Fig. 3: DREADD manipulation of CeA–CRF neurons during fear extinction.

a Schematic of bilateral injection of AAV1-FLEX-hM4Di-YFP into the CeA of CRF-Cre mice (inset: immunohistochemistry for hM4Di-YFP expression pseudo-colored yellow, scale bar: 250 μm). Ef1α elongation factor 1 alpha promoter. Control mice were injected with AAV1-FLEX-YFP. b CNO (1 mg/kg) was injected (n = 10/group) immediately following acquisition training (5 CS-US pairings) followed 30 min later by extinction training 30 CS-only presentations. The next day (24 h), 4 CS-alone trials were given to test the recall of extinction memory. Acquisition (left) and extinction (middle) are not altered by CeA–CRF neuronal inhibition during extinction training, but fear extinction recall (right) is significantly enhanced (Unpaired Student’s t-test, *P < 0.05). c Bilateral injection of AAV1-FLEX-hM3Dq-YFP into the CeA of CRF-Cre mice (inset: immunohistochemistry for hM3Dq-mCherry expression pseudo-colored red, scale bar: 250 μm). Control mice were injected with AAV1-FLEX-mCherry. d CNO (1 mg/kg) was injected (n = 10/group) 30 min prior to delay extinction training (24 h after acquisition). Acquisition (left) and extinction (middle) are not altered by enhancing CeA–CRF neuronal activity during delay extinction training, but fear extinction recall (right) is significantly impaired (Unpaired Student’s t-test, *P < 0.05). Data are presented as mean ± S.E.M.