1] doi: 10.1101/2023.07.13.547220

Figure 1: [Met]5-Enekphalin preferentially inhibited polysynaptic MThal-ACC inhibitory signaling.

Figure 1:

A) Schematic of viral-mediated ChR2 expression in MThal and whole cell voltage clamp recording from layer 5 (L5) ACC pyramidal cells in acute brain slices. B) Representative average optically evoked EPSCs (lower) and IPSCs (upper) recorded under baseline conditions (gray) and in the presence of 0.1 μM ME (blue). C) Concentration response curve generated from EPSC (solid circles) and IPSC (open circles) inhibition as in “B” by various concentrations of ME 25 ms or vehicle. Data are plotted as % inhibition of the peak EPSC or IPSC relative to baseline. Data were fit with a nonlinear fit in Prism. Probability that the two data sets could be fit with the same parameters: p<0.0001. D) Relative inhibition of pairs of EPSCs (solid) and IPSCs (open) by 0.1, 0.3 and 1 μM ME demonstrating that IPSCs were reliably inhibited more than EPSCs. (two-way ANOVA with Šídák’s multiple comparisons test, ****p<0.0001, **p<0.01, *p<0.05). E) change in excitation/ inhibition (E/I balance) caused by vehicle, 0.1, 0.3, and 1 μM ME calculated as (EPSC/IPSC) drug /(EPSC/IPSC)baseline. At 0.1, 0.3 and 1 μM ME the E/I balance increased significantly compared to vehicle (one-way ANOVA with Dunnett’s multiple comparisons, *p<0.05).