Circuit State
Narcoleptic State
Orexin somata degenerated. TMN & LC receive near-zero orexinergic drive; flip-flop switch unstable.
Wakefulness Drive
0.12
Cataplexy Status
Resisted
Drug & Receptor Kinetics
Lab Notebook: Mechanism
• Orexin-A/B binds OX1R / OX2R (Gq-coupled)
• Downstream: TMN (Histamine), LC (NE), DR (5-HT)
• Synthetic agonist directly rescues downstream GPCR firing in the absence of peptides!