Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2–saporin on sleep in Long–Evans rats

Gerashchenko, Dmitry; Blanco-Centurión, Carlos; Greco, Mary Ann; Shiromani, Priyattam J.

doi:10.1016/s0306-4522(02)00575-4

Cited by 112 publications

(84 citation statements)

References 36 publications

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“…Some loss of orexinergic neurones was evident in the perifornical region in some rats; however, this was not statistically significant in the group as a whole. The destruction of orexinergic neurones by local injection of OxSap into the LHA is consistent with previous reports (Gerashchenko et al, 2001(Gerashchenko et al, , 2003Blanco-Centurion et al, 2007;Furlong and Carrive, 2007;Frederick-Duus et al, 2007;Vetrivelan et al, 2009;Anaclet et al, 2010;Di Sebasiano et al, 2010.…”

Section: Discussionsupporting

confidence: 92%

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

et al. 2011

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(2012) Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule. Journal of Psychopharmacology, 26 (6 A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.

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Section: Discussionsupporting

confidence: 92%

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

et al. 2011

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“…5, available at www.jneurosci.org as supplemental material). In our previous studies (Gerashchenko et al, 2001a(Gerashchenko et al, , 2003Zhang et al, 2007), such episodes were easily identified.…”

Section: Effects On Sleep-wakementioning

confidence: 90%

“…Consistent with such a neuronal degeneration, narcoleptic patients have reduced CSF levels of HCRT . Mice (Chemelli et al, 1999;Hara et al, 2001) and rats (Gerashchenko et al, 2001a(Gerashchenko et al, , 2003Beuckmann et al, 2004) with either loss of HCRT or of the HCRT neurons exhibit symptoms of narcolepsy. Canines with narcolepsy possess a mutation in the hypocretin-2 receptor (Lin et al, 1999) and mice with a deletion of this receptor (Willie et al, 2003) also show symptoms of narcolepsy.…”

Section: Introductionmentioning

confidence: 99%

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

Blanco-Centurión¹,

Gerashchenko²,

Shiromani³

2007

J. Neurosci.

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150

112

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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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“…However, to put this finding into perspective, this change is much larger than changes in sleep that are seen after the lesions of the LC (Jones et al, 1977), the LDT (Webster and Jones, 1988), the DRN (Mouret and Coindet, 1980), the orexinergic cells (Hara et al, 2001), the basal forebrain cholinergic cells (Wenk et al, 1994), or the histaminergic tuberomammillary nucleus (Gerashchenko et al, 2004). Only large lesions of the lateral hypothalamic area (combining loss of orexinergic and other unidentified neurons) have been found to cause such substantial changes in wakefulness (Gerashchenko et al, 2001(Gerashchenko et al, , 2003. Hence, it is likely that the vPAG dopaminergic neurons make a major contribution to maintaining wakefulness.…”

Section: Technical Considerationmentioning

confidence: 99%

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

Lü

Jhou²,

Saper³

2006

J. Neurosci.

415

309

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Recent evidence suggests that dopamine plays an important role in arousal, but the location of the dopaminergic neurons that may regulate arousal remains unclear. It is sometimes assumed that the dopaminergic neurons in the ventral tegmental area that project to the prefrontal cortex and striatum may regulate the state of arousal; however, the firing of these dopaminergic neurons does not correlate with overall levels of behavioral wakefulness. We identified wake-active dopaminergic neurons by combining immunohistochemical staining for Fos and tyrosine hydroxylase (TH) in awake and sleeping rats. Approximately 50% of the TH-immunoreactive (TH-ir) cells in the ventral periaqueductal gray matter (vPAG) expressed Fos protein during natural wakefulness or wakefulness induced by environmental stimulation, but none expressed Fos during sleep. Fos immunoreactivity was not seen in the substantia nigra TH-immunoreactive cells in either condition. Injections of 6-hydroxydopamine into the vPAG, which killed 55-65% of wake-active TH-ir cells but did not injure nearby serotoninergic cells, increased total daily sleep by ϳ20%. By combining retrograde and anterograde tracing, we showed that these wake-active dopaminergic cells have extensive reciprocal connections with the sleep-wake regulatory system. The vPAG dopaminergic cells may provide the long-sought ascending dopaminergic waking influence. In addition, their close relationship with the dorsal raphe nucleus will require reassessment of previous studies of the role of the dorsal raphe nucleus in sleep, because many of those experiments may have been confounded by the then-unrecognized presence of intermingled wake-active dopaminergic neurons.

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Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2–saporin on sleep in Long–Evans rats

Cited by 112 publications

References 36 publications

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

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

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

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