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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. 4. Hippocampal HCN channels limit motivated behavior and spatial memory.

Fig. 4.

Male and female Hcn2+/+ and Hcn2R/R mice were subjected to TST [(A) male +/+: 179.1 ± 16.3 s; male R/R: 147.0 ± 13.44 s; female +/+: 140.6 ± 29.2 s; female R/R: 67.6 ± 17.5 s] and FST [(B) male +/+: 119.8 ± 7.6 s; male R/R: 30 ± 10.2 s; female +/+: 132.8 ± 16.9 s; female R/R: 37.4 ± 7.6 s, n = 6, 6, 5, and 15]. (C) Male and female Hcn2R/R mice were bilaterally injected with AAV-DREADD and then received intraperitoneal saline or CNO before TST (male R/R saline: 131.7 ± 8.88 s; male R/R CNO: 141.1 ± 6.36 s; female R/R saline: 86.15 ± 13.82 s; female R/R CNO: 100.21 ± 11.36 s, n = 10, 8, 13, and 14). (D) An identical setup was used for FST (male R/R saline: 55.2 ± 8.54 s; male R/R CNO: 51.8 ± 8.65 s; female R/R saline: 40.1 ± 12.9 s; female R/R CNO: 35.4 ± 8.11 s; n = 9, 10, 12, and 12). (E) Hcn2R/R males and females were bilaterally injected in the dorsal CA1 with AAV-DREADD and then subjected to the OLM task. After the training day, mice received either intraperitoneal saline or intraperitoneal CNO (discriminative index: male R/R saline: 0.33 ± 0.10; male R/R CNO: 0.13 ± 0.06; female R/R saline: 0.34 ± 0.13; female R/R CNO: 0.26 ± 0.10; n = 5, 6, 13, and 9). (F) Wild-type male mice were intraperitoneally injected with either saline or citalopram (SSRI) before TST (saline: 126.3 ± 8.23 s; SSRI: 12.8 ± 4.13 s; n = 10 and 10). (G) Wild-type male mice were bilaterally injected with AAV-DREADD and then received SSRI along with either saline or CNO before TST (SSRI/saline: 13.57 ± 6.36 s; SSRI/CNO: 58.66 ± 11.76 s; n = 14 and 18). (H) Wild-type male mice were bilaterally injected with either AAV-GFP or AAV-TRIP8b and then received intraperitoneal citalopram (AAV-GFP/SSRI: 21.57 ± 5.93 s; AAV-TRIP8b/SSRI: 53.00 ± 11.05 s; n = 14 and 15). Please note that between-sex differences are not reported above (see table S6 for statistics). *P < 0.05.