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. 2019 Apr 9;116(18):9072–9077. doi: 10.1073/pnas.1820541116

Fig. 4.

Fig. 4.

Targeted chemogenetic activation of GABAergic cells in the ZI can reduce fear generalization. (A) Experimental design: vGAT-CRE animals received intracranial injections of CRE-dependent control or DREADD virus, and after 2 weeks, they were conditioned to high-threat intensities. One day posttraining, CNO was administered i.p. 1 h before testing for fear generalization. BL, baseline; Hab, habituation. (B) vGAT-CRE animals were injected with either the control virus (AAV5-hSyn-DIO-mCherry) or excitatory DREADDs (AAV5-hSyn-DIO-hM3DGq-mCherry) at −1.52 mm posterior to the bregma. (C) Representative image of the GABAergic cells within the ZI infected with mCherry-expressing excitatory DREADDs (in red) and Hoechst-stained nuclei (in blue). (Scale bar: 100 μm.) (D) Animals with expression of DIO-hM3DGq virus in vGAT-CRE–expressing GABAergic cells in the ZI and injected with CNO (DIO-hM3DGq+CNO) 1 h before testing for fear generalization showed a significant decrease in fear response to CS− compared with animals that were infused with the DIO-mCherry virus in vGAT-CRE–expressing GABAergic cells in the ZI and injected with CNO (DIO-mCherry+CNO). (E) Chemogenetic activation of GABAergic cells in the ZI (DIO-hM3DGq+CNO) resulted in a better ability to discriminate between the CS+ and the CS−. **P < 0.05; ****P < 0.0001. Data are represented as mean ± SEM.