Narcolepsy was first described in the medical literature in the 1870’s, but only in the last 20 years have researchers come to understand its true cause. Narcolepsy type 1 (narcolepsy with cataplexy) is caused by severe loss of the orexin/hypocretin neurons in the hypothalamus, most likely from an autoimmune attack on these cells. Dr. Scammell will review how loss of these specific neurons results in sleepiness and cataplexy, and how this appreciation of the importance of the orexin system is now leading to novel, and hopefully highly effective, therapies for people with narcolepsy.

We focused on studying the functional roles of the adenosine A2A and dopamine D1 Receptors (R) in the basal ganglia and obtained following 4 major findings: (1) Nucleus accumbens (NAc) dopamine D1R-expressing neurons are essential in controlling wakefulness; (2) Opposite to the D1R, A2AR made a prominent contribution to sleep control associated with motivation; (3) The ventral pallidal GABAergic neurons control wakefulness associated with motivation; (4) Striatal adenosine A2AR neurons control active-period sleep, whereas striatal D1R neurons play important roles in controlling wakefulness by integrating the up-stream projections and innervation of down-stream pathways. Taken together, we demonstrated that basal ganglia integrate behaviors with sleep/wakefulness via adenosine and dopamine receptors and discussed the impacts of the BG in insomnia and PD.