HTR6 is required for DR-induced LTP.

LTP of fEPSPs induced by TS was recorded at Schaffer collateral-CA1 synapses of hippocampal slices. Time course of LTP (A, D, G, N), representative traces of average fEPSPs recorded at the baseline (B, E, H, O; black) and during the last 10 minutes of LTP (all other colors), and the average LTP magnitude (C, F, I, P) in various groups. (A–C) Hippocampal slices isolated from WT mice fed on AL or DR diet for 8 weeks were treated with bath application of saline (blue and red), 20 μM WAY (orange), and/or 30 μM SB (WAY + SB, green) 10 minutes prior to TS (horizontal line). (D–F) Hippocampal slices isolated from WT mice receiving 6 weeks of vehicle (“Veh,” blue) or corticosterone (“Cort,” red) treatment in the drinking water. (G–I) Hippocampal slices isolated from HTR6 KO mice fed on AL (blue) or DR (red) diets for 8 weeks. (N–P) Hippocampal slices isolated from HTR6 KO mice transfected with pCMV–GFP (blue) or pCMV–HTR6–GFP (red) plasmid. Data are presented as mean ± SEM (n = 6–9 slices in each group). *P P t test or one-way ANOVA with Fisher’s LSD post hoc test. (J–K) Representative micrographs showing that pCMV–HTR6–GFP plasmid was transfected into the hippocampal CA1 region of HTR6 KO mice; GFP signal was detected under a fluorescent microscope (blue: DAPI [J], green: GFP [K], merged image [L]). (M) HTR6 mRNA expression levels of hippocampal tissues from HTR6 KO mice transfected with pCMV–GFP or pCMV–HTR6–GFP plasmid. Data are presented as mean ± SEM (n = 6 in each group). ***P t test. Underlying data can be found in S1 Data. AL, ad libitum; DG, dentate gyrus; DR, dietary restriction; fEPSP, field excitatory postsynaptic potential; GFP, green fluorescent protein; HTR6, 5-hydroxytryptamine receptor 6; KO, knockout; LSD, least significant difference; SB, SB 399885 hydrochloride; TS, tetanic stimulation; WAY, WAY 208466 dihydrochloride; WT, wild type.