Fig. 4: Restoration of social cognitive deficits through (R)-ketamine-induced activation of the aIC.

a Experimental timeline and schematic of the social memory test using social isolation reared-mice with or without chemogenetic aIC inhibition and representative image of hM4Di-mCherry transduction at the injection site (highlighted in red). b Difference of investigation time to a familiar mouse between 1st trial and indicated trial (2nd to 4th trial) and to a novel mouse (5th trial) in the 1st social memory test 24 h after vehicle and saline treatments. c–e Difference of investigation time to a familiar mouse between 6th trial and indicated trial (2nd to 4th trial) and to a novel mouse (10th trial) in the 2nd social memory test 24 h after vehicle and saline or 20 mg/kg (R)-ketamine treatments (for saline and (R)-ketamine; n = 14 and 16, respectively). Statistical analysis was performed using two-way repeated measured ANOVA, followed by Holm-Sidak multiple comparison test (c): time, F(4, 112) = 7.023, p < 0.0001; treatment, F(1, 28) = 1.57, p = 0.2206; interaction, F(4, 112) = 3.36, p = 0.0123, and using Levene’s test and unpaired t test (d, e). Levene’s test: p = 0.207 (d), p = 0.179 (e); unpaired t test, *p < 0.05. f Immobility time of hM4Di-mCherry-expressing mice in the FST 48 h after drug treatments. Statistical analysis was performed using Levene’s test and unpaired t test (f). Levene’s test: p = 0.707; unpaired t test, *p < 0.05. g Difference of investigation time to a familiar mouse between 1st trial and indicated trial (2nd to 4th trial) and to a novel mouse (5th trial) in the 1st social memory test 24 h after vehicle and saline treatments. h–j Difference of investigation time to a familiar mouse between 6th trial and indicated trial (2nd to 4th trial) and to a novel mouse (10th trial) in the 2nd social memory test 24 h after CNO and saline or 20 mg/kg (R)-ketamine treatments (for saline and (R)-ketamine; n = 15 and 16, respectively). Statistical analysis was performed using two-way repeated measured ANOVA: time, F(4, 116) = 15.03, p < 0.0001; treatment, F(1, 29) = 0.004067, p = 0.9496; interaction, F(4, 116) = 1.352, p = 0.2550, and using Levene’s test and unpaired t test (i, j). Levene’s test: p = 0.276 (i), p = 0.221 (j); unpaired t test, *p < 0.05. k Immobility time of hM4Di-mCherry-expressing mice in the FST 48 h after drug treatments. Statistical analysis was performed using Levene’s test and unpaired t test. Levene’s test: p = 0.441. Black lines, mouse treated with saline in both 1st and 2nd social memory test; Orange line, mouse treated with saline in 1st and (R)-ketamine in 2nd social memory test. Data are presented as the mean ± s.e.m.