Behavioral and sleep/wake characteristics of mice lacking norepinephrine and hypocretin

Hunsley, Melissa; Curtis, Wendy; Palmiter, Richard D.

doi:10.1111/j.1601-183x.2005.00179.x

Cited by 16 publications

(15 citation statements)

References 43 publications

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“…Correlations were derived from data from all rats (n ϭ 23) in Table 1 2005). Deletions of both HCRT and DBH in mice (combined knock-out) also does not lead to more fragmented sleep versus single gene deletions (Hunsley et al, 2006). In the present study, the lesioned rats had fewer short (Ͻ1 min) bouts of wake, non-REM and REM sleep, and more long bouts (5-10 min long) of non-REM sleep.…”

Section: Discussionmentioning

confidence: 56%

“…This is the case in neurodegenerative diseases including narcolepsy in which all of the underlying HCRT neurons need not be destroyed for a sleep abnormality to be clearly evident (Thannickal et al, 2000;Gerashchenko et al, 2001). The evidence against the BF, TMN, and LC as conduits of a HCRT-wake-promoting effect also comes from knock-out mice (Parmentier et al, 2002;Hunsley and Palmiter, 2003), including double knock-outs (Hunsley et al, 2006). In the present study, the saporin toxins killed specific neurons.…”

Section: Discussionmentioning

confidence: 70%

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

Blanco-Centurión¹,

Gerashchenko²,

Shiromani³

2007

J. Neurosci.

148

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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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 70%

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

Blanco-Centurión¹,

Gerashchenko²,

Shiromani³

2007

J. Neurosci.

148

112

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“…We reasoned that blockade of a signaling pathway involved in evolutionarily derived sleep loss would have little effect on sleep in surface populations while increasing sleep in cavefish. We tested antagonists directed toward glutamatergic, seretonergic, histaminergic, cholinergic, dopaminergic, and noradrenergic systems that have previously been implicated in sleep [Cirelli, 2009;Hunsley et al, 2006;Parmentier et al, 2002;Pollock and Mistlberger, 2003;Simon et al, 2011;Stone et al, 1992;Wisor et al, 2003] ( fig. 1 a).…”

Section: Resultsmentioning

confidence: 99%

“…Elevated serotonin signaling in mice selectively increases REM sleep, suggesting a sleep-promoting role for serotonin [Wisor et al, 2003]. Conversely, mice lacking norepinephrine and epinephrine have an increase in total sleep and a decrease in sleep latency, and mice lacking histamine show an increase in sleep, indicating these neurotransmitters are wake promoting systems [Hunsley et al, 2006;Parmentier et al, 2002]. The amino acid neurotransmitters GABA and glutamate have also been implicated in the regulation of sleep.…”

Section: Introductionmentioning

confidence: 99%

β-Adrenergic Signaling Regulates Evolutionarily Derived Sleep Loss in the Mexican Cavefish

2012

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Sleep is a fundamental behavior exhibited almost universally throughout the animal kingdom. The required amount and circadian timing of sleep differs greatly between species in accordance with habitats and evolutionary history. The Mexican blind cavefish, Astyanax mexicanus, is a model organism for the study of adaptive morphological and behavioral traits. In addition to loss of eyes and pigmentation, cave populations of A. mexicanus exhibit evolutionarily derived sleep loss and increased vibration attraction behavior, presumably to cope with a nutrient-poor environment. Understanding the neural mechanisms of evolutionarily derived sleep loss in this system may reveal critical insights into the regulation of sleep in vertebrates. Here we report that blockade of β-adrenergic receptors with propranolol rescues the decreased-sleep phenotype of cavefish. This effect was not seen with α-adrenergic antagonists. Treatment with selective β1-, β2-, and β3-antagonists revealed that the increased sleep observed with propranolol could partially be explained via the β1-adrenergic system. Morphological analysis of catecholamine circuitry revealed conservation of gross catecholaminergic neuroanatomy between surface and cave morphs. Taken together, these findings suggest that evolutionarily derived changes in adrenergic signaling underlie the reduced sleep of cave populations.

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“…For this reason, we limited our discussion of these neurotransmitters. In brief, targeted genetic disruptions of the biogenic amines-specifically, norepinephrine, dopamine, and histamine-have confirmed the wake-promoting actions of these neurotransmitters suggested by lesion and pharmacological approaches (Wisor et al 2001;Vallone et al 2002;Hunsley and Palmiter 2003;Ouyang et al 2004;Popa et al 2005;Waddington et al 2005;Hunsley et al 2006;Monti and Monti 2007;Qu et al 2008). Serotonin, on the other hand, has had a more complicated history, since it may have different effects on REM versus NREM sleep.…”

Section: The Biogenic Aminesmentioning

confidence: 99%

Genetic analysis of sleep

Crocker¹,

Sehgal²

2010

Genes Dev.

141

109

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Almost 20 years ago, the gene underlying fatal familial insomnia was discovered, and first suggested the concept that a single gene can regulate sleep. In the two decades since, there have been many advances in the field of behavioral genetics, but it is only in the past 10 years that the genetic analysis of sleep has emerged as an important discipline. Major findings include the discovery of a single gene underlying the sleep disorder narcolepsy, and identification of loci that make quantitative contributions to sleep characteristics. The sleep field has also expanded its focus from mammalian model organisms to Drosophila, zebrafish, and worms, which is allowing the application of novel genetic approaches. Researchers have undertaken large-scale screens to identify new genes that regulate sleep, and are also probing questions of sleep circuitry and sleep function on a molecular level. As genetic tools continue to be refined in each model organism, the genes that support a specific function in sleep will become more apparent. Thus, while our understanding of sleep still remains rudimentary, rapid progress is expected from these recently initiated studies.

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Behavioral and sleep/wake characteristics of mice lacking norepinephrine and hypocretin

Cited by 16 publications

References 43 publications

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

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

β-Adrenergic Signaling Regulates Evolutionarily Derived Sleep Loss in the Mexican Cavefish

Genetic analysis of sleep

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