Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development

Caccavano, A. P.; Kimmel, S.; Vlachos, A.; Mahadevan, V.; Kim, J. H.; Vargish, G.; Chittajallu, R.; London, E.; Yuan, X.; Hunt, S.; Eldridge, M. A. G.; Cummins, A. C.; Hines, B. E.; Plotnikova, A.; Mohanty, A.; Averbeck, B. B.; Zaghloul, K.; Dimidschstein, J.; Fishell, G.; Pelkey, K. A.; McBain, C. J.

doi:10.1101/2024.01.20.576455

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bioRxiv · 10.1101/2024.01.20.576455

Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development

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Abstract

Within the adult rodent hippocampus, opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting local micro-circuits. However, it is unknown if this disinhibitory motif is conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in hippocampus proper but not primary neocortex in mice and nonhuman primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif was established in early development when PV-INs and opioids were found to regulate early population activity. 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. Together, these findings demonstrate that PV-INs exhibit a divergence in opioid sensitivity across brain regions that is remarkably conserved across evolution and highlights the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.

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Caccavano, A. P., Kimmel, S., Vlachos, A., Mahadevan, V., Kim, J. H., Vargish, G., Chittajallu, R., London, E., Yuan, X., Hunt, S., Eldridge, M. A. G., Cummins, A. C., Hines, B. E., Plotnikova, A., Mohanty, A., Averbeck, B. B., Zaghloul, K., Dimidschstein, J., Fishell, G., Pelkey, K. A., McBain, C. J.. 2024-01-21. Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development. https://doi.org/10.1101/2024.01.20.576455

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