Mu and delta opioid receptors modulate inhibition within the prefrontal cortex through dissociable cellular and molecular mechanisms

The endogenous opioid system regulates behaviors that rely on prefrontal cortex (PFC) function. Previous studies have described opioid receptor expression within cortical GABAergic interneurons, but a detailed understanding of how Mu, Delta, and Kappa opioids regulate different interneuron subtypes and cortical microcircuits has not been reported. We use whole-cell patch-clamp electrophysiology, genetically engineered mice, and optogenetics to assess MOR, DOR, and KOR regulation of PFC inhibitory transmission, demonstrating that MOR and DOR inhibition of interneurons display qualitative and quantitative variation across GABAergic circuits within mouse prelimbic PFC.