OPIOID-MEDIATED SUPPRESSION OF INHIBITION DURING LEARNING AND MEMORY

Opioid receptors within the central nervous system regulate pain sensation and mood and are key targets for drugs of abuse. Within the hippocampus, mu-opioid receptors (MORs) are enriched in inhibitory parvalbumin-expressing interneurons (PV-INs), with MOR agonists suppressing PV-IN activity. PV-INs critically regulate hippocampal activity important for learning and memory, yet it is unknown how opioid-mediated neuromodulation of PV-INs alters thus dynamic. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in acute hippocampal slices from mice, nonhuman primates, and humans. This hippocampal disinhibitory motif was established in early development, when immature PV-INs and opioids were found to regulate early population activity. In adulthood, acute opioid-mediated modulation was partially occluded with morphine pretreatment, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Ongoing in vivo 2-photon calcium imaging experiments are exploring a functional role for opioids in altering microcircuit function and spatial learning and memory. Together, these findings demonstrate that opioids exert a targeted modulatory effect on hippocampal PV-INs that is established in early development and conserved across evolution.