An orexin-sensitive subpopulation of layer 6 neurons regulates cortical excitability and anxiety behaviour.

Fernando Messore; Rajeevan Narayanan Therpurakal; Jean-Philippe Dufour; Anna Hoerder‐Suabedissen; Luiz Guidi; Kim Korrell; Marissa Mueller; Mohammed Abuelem; Armin Lak; David M. Bannerman; Edward O. Mann; Zoltán Molnár

doi:10.1038/s41398-025-03350-2

NeuroscienceTranslational PsychiatryApr 14, 2025

Peer-reviewed journal article

An orexin-sensitive subpopulation of layer 6 neurons regulates cortical excitability and anxiety behaviour.

Fernando Messore iD, Rajeevan Narayanan Therpurakal iD, Jean-Philippe Dufour iD, Anna Hoerder‐Suabedissen iD, Luiz Guidi iD, Kim Korrell, Marissa Mueller iD, Mohammed Abuelem iD, Armin Lak iD, David M. Bannerman iD, Edward O. Mann iD, Zoltán Molnár iD

Abstract

Cortical layer 6 (L6) neurons uniquely respond to orexin - a neuropeptide influencing arousal and emotion. We show that Drd1a-Cre+ neurons in the prefrontal cortex are selectively sensitive to orexin and regulate prefrontal network activation in vitro and in vivo. Chronically silencing these neurons impairs orexin-induced prefrontal activation and reduces anxiety-like behaviour, indicating that orexin-responsive L6 neurons modulate emotional states and may be a substrate for anxiety regulation.

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