Effects of Saporin-Induced Lesions of Three Arousal Populations on Daily Levels of Sleep and Wake

The hypocretin (HCRT) neurons are located only in the perifornical area of the lateral hypothalamus and heavily innervate the cholinergic neurons in the basal forebrain (BF), histamine neurons in the tuberomammillary nucleus (TMN), and the noradrenergic locus ceruleus (LC) neurons, three neuronal po...

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Published inThe Journal of neuroscience Vol. 27; no. 51; pp. 14041 - 14048
Main Authors Blanco-Centurion, Carlos, Gerashchenko, Dmitry, Shiromani, Priyattam J
Format Journal Article
LanguageEnglish
Published United States Soc Neuroscience 19.12.2007
Society for Neuroscience
Subjects
Animals
Arousal - drug effects
Arousal - physiology
Intracellular Signaling Peptides and Proteins - physiology
Male
Neurons - drug effects
Neurons - physiology
Neuropeptides - physiology
Orexins
Periodicity
Plant Proteins - toxicity
Rats
Rats, Sprague-Dawley
Ribosome Inactivating Proteins, Type 1 - toxicity
Saporins
Sleep - drug effects
Sleep - physiology
Wakefulness - drug effects
Wakefulness - physiology
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Summary:The hypocretin (HCRT) neurons are located only in the perifornical area of the lateral hypothalamus and heavily innervate the cholinergic neurons in the basal forebrain (BF), histamine neurons in the tuberomammillary nucleus (TMN), and the noradrenergic locus ceruleus (LC) neurons, three neuronal populations that have traditionally been implicated in regulating arousal. Based on the innervation, HCRT neurons may regulate arousal by driving these downstream arousal neurons. Here, we directly test this hypothesis by a simultaneous triple lesion of these neurons using three saporin-conjugated neurotoxins. Three weeks after lesion, the daily levels of wake were not changed in rats with double or triple lesions, although rats with triple lesions were asleep more during the light-to-dark transition period. The double- and triple-lesioned rats also had more stable sleep architecture compared with nonlesioned saline rats. These results suggest that the cholinergic BF, TMN, and LC neurons jointly modulate arousal at a specific circadian time, but they are not essential links in the circuitry responsible for daily levels of wake, as traditionally hypothesized.
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D. Gerashchenko's present address: SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.3217-07.2007