Fig. 6: VTA-DA neurons are over-inhibited in Emx1-Cre;Irsp53fl/fl mice, and optogenetic activation of LH-GABA neurons improves social interaction.
From: The PFC-LH-VTA pathway contributes to social deficits in IRSp53-mutant mice
a–c mIPSC frequency and amplitude in WT and Emx1-Cre;Irsp53fl/fl (cKO) VTA-DA neurons (8–12 weeks). (n = 10 neurons from 3 mice [WT], 10, 3 [cKO], Student’s t test). d–f mEPSC frequency and amplitude in WT and Emx1-Cre;Irsp53fl/fl (cKO) VTA-DA neurons (8–12 weeks). (n = 13, 3 [WT], 11, 3 [cKO], Student’s t test). g Strategy to rescue social behavior of Emx1-Cre;Irsp53fl/fl mice via optogenetic activation of LH-GABA neurons; AAV-mDlx-ChR2-mCherry was injected into the LH and blue light was applied to the VTA while mice engaged in a social behavioral test (12 weeks). h, i Optogenetic activation of LH-GABA neurons improves social approach in Emx1-Cre;Irsp53fl/fl mice in the three-chamber test, as shown by time spent sniffing social and object targets (S, social stranger; O, object) and the preference index (S–O over S + O). Note that there is no genotype x target interaction in the two-way ANOVA for the preference index but the S-O difference is significant on Student’s t test; this is indicative of a moderate rescue. (n = 13 [WT-GFP], 8 [WT-ChR2], 9 [cKO-GFP], 14 [cKO-ChR2], two-way ANOVA, Student’s t test [S-O differences in each group indicated, preference index]). j Optogenetic activation of LH-GABA neurons does not alter the locomotor activity of WT and cKO mice in the three-chamber test, as shown by total distance moved. (n = 13 [WT-GFP], 8 [WT-ChR2], 9 [cKO-GFP], 14 [cKO-ChR2] two-way ANOVA).
