Figure 5. Acute pharmacological inhibition of OXTR leads to impaired social interaction preference and altered neuronal response profile in the MeA.

(A–C) Comparison of times spent in each interaction zone (t test), social preference scores (paired t test) and distance traveled (paired t test) of the subjects (Oxtr^flox/flox) before and after IP injection of OXTR antagonist (OXTR-A). ***p<0.001, **p<0.01. (D) Structure of combined pharmacology and electrophysiology experiments. Sensory responses were determined prior to drug application (~50 min), followed by a 10 min baseline period. Drugs were injected IP, and a second baseline period was collected. Finally, sensory responses were determined after drug application. (E) Firing rate (spikes/second) for single units in the absence of sensory stimuli (abscissa: firing rate before antagonist; ordinate: firing rate after antagonist; log scale). (F) Responses of a single MeA unit to sensory stimuli before and after the mouse was injected with OXTR-A. For each panel, raster plots indicating the timing of individual action potentials elicited by multiple presentations of the same stimulus (shaded region). Histograms of the mean response and standard error for the same data are shown below each raster plot. Time zero indicates alignment to the start of stimulus presentation. (G) Comparison of responses to male, female, and predator stimuli before and after antagonist injection. Grey bars: percentage of single MeA units that responded to each stimulus (nonparametric ANOVA; p<=0.05). Colored bars: percentage of single units that responded most strongly for the indicated stimulus. Asterisks indicate a significant difference in the fraction of responsive units before and after OXTR-A injection (permutation t-test; *p<0.05; **p<0.001) (H) Comparison of response strength before and after OXTR-A injection for all single units responding to a given stimulus. Grey points indicate single units with a statistically significant response to the stimulus plotted in each axis. Colored points indicate units with a significant response that was also the strongest response (compared with responses to the other stimuli). Abscissa: (post-pre)/(post + pre) prior to OXTR-A injection. Ordinate: (post-pre) / (post + pre) after OTRA injection. (I–J) Selectivity of MeA units to sensory stimuli before (I) and after (J) OXTR-A injection. Each point represents the sensory responses of an individual unit with at least one significant response to male, female, or predator stimuli.

Figure 5—figure supplement 1. Mapping of OXT outputs from the PVN and the SON.

(A) Summarized distribution and density of OXT fibers derived from the PVN or SON in different brain areas. OXT fibers are mapped by injecting a Cre-dependent AAV-ChR2-YFP to either the PVN or the SON of Oxt-iCre mice, and fine fibers are revealed by GFP immunostaining. For each nucleus, two virgin female and two virgin male mice were analyzed. Four equal series of 50 μm thick coronal sections were prepared and one brain series from each mouse was analyzed for the number of fibers per mm². (B) OXT fibers derived from the OXT-expressing neurons in the PVN (Left) and SON (Schultz et al., 2000) in selected brain areas. Scale bar = 100 um.