Fig. 2: AI-PrL pathway hypofunction caused SILA-induced reduction of PrL neuronal activity, leading to altered postpartum social novelty recognition.

A Strategy of in vivo microendoscopic calcium recording of PrL through optogenetic manipulation of the AI-PrL pathway. B Representative image showing Chrimson (red) in the AI-PrL pathway and GCaMP6f (green) underneath a GRIN lens. Scale bars, 1 mm and 100 µm. C Experimental timeline of SIT without and with optogenetic manipulation. D Representative heatmaps of the mouse track during the SN-trials in unstressed dams expressing eNPHR. E Optogenetic inhibition of the AI-PrL pathway decreased social novelty preference (two-way mixed ANOVA, Wilcoxon signed-rank test). N = 8 mice. F Representative heatmaps of the mouse track during the SN-trials in stressed dams expressing Chrimson. G Optogenetic activation of the AI-PrL pathway increased social novelty preference (two-way mixed ANOVA, Wilcoxon signed-rank test). N = 8 mice. H Imaging field of view showing raw calcium fluorescence and regions of interest (ROIs). Scale bar, 100 µm. I Receiver operating characteristic (ROC) curves computed from three example neurons that were categorized as novel-excited [area under ROC curve (auROC) = 0.88], novel-unresponsive (auROC = 0.50), or novel-suppressed (auROC = 0.16). J Representative calcium traces from novel-excited, novel-suppressed, and novel-unresponsive neurons. K, L Representative extracted ROIs and calcium traces from PrL. M PrL activity during interaction with a familiar mouse did not show any differences between stressed and unstressed dams expressing control viruses (Chi-squared test). N Fractions of novel-excited and novel-suppressed cells in stressed dams expressing control viruses were significantly decreased and increased, respectively, compared to unstressed dams expressing control viruses (Chi-squared test). O Optogenetic inhibition of the AI-PrL pathway in unstressed dams decreased and increased the fractions of novel-excited and novel-suppressed neurons in PrL, respectively (Chi-squared test). Optogenetic activation in stressed dams increased and decreased the fractions of novel-excited and novel-suppressed neurons, respectively (Chi-squared test). All data are represented as mean ± SEM. For ANOVAs, * = post hoc Bonferroni, p < 0.05. ** = post hoc Bonferroni, p < 0.01. ns non-significant. See Supplemental Table 3 for details on the statistical analyses.