Context-invariant socioemotional encoding by prefrontal ensembles

The prefrontal cortex plays a key role in social interactions, anxiety-related avoidance, and flexible context- dependent behaviors, raising the question: how do prefrontal neurons represent socioemotional information across different environments? Are contextual and socioemotional representations segregated or intermixed, and does this cause socioemotional encoding to remap or generalize across environments? To address this, we imaged neuronal activity in the medial prefrontal cortex of mice engaged in social interactions or anxiety-related avoidance within different environments. Neuronal ensembles representing context and social interaction overlapped more than expected while remaining orthogonal. Anxiety-related representations similarly generalized across environments while remaining orthogonal to contextual information. This shows how prefrontal cortex multiplexes parallel information streams using the same neurons, rather than distinct subcircuits, achieving context-invariant encoding despite context-specific reorganization of population-level activity.