SEX-DEPENDENT CORTICO-AMYGDALAR CIRCUITS CONTROLLING EMOTION RECOGNITION

In social species, the ability to recognize others’ emotional states is essential for appropriate social interactions, yet it often declines with age and is impaired in various neurodevelopmental and neurodegenerative disorders. While emotion recognition has been characterized in both humans and rodents, the underlying neural circuits and how they vary by sex and age remain poorly understood. Here, we used an Emotional state Discrimination Task in TRAP2 transgenic mice to map brain regions engaged during emotion recognition in young and aged animals. Young male and female mice successfully discriminated emotionally altered conspecifics, recruiting the basolateral amygdala (BLA) and medial orbitofrontal cortex (MO) in a sex-dependent manner. Fiber photometry recordings revealed distinct activation dynamics in these regions, and functional disruption of bidirectional BLA-MO projections selectively impaired emotion recognition in male but not female mice. Consistent with these findings, young human participants showed sex-specific engagement of amygdala–prefrontal networks during facial emotion recognition. Moreover, aging selectively impaired emotion recognition in male mice, coinciding with reduced BLA activity. Remarkably, functional activation of the BLA in aged male mice rescued this deficit. Together, these findings highlight a sex-dependent cortico-amygdalar circuit as a conserved neural substrate for emotion recognition and suggest that age-related impairments in socio-cognitive functions may be reversed through targeted circuit-level modulation.