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

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.