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. Author manuscript; available in PMC: 2024 Oct 4.
Published in final edited form as: Neuron. 2023 Jul 21;111(19):3053–3067.e10. doi: 10.1016/j.neuron.2023.06.023

Figure 1: Photoexcitation of mPFC→BLA neurons facilitates fear extinction through BLA eCBs.

Figure 1:

(A-C) Behavioral (A) and in vivo optogenetic (B) procedure for mPFC→BLA photoexcitation during partial (10-trial) extinction training (YFP n=11/ChR2 n=8). Virus expression in mPFC and BLA (C).

(D) Freezing increased over conditioning trials (RM-ANOVA: F(1,13)=63.960, P<0.0001, ηp2=0.73) and decreased over extinction trial-blocks (RM-ANOVA: F(1,17)=56.610, P<0.0001, ηp2=0.34). Lower freezing in opsin groups on early extinction (first 5-trial block) vs extinction retrieval 1 (RM-ANOVA: F(1,17)=5.683, P=0.0291, ηp2=0.17) and on extinction retrieval 2 (RM-ANOVA: F(1,17)=11.170, P=0.0039, ηp2=0.28).

(E,F) Measurement of photoexcitation-related BLA eCB levels (AEA-YFP n=15/AEA-ChR2 n=15, AEA-YFP n=15/AEA-ChR2 n=14) (E). Higher AEA, not 2-AG (P>0.05), levels in ChR2 versus YFP (unpaired t-test: t(28)=2.887, P=0.0074, ηp2=0.23 (F).

(G,H) Systemic SR141716A (SR, CB1R antagonist) prior to combined extinction training/mPFC→BLA photoexcitation (YFP-Vehicle (Veh) n=11/YFP-SR n=9/ChR2-Veh n=9/ChR2-SR n=12) (G). Freezing increased over conditioning trials (RM-ANOVA: F(1,36)=209.800, P<0.0001, ηp2=0.75). Freezing decreased over extinction trial-blocks (RM-ANOVA: F(1,37)=116.700, P<0.0001, ηp2=0.37). Lower freezing in ChR2 versus YFP on extinction retrieval 1 (ANOVA opsin x drug interaction: F(1,37)=4.742, P=0.0359, ηp2=0.10, Holm-Šídák's tests: YFP-Veh versus ChR2-Veh: P=0.0488, all others P>.05) and retrieval 2 (ANOVA opsin x drug interaction: F(1,37)=2.054, P=0.1602, ηp2=0.04, Holm-Šídák's tests: YFP-Veh versus ChR2-Veh: P=0.0023, all others P>.05) (H).

(I,J) Intra-BLA SR141716A prior to combined extinction training/mPFC→BLA photoexcitation (YFP-Veh n=10/YFP-SR n=8/ChR2=Veh n=15/ChR2-SR n=11) (I). Freezing increased over conditioning trials (RM-ANOVA: F(1,40)=306.400, P<0.0001, ηp2=0.77). Freezing decreased over extinction trial-blocks (RM-ANOVA: F(1,40)=76.000, P<0.0001, ηp2=0.28). Lower freezing in ChR2 versus YFP on extinction retrieval 1 (ANOVA opsin x drug interaction: F(1,40)=4.511, P=0.0399, ηp2=0.09, Holm-Šídák's tests: YFP-Veh versus ChR2-Veh: P=0.0029, all others P>.05) and retrieval 2 (ANOVA opsin x drug interaction: F(1,39)=2.323, P=0.1355, ηp2=0.05, Holm-Šídák's tests: YFP-Veh versus ChR2-Veh: P=0.0417, all others P>.05) (J).

Data are represented as mean±SEM. *P<0.05. Table S1 reports full statistical results for all figures.