Neurobiology of Hypocretin and Hypocretin-Induced Arousal.
The hypocretins (orexins) are a recently-identified peptide family. Dysregulation of hypocretin neurotransmission appears to play a critical role in the arousal disorder, narcolepsy. Hypocretins are synthesized solely within a small population of neurons located within the lateral hypothalamus which send a widespread efferent projection throughout the CNS. Our laboratory is examining the extent to which hypocretins are necessary for alert waking and the neural circuitry underlying hypocretin-induced alterations in behavioral state. As part of this, we are interested in the extent to which these peptides might participate in stress. Questions of interest include: 1) where in the brain do hypocretins act to modulate behavioral state;		2) to what extent do hypocretins alter noradrenergic and dopaminergic neuronal activity; 3) how are hypocretins neurons organized anatomically? and 4) to what extent do hypocretin-producing and hypocretin-responsive neurons display state-dependent alterations in activity. When completed, these studies will provide critical information regarding the neurobiology of behavioral state and state-dependent processes. Additionally, these studies may provide insight into the neural mechanisms underlying the arousal disorder, narcolepsy, and facilitate development of novel pharmacological treatments for this disorder.
Related Publications: España, RA. (2001) Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action. Neuroscience, 106(4), 699-715. España RA, Plahn S, and Berridge CW. (2002) Circadian-Dependent and Circadian-Independent Behavioral Actions of Hypocretin/Orexin. Brain Research, 943: 224-236. España, RA, Valentino, RJ, Berridge, CW. (2003) Fos immunoreactivity in hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons: effects of diurnal and nocturnal spontaneous waking, stress and hypocretin-1 administration. Neuroscience, 121(1): 201-217. España, RA, Reis, KM, Valentino, RJ, Berridge, CW. (2005) Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal-related structures. J Comp Neurol, 481(2):160-78. Vittoz, NM, Berridge, CW. (2005) Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area. Neuropsychopharmacology, in press. back to list of Current Research projects

Department of Psychology
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University of Wisconsin at Madison
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© 2001 by the Board of Regents of the University of Wisconsin System.
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