Cortical Astrocytes Modulate Emotion Discrimination

Within the “social brain”, the medial prefrontal cortex (mPFC) orchestrates a top-down control over social cognitive processes, particularly the ability to understand others’ emotional states. In this realm, somatostatin-positive (SOM+) inhibitory neurons emerged as a key players in shaping the recognition and response to altered emotions in others. Despite the well-established functional link between cortical inhibitory neurons and astrocytes, the precise contribution of astrocytes to emotion recognition and their potential synergy with inhibitory neurons in social cognition remain elusive. In our study, we employed a comprehensive approach, integrating in vivo chemogenetics, genetics manipulations and calcium imaging with a behavioral task designed to investigate in mice the ability to perceive, process and react to others’ emotions. We first characterized the pivotal role of astrocytes in modulating emotion discrimination abilities. Socio-cognitive deficits resulting from somatostatin optogenetic inhibition were effectively compensated by the activation of astrocytes in the mPFC Moreover, given the recognized influence of the endocannabinoid system on astrocytic activity, we delved into exploring the impact of mPFC astrocytic cannabinoid type-1 (CB1) receptors on social cognition. Our observations suggest that chemogenetic activation of mPFC astrocytes may rescue deficits in emotion discrimination induced by systemic THC administration. Overall, our findings provide novel insights into the significant role played by mPFC astrocytes in the recognition of positive and negative emotional valences, contributing to a more profound understanding of the neurobiology processes underpinning emotion discrimination abilities.