Neuron · 2025
Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.
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Caccavano Adam P, Vlachos Anna, McLean Nadiya, Kimmel Sarah, Kim June Hoan, Vargish Geoffrey, Mahadevan Vivek, Hewitt Lauren, Rossi Anthony M, Spineux Ilona, Wu Sherry Jingjing, Furlanis Elisabetta, Dai Min, Leyva Garcia Brenda, Wang Yating, Chittajallu Ramesh, London Edra, Yuan Xiaoqing, Hunt Steven, Abebe Daniel, Eldridge Mark A G, Cummins Alex C, Hines Brendan E, Plotnikova Anya, Mohanty Arya, Averbeck Bruno B, Zaghloul Kareem A, Dimidschstein Jordane, Fishell Gord, Pelkey Kenneth A, McBain Chris J
Аннотация
Within adult rodent hippocampus (HPC), opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), disinhibiting local microcircuits. However, it is unknown whether this disinhibitory motif is conserved across cortical regions, species, or development. We observed that PV-IN-mediated inhibition is robustly suppressed by opioids in HPC proper but not primary neocortex in mice and non-human primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif is established in early development when PV-INs and opioids regulate early population activity. Morphine pretreatment partially occludes this acute opioid-mediated suppression, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Our findings demonstrate that PV-INs exhibit divergent opioid sensitivity across brain regions, which is remarkably conserved over evolution, and highlight the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.