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

Abstract 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. This study employs single-nucleus RNA sequencing (snRNA-seq) to characterize the amygdala’s neuronal responses to olfactory cues associated with social dominance, uncovering distinct activation patterns within glutamatergic and GABAergic populations. We find that a glutamatergic cluster, characterized by expression patterns closely aligned with glutamatergic Slc17a7 (VGLUT1) medial amygdala (MeA) neurons, preferentially responds to dominant cues. In contrast, a larger glutamatergic Slc17a6 (VGLUT2) cluster associated with neurons of the MeA, as well as cortical and basomedial amygdala, exhibits a heightened response to subordinate cues, underscoring the MeA region’s role in processing social olfactory information. Additionally, a glutamatergic cluster resembling dorsal endopririform (EPd) neurons responded more to dominant stimuli, supporting the EPd’s role in olfactory perception. We also identified a GABAergic cluster with elevated dopamine receptor 2 ( Drd2 ) expression that predominantly responds to dominant cues, consistent with this receptor’s known role in mediating threat responses. Through gene co-expression network analysis, we linked gene expression within neuronal clusters to specific biological processes. These findings reveal distinct neuronal and molecular mechanisms underlying social processing, particularly in response to dominant and subordinate olfactory signals, thus enhancing our understanding of the neural substrates of social behavior.