SEX‑SPECIFIC SOCIAL BEHAVIOR AND AMYGDALA CIRCUIT ALTERATIONS IN <EM>POGZ</EM><SUP>+/-</SUP> MICE

Sex‑Specific Social Behavior and Amygdala Circuit Alterations in Pogz^+/- Mice
Autism spectrum disorder (ASD) shows a pronounced male predominance, yet the biological basis for this sex bias remains unclear. POGZ, one of the most significant ASD‑associated genes, is linked to atypical social behavior in humans, and male mice carrying a heterozygous Pogz mutation recapitulate this phenotype. Using this model, we identified robust sex-specific differences in sociability driven specifically by Pogz^+/- males. Across multiple behavioral paradigms, Pogz^+/- males displayed markedly increased social investigation compared to control mice, whereas Pogz^+/- females showed reduced social engagement. In social odor habituation-dishabituation assays, Pogz^+/- males spent significantly more time investigating social odors, consistent with an overly friendly phenotype in humans. C-Fos mapping following social odor exposure revealed increased neuronal activation within amygdala circuits uniquely in Pogz^+/- male mice. To characterize the neurons engaged during social investigation, we applied the TRAP2‑Ai14 activity-dependent labelling system to selectively mark neurons activated during social odor exposure, enabling direct comparison of activated and non‑activated cells through patch‑clamp recordings and single‑nucleus transcriptional profiling (snRNA-seq). Preliminary electrophysiological data reveal distinct intrinsic properties in socially activated neurons, including burst‑like firing and altered spike accommodation. Complementary single-nucleus RNA sequencing indicates Pogz^+/- male-specific changes in the composition of several neuronal populations. Together, these findings reveal pronounced male-biased alterations in amygdala activity and neuronal identity associated with Pogz deficiency, suggesting a strong sex-dependent divergence in the neural processing of social stimuli.