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The Journal of Neuroscience, September 15, 2002, 22(18):7835-7839
BRIEF COMMUNICATION
Selective Action of Orexin (Hypocretin) on Nonspecific Thalamocortical Projection NeuronsLaurence Bayer1, *, Emmanuel Eggermann1, *, Benoît Saint-Mleux1, Danièle Machard1, Barbara E. Jones2, Michel Mühlethaler1, and Mauro Serafin1 1 Département de Physiologie, Centre Médical Universitaire, 1211 Geneva 4, Switzerland, and 2 Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4
As is evident from the pathological consequences of its absence in narcolepsy, orexin (hypocretin) appears to be critical for the maintenance of wakefulness. Via diffuse projections through the brain, orexin-containing neurons in the hypothalamus may act on a number of wake-promoting systems. Among these are the intralaminar and midline thalamic nuclei, which project in turn in a widespread manner to the cerebral cortex within the nonspecific thalamocortical projection system. Testing the effect of orexin in rat brain slices, in two nuclei of this system, centromedial (CM) nuclei and rhomboid nuclei, we found that it depolarized and excited all neurons tested through a direct postsynaptic action. An additional analysis of this effect in CM neurons indicates that it results from the decrease of a potassium conductance. By a detailed comparison of the effects of orexin A and B, we established that orexin B was more potent than orexin A, indicating the probable mediation by orexin type 2 receptors. In contrast to its effect on the nonspecific thalamocortical projection neurons, orexin had no effect on the specific sensory relay neurons of the somatic, ventral posterolateral, and visual dorsal lateral geniculate nuclei. Orexin differs in this regard from norepinephrine and acetylcholine, to which neurons in the specific and nonspecific systems are sensitive. Orexin may thus act in the thalamus to promote wakefulness by exciting neurons of the nonspecific thalamocortical projection system, which, through widespread projections to the cerebral cortex, stimulate and maintain cortical activation.
Key words: arousal; intralaminar nuclei; midline nuclei; rat; sleep; wakefulness
* L.B. and E.E. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22187835-05$05.00/0
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