Figure 6
Elimination of AMPAR subunits diminishes the role of CGE interneurons in both feedforward and feedback inhibition onto CA1 pyramidal neurons. (A) Upper: Schematic of canonical feedforward inhibitory circuit within the CA1 circuit together with electrode placement. Lower: Evoked monosynaptic EPSCs (inward current) and disynaptic IPSCs (outward current) recorded at Vhold = −30 mV from CA1 pyramidal cells in WT (black traces), and CGE GluA1-3 KO (blue traces). Dashed traces show complete elimination of both mono- and disynaptic evoked events by DNQX and APV. (B) Schematic of canonical feedback inhibitory circuit onto CA1 pyramidal cell together with stimulating and recording electrode placement. Lower traces show evoked disynaptic IPSCs recorded at Vhold = −70 mV from CA1 pyramidal cells in WT, and CGE GluA1-3 KO under control and in the presence of the CB1 receptor agonist WIN55, 212-2. Dashed traces show residual events recorded in the presence of DNQX and APV confirming the disynaptic nature of evoked inhibition. (C) Group data for feedforward inhibition (left) feedback inhibition (middle) and the degree of WIN sensitivity of feedback inhibition in both WT and GluA1-3 KO. Significance of the differences between groups compared was calculated with Wilcoxon-Mann-Whitney Test. For Feedforward Inhibition (IPSC/EPSC): WT, n = 5 and GluA1-3 KO, n = 7; p = 0.01. For Feedback Inhibition (Normalized PSC): WT, n = 12 and GluA1-3 KO, n = 9; p = 0.034 and WIN Sensitivity (WIN/baseline PSC): WT, n = 20 and GluA1-3 KO, n = 13; p = 0.011. *p < 0.05.
