Neurotoxic N-methyl-d-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep–wake organization

Lai, Yuan-Yang; Shalita, T.; Hajnik, Tünde; Wu, Juyou; Kuo, Jon‐Son; Chia, Lie‐Gan; Siegel, Jerome M.

doi:10.1016/s0306-4522(98)00429-1

Cited by 48 publications

(34 citation statements)

References 69 publications

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“…The rats with vPAG 6-OHDA lesions did not show the motor hyperactivity seen in animals with VTA lesions (Lai et al, 1999). They also showed a robust daily rhythm of total sleep 3 weeks after the surgery.…”

Section: The Effects Of Dopaminergic Cell Loss In the Pag On Sleep-wamentioning

confidence: 78%

“…Compared with the VTA, vPAG dopaminergic cells have very little input to the ventral striatum but substantial input to the central nucleus of amygdala and the extended amygdala (Hasue and Shammah-Lagnado, 2002), whereas the VTA and SN do not project to the VLPO, which is a major target of the vPAG (Chou et al, 2002). Neurotoxic lesions of the VTA that spare the vPAG region cause a decrease rather than an increase in sleep in rats (Lai et al, 1999) and produce motor hyperactivity (Galey et al, 1977;Koob et al, 1981). However, 6-OHDA lesions that include both the VTA and the vPAG regions were found to produce a 20% increase in total sleep (Sakata et al, 2002), which is similar to our lesions of the vPAG alone.…”

Section: Technical Considerationmentioning

confidence: 99%

“…VTA neurons that project to the prefrontal cortex and striatum (Steinfels et al, 1983;Freeman et al, 2001) are often assumed to play this role; however, the firing of VTA neurons or SN neurons that project to the striatum does not correlate with overall levels of behavioral wakefulness in rats (Miller et al, 1983). Furthermore, neurotoxic lesions of the VTA do not decrease behavioral wakefulness (Lai et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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

Lü

Jhou²,

Saper³

2006

J. Neurosci.

412

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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Section: The Effects Of Dopaminergic Cell Loss In the Pag On Sleep-wamentioning

confidence: 78%

Section: Technical Considerationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lü

Jhou²,

Saper³

2006

J. Neurosci.

412

309

View full text Add to dashboard Cite

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“…In contrast, the role assigned to DA in sleep-wake regulation has been relatively limited, because the activity of DA neurons in the ventral tegmental area and substantia nigra pars compacta is not significantly modulated by the sleep-wake cycle (Miller et al, 1983); and, furthermore, neurotoxic lesions of the ventral tegmental area do not decrease behavioral wakefulness (Lai et al, 1999). However, the results of in vivo microdialysis studies indicate that during the light period, when rats typically sleep, extracellular DA levels are lower than during the dark period in the medial prefrontal cortex and the nucleus accumbens (Léna et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Essential Role of Dopamine D₂Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice

Qu¹,

Xu²,

Yan³

et al. 2010

J. Neurosci.

176

122

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Dopamine (DA) and its D 2 receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep-wake regulation remain unclear. Herein we investigated the role of D 2 R in sleep-wake regulation by using D 2 R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D 2 R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75-2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D 2 R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D 2 R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D 2 R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D 2 R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.

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“…15 Many subcortical structures, such as the basal forebrain, dorsal and central superior raphe nuclei, and the reticular formation of the pons and medulla, also seem to be involved in the initiation of sleep and the oscillation between REM and non-REM states. [16][17][18][19][20][21][22] Current thinking maintains that there is a dynamic interplay between the circadian pacemaker in the SCN modulating arousal (process C) and flexible homeostatic influences modulating sleep tendency (process S) possibly based in these other subcortical structures. 12,23 All of these structures potentially could be damaged as a consequence of Alzheimer disease (AD) 16 and frontotemporal degenerative dementias (FTD), 24 and their deterioration could explain many sleep architecture and continuity changes seen in these illnesses.…”

mentioning

confidence: 99%

Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease and Frontotemporal Degeneration

Harper¹,

Stopa²,

McKee³

et al. 2001

Arch Gen Psychiatry

216

111

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Background: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia.

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Neurotoxic N-methyl-d-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep–wake organization

Cited by 48 publications

References 69 publications

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

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

Essential Role of Dopamine D₂Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice

Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease and Frontotemporal Degeneration

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Neurotoxic N-methyl-d-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep–wake organization

Cited by 48 publications

References 69 publications

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

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

Essential Role of Dopamine D2Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice

Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease and Frontotemporal Degeneration

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Essential Role of Dopamine D₂Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice