Social Processing in the Amygdala: Single-Nucleus RNA-Sequencing Reveals Distinct Neuronal Responses to Dominant and Subordinate Cues.

The amygdala serves as a critical neural hub for interpreting social cues, with its distinct subregions and diverse neuronal populations playing specialized roles in processing these signals. Here, we employ single-nucleus RNA sequencing (snRNA-seq) to characterize neuronal responses in the mouse amygdala to olfactory cues associated with social dominance, uncovering distinct activation patterns within glutamatergic and GABAergic populations. We find that a glutamatergic cluster closely aligned with Slc17a7 (VGLUT1) medial amygdala (MeA) neurons preferentially responds to dominant cues. In contrast, a larger glutamatergic Slc17a6 (VGLUT2) cluster associated with MeA, cortical, and basomedial amygdala neurons exhibits a heightened response to subordinate cues, underscoring the MeA’s role in processing social olfactory information. Additionally, a glutamatergic cluster resembling dorsal endopiriform (EPd) neurons responds more strongly to dominant stimuli, supporting the EPd’s role in olfactory perception. We also identify a GABAergic cluster with elevated dopamine receptor 2 (Drd2) expression that predominantly responds to dominant cues, consistent with this receptor’s role in mediating threat responses. Finally, gene co-expression network analysis links cluster-specific gene expression to distinct biological processes. Together, these findings reveal neuronal and molecular mechanisms underlying social processing of dominance-related olfactory signals, enhancing our understanding of the neural substrates of social behavior.