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. 2023 Oct 23;10(10):ENEURO.0126-23.2023. doi: 10.1523/ENEURO.0126-23.2023

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Copyright © 2023 Moura et al.

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Figure 2. — Designer receptors exclusively activated by designer drugs (DREADD) activator Gq results in activation and DREADD activator Gi results in inhibition of the hippocampal neuronal circuit. A, pAAV-hSyn-HA-hM3D(Gq)mCherry or pAAV-hSyn-hM4D(Gi)-mCherry virus were injected into the CA1 of the hippocampus at P7. Three weeks later, animals were treated with seven daily intraperitoneal doses of clozapine or saline. Animals were killed 24 h after the last clozapine dose at P35. B, F, Representative expression of hM4D(Gi)mCherry in the hippocampus. D, H, Representative expression of hM3D(Gq)mCherry in the hippocampus. C, Saline treatment in hM4D(Gi)mCherry-expressing mice or (E) saline treatment in hM3D(Gq)mCherry-expressing mice results in no c-fos labeling of Ctip2+ neurons. G, 7-d clozapine treatment in hM4D(Gi)mCherry-expressing mice resulted in low cfos labeling of ctip2+ neurons. H, 7-d clozapine treatment in hM3D(Gq) mCherry-expressing mice resulted in high c-Fos labeling of ctip2+ neurons. I, 7-d clozapine treatment in hM4D(Gi) mCherry-expressing mice resulted in no c-Fos labeling of ctip2+ neurons. J, In vivo array recording of cells in CA1 of the hippocampus of mice injected with intraperitoneal clozapine or saline (vehicle). Top histograms, Representative cells recorded from the hippocampus of littermates infected with hM3D(Gq) and injected with saline (left) or clozapine (right). Middle histograms, Representative cells recorded from the hippocampus of littermates infected with hM4D(Gi) and injected with saline (vehicle; left) or clozapine (right). Bottom histograms, Representative cells recorded from the hippocampus of littermates treated with clozapine but no hM4D(Gi) injection (bottom left) or treated with clozapine but no hM3D(Gq) injection (bottom right). K, Average suppression rates from cells in the hippocampus of N = 3 mice for each condition on the seventh day of clozapine-treated hM3D(Gq), clozapine-treated hM4D(Gi), or saline-treated control mice. Scale bar: 500 μm. Error bars are standard error of the mean. Figure Contributions: Alekhya Parvathaneni and Atehsa Sahagun collected data, Iris Tilton, Alekhya Parvathaneni, and Laura Cocas analyzed data, Laura Cocas and Robert Brock made the figure.