Fig. 5

dCA2 neuronal activity is necessary for the persistence of long-term SRM. A Schematic representation of the experimental design. B Schematic representation of viral injection. Three weeks after stereotaxic injection of AAV₅-hSyn-DIO-hM4D(Gi)-mCherry or AAV₅-hSyn-DIO-mCherry into the dCA2 of Amigo2-Cre mice, mice were subjected to three-chamber paradigm test and long-term SRM retention was tested 7 days after the initial interaction. Mice were intraperitoneally injected with CNO 30 min before the initial interaction. Representative images showing the co-expression of hM4D(Gi)-mCherry and STEP immunoreactivity in dCA2 pyramidal neurons. Scale bar represents 50 μm. C Top, schematic representation of the three-chamber sociability test. Bottom left, time spent by the subject mouse in sniffing directed at the wire cage containing the juvenile stimulus mouse or the empty wire cage. Both hM4D(Gi)/CNO and mCherry/CNO subject mice spent significantly more time interacting with the wire cage containing the juvenile stimulus mouse than the empty wire cage. Bottom right, discrimination index (stimulus minus empty) was similar between groups in the sociability test. D Top, schematic representation of the three-chamber social novelty preference test. Bottom left, time spent by the subject mouse in sniffing directed at the wire cage containing a familiar mouse or a novel 1 mouse, 10 min after the sociability test. Both hM4D(Gi)/CNO and mCherry/CNO subject mice spent significantly more time sniffing the cage containing the novel mouse than the familiar mouse. Bottom right, discrimination index (novel 1 minus familiar) was comparable between groups in the social novelty preference test. E Top, schematic representation of the three-chamber long-term SRM test. Bottom, time spent by the subject mouse in sniffing directed at the wire cage containing a familiar mouse or a novel 2 mouse, 7 days after the initial interaction. mCherry/CNO, but not hM4D(Gi)/CNO, subject mice spent significantly more time sniffing the cage containing the novel mouse than the familiar mouse. Bottom right, discrimination index (novel 2 minus familiar) of hM4D(Gi)/CNO subject mice was significantly less than mCherry/CNO subject mice in 7-day long-term SRM test. The total number of animal examined is indicated by n in parenthesis. Error bars represent the SEM; **P < 0.01, ***P < 0.001