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. Author manuscript; available in PMC: 2022 Jun 14.
Published in final edited form as: Sci Transl Med. 2021 Nov 24;13(621):eabl4580. doi: 10.1126/scitranslmed.abl4580

Fig. 5. Chronically elevated cAMP signaling promotes motivated behavior and spatial memory.

Fig. 5.

(A) Male mice were bilaterally injected with AAV-GFP or AAV-DREADD into the dorsal CA1 and then received 3 weeks of either saline (NS) or CNO before TST (AAV-GFP/NS: 178.2 ± 8.0 s; AAV-GFP/CNO: 167.8 ± 5.8 s; AAV-DREADD/NS: 168.6 ± 10.8 s; AAV-DREADD/CNO: 112.3 ± 7.9 s). An identical setup was used before FST [(B) AAV-GFP/NS: 144.2 ± 7.0 s; AAV-GFP/CNO: 147 ± 5.6 s; AAV-DREADD/NS: 155.5 ± 4.3 s; AAV-DREADD/CNO: 99.2 ± 8.2 s]. (C) Male and female mice were bilaterally injected with AAV-DREADD into dorsal CA1 and then received either NS or CNO in their drinking water for 3 weeks before OLM testing (male AAV-DREADD/NS: 0.21 ± 0.08; male AAV-DREADD/CNO: 0.42 ± 0.07; female AAV-DREADD/NS: 0.08 ± 0.03; female AAV-DREADD/CNO: 0.36 ± 0.05; n = 15, 13, 14, and 14). (D) Number of action potentials fired in each condition as a function of somatic current injection (AAV-GFP/NS: n = 7; AAV-GFP/CNO: n = 11; AAV-DREADD/NS: n = 16; AAV-DREADD/CNO: n = 21; tables S8 and S9). (E) Representative current clamp traces from all four conditions in response to hyperpolarizing 100-pA current injection. The y axis is scaled as in previous figures. (F) Quantification of somatic sag ratio (AAV-GFP/NS: 1.30 ± 0.05; AAV-GFP/CNO: 1.28 ± 0.02; AAV-DREADD/NS: 1.32 ± 0.02; AAV-DREADD/CNO: 1.23 ± 0.02). (G) Representative current clamp traces obtained during stimulation of the TA pathway. Note that colors represent the same conditions as in (A), (D), and (E). (H) Quantification of the proportion of stimuli producing action potentials as a function of TA stimulating electrode intensity (see tables S8 and S9 for statistics). For all panels, *P < 0.05. For (H), #P < 0.05 for effect of drinking water, *P < 0.05 for interaction of drinking water and virus.