Our research focuses on the regulation of sleep and wakefulness, with an emphasis on understanding the neurobiology of narcolepsy. Orexin (hypocretin)-containing neurons of the hypothalamus promote wakefulness, and individuals with narcolepsy have a loss of these cells resulting in excessive daytime sleepiness. One of our long-term goals is to identify the mechanisms regulating the activity of orexin neurons. We have found that these neurons are active during wakefulness, and we are now determining the neural and humoral factors that control this activity. Using innovative neural tracing techniques, we are identifying the projections to the orexin neurons, and we are studying the behavior of orexin knockout mice to determine whether orexin influences the circadian timing of sleep/wake behavior. To determine which brain regions mediate the wake-promoting effects of orexin, we have produced mice in which we can knock out or knock in orexin receptors within specific brain regions. Clinical studies include neuropathologic studies of the brains of people with narcolepsy, measurement of sleep-related changes in orexin concentration, and studies of metabolism and glucose regulation in narcolepsy.
Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, and Scammell TE. Behavioral State Instability in Orexin Knock-Out Mice. Journal of Neuroscience 2004, 24:6291-6300.
Crocker, A, Espaņa, RA, Papadopoulou, M, Saper, CB, Faraco, J, Sakurai, T, Honda, M, Mignot, E, and Scammell, TE. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology. 2005, 65:1184-8.
Yoshida K, McCormack S, Espana RA, Crocker A, and Scammell TE. Afferents to the orexin neurons of the rat brain. J Comp Neurol. 2006 494:845-861.
Diniz Behn, C, Kopell, N, Brown, EN, Mochizuki, T, Scammell, TE. Delayed orexin signaling consolidates wake and sleep: physiology and modeling. J Neurophysiol, 2008 99:3090-103.
External Recognition:
Member NIH BRS study section 2007-2011
Member of the Board of Directors, Sleep Research Society, 2007-2010
Weitzman Award 2006
Grand Rounds: Yale University, 10/07;University of Toronto, 9/07; Brown University, 2/06; Boston Univ. 3/06; Univ. Penn 3/06; BIDMC 10/04, Univ. Mass 10/04
Invited lectures: University of Zurich, 3/08; WorldSleep07, Cairns Australia, 9/07; Netherlands Institute for Neuroscience, 2/08;Leiden University Medical Center, Netherlands, 1/08
Major Collaborative Activities:
Collaboration with Brad Lowell to produce mice with inducible expression of orexin receptors.
Collaborations with Beth Klerman and Cecilia Diniz Behn to create mathematical models of sleep/wake behavior
Collaboration with Clif Saper to study hypothalamic mechanisms of sleep/wake regulation.
Collaboration with Alvaro Pascual-Leone to study incidence of substance abuse in narcolepsy
