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. 2021 Feb 18;12:1142. doi: 10.1038/s41467-021-21476-x

Fig. 4. Re-expression of histamine H1R in cholinergic neurons in the HDB of BF rescues behavioral deficits manifested in ChAT-Cre;Hrh1fl/fl mice.

Fig. 4

a Representative images of H1R-GFP expression in the HDB of BF in ChAT-Cre;Hrh1fl/fl mice after the microinjection of AAV-CAG-FLEX-Hrh1-GFP (AAV/Hrh1), enlarged images of RNAscope in situ hybridization of Hrh1 and GFP mRNA, and immunostaining of ChAT. The percentage of ChAT+ cholinergic neurons co-expressing GFP, percentage of GFP+ cells co-expressing ChAT, and percentage of GFP+ cells co-expressing Hrh1 mRNA in the HDB were quantified. Left: scale bar, 500 μm. Right: scale bar, 10 μm. n = 5 mice. bh Sensorimotor gating, social behavior, hedonic function, and cognitive behavior in control ChAT-Cre mice injected with AAV-CAG-FLEX-GFP (AAV/GFP), and ChAT-Cre;Hrh1fl/fl mice either injected with AAV/GFP or AAV/Hrh1. b Percentage of prepulse inhibition of the auditory startle reflex across different prepulse intensities. c Time in close interaction and preference index during sociability testing (phase 2) when exposed to a stranger mouse S1. Time in close interaction and preference index during subsequent social novelty recognition testing (phase 3) when exposed to a new stranger mouse S2 together with S1. d The percentage of the weight of cotton left unshredded and nesting score in nest-building test. e Test for sucrose preference as a percentage of all fluid intake within a 48 h period. f Discrimination index in novel object recognition test. g Discrimination index in temporal order memory test. h Percentage of correct choices during choice runs in delayed non-match-to-sample task. i Threshold current to elicit action potential with the increase of injected currents in HDB of BF cholinergic neurons recorded by whole-cell patch-clamp. Spike numbers with the increase of injected currents in BF cholinergic neurons recorded by whole-cell patch-clamp. j Representative traces showing sEPSC (upper) and sIPSC (lower) recorded at −60 mV (upper) and +10 mV (lower) in the same mPFC layer 2/3 pyramidal cell from ChAT-Cre-AAV/GFP (black), ChAT-Cre;Hrh1fl/fl-AAV/GFP (gray), or ChAT-Cre;Hrh1fl/fl-AAV/Hrh1 (green). Quantification of sEPSC and sIPSC charge transfer and sEPSC/sIPSC charge transfer ratios in ChAT-Cre-AAV/GFP, ChAT-Cre;Hrh1fl/fl-AAV/GFP, or ChAT-Cre;Hrh1fl/fl-AAV/Hrh1 mice. All data are presented as mean ± s.e.m. and error bars represent s.e.m. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ns nonsignificant. See also Supplementary Data 2 for further statistical information. Source data are provided as a Source Data file.