Insular cortex corticotropin-releasing factor integrates stress signaling with social decision making

Abstract Impairments in social cognition manifest in a variety of psychiatric disorders, making the neurobiological mechanisms underlying social decision making of particular translational importance. The insular cortex is consistently implicated in stress-related social and anxiety disorders, which are associated with diminished ability to make and use inferences about the emotions of others to guide behavior. We investigated how corticotropin releasing factor (CRF), a neuromodulator evoked by both self and social stressors, influenced the insula. In acute slices from male and female rats, CRF depolarized insular pyramidal neurons. In males, but not females, CRF suppressed presynaptic GABAergic inhibition leading to greater excitatory synaptic efficacy in a CRF receptor 1 (CRF 1 ) and cannabinoid receptor 1 (CB 1 ) dependent fashion. In males only, insular CRF increased social investigation, and CRF 1 and CB 1 antagonists interfered with social decision making. To investigate the molecular and cellular basis for the effect of CRF we examined insular CRF 1 and CB 1 mRNAs and found greater total insula CRF 1 mRNA in females but greater CRF 1 and CB 1 mRNA colocalization in male insular cortex glutamatergic neurons which suggest complex, sex-specific organization of CRF and endocannabinoid systems. Together these results reveal a new sex-specific mechanism by which stress and affect contribute to social decision making.