Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and waking in the rat

Miller, Joseph D.; Farber, Jorge; Gatz, Pam; Roffwarg, Howard P.; German, Dwight C.

doi:10.1016/0006-8993(83)91101-0

Cited by 259 publications

(148 citation statements)

References 28 publications

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“…Additionally, muscle activity is primarily inhibited during REM sleep, with the exception of eye movements in humans and whisker movements in rodents (Aserinsky and Kleitman, 1953;Dement and Kleitman, 1957a,b;Jouvet et al, 1959). Although the mean firing rate of dopaminergic neurons does not change significantly throughout the sleep-wake cycle (Miller et al, 1983), REM sleep is also characterized by an increase in dopamine release (Maloney et al, 2002;Lena et al, 2005). Together with the sleep disturbances displayed by individuals with altered dopaminergic transmission, this evidence further supports the hypothesis that dopamine plays an important role in regulating the sleepwake cycle.…”

Section: Introductionsupporting

confidence: 58%

Dopaminergic Control of Sleep–Wake States

et al. 2006

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Section: Introductionsupporting

confidence: 58%

Dopaminergic Control of Sleep–Wake States

et al. 2006

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“…Many areas of the brain that are known to promote wakefulness are quiescent during natural sleep (2), but VTA DA neurons have similar mean firing rates over sleep-wake cycles (21,22), suggesting they are not involved in sleep-wake transitions. However, general anesthetics produce a state of profound unresponsiveness that is distinct from natural sleep (for example, rodents do not lose the righting reflex when they sleep).…”

Section: Discussionmentioning

confidence: 99%

“…It was discovered more than three decades ago that the mean firing rates of DA neurons in the VTA and SN do not change appreciably during sleep or wakefulness (21,22), suggesting that they do not play a central role in regulating arousal. As a consequence, most studies of DA networks have focused on other functions such as movement (23), reward (24), and cognition (25).…”

mentioning

confidence: 99%

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor

Dort

Kenny

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

220

179

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Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.anesthesia | ventral tegmental area | dopamine | optogenetics | arousal

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“…Under these "quiet, resting conditions," environmental factors as well as physiological cycles can affect SNr cells and, consequently, change their responsiveness to GLU. Several studies revealed that the activity of SNr neurons is modulated by environmental context (Handel and Glimcher, 2000;Gulley et al, 2002) and by continuous oscillations of the wake-sleep cycle naturally occurring during quiet, resting conditions during day- time recording (Miller et al, 1983). Because the activity of serotonin-containing neurons and serotonin release varies depending on the sleep-wakefulness cycle (for review, see Portas et al, 2000) and because this neurotransmitter has direct postsynaptic effects on SNr neurons via 5-HT 2c receptors and is involved in presynaptic regulation of GABA release via 5-HT 1b receptors (Rick et al, 1995;Stanford and Lacey, 1996), fluctuations in serotonin activity may be a factor determining the variability of basal activity and GLU responsiveness of SNr neurons.…”

Section: Discussionmentioning

confidence: 99%

GABA, Not Glutamate, Controls the Activity of Substantia Nigra Reticulata Neurons in Awake, Unrestrained Rats

Windels

Kiyatkin²

2004

J. Neurosci.

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Substantia nigra pars reticulata (SNr) receives both GABAergic and glutamatergic (GLU) inputs that are believed to act together to regulate neuronal activity in this structure. To examine the role of these inputs, single-unit recording was coupled with iontophoresis of GLU and GABA in rats under two conditions: awake, unrestrained and under chloral hydrate anesthesia. Although GABA potently inhibited SNr cells in both conditions, freely moving rats showed lower sensitivity than anesthetized animals. Likewise, GLU effectively induced excitations in most SNr neurons in anesthetized animals but was much less effective in awake, unrestrained animals in terms of both the number of sensitive cells and the magnitude of GLU-induced excitation. These findings, along with consistent excitations induced by bicuculline in awake, unrestrained rats, suggest that modulation of GABA inhibitory input, not the opposing actions of GLU and GABA, is the primary factor that regulates the activity state of SNr neurons.

show abstract

Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and waking in the rat

Cited by 259 publications

References 28 publications

Dopaminergic Control of Sleep–Wake States

Dopaminergic Control of Sleep–Wake States

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

GABA, Not Glutamate, Controls the Activity of Substantia Nigra Reticulata Neurons in Awake, Unrestrained Rats

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