Serotonin at the Laterodorsal Tegmental Nucleus Suppresses Rapid-Eye-Movement Sleep in Freely Behaving Rats

Serotonin [5-hydroxytryptamine (5-HT)] is believed to play an important inhibitory role in the regulation of rapid-eye-movement (REM) sleep. 5-HT may exert this effect on neurons of the laterodorsal tegmental (LDT) nuclei that are implicated as important in the generation of REM sleep and phasic REM events such as ponto-geniculo-occipital (PGO) waves and respiratory variability. In rat brainstem in vitro, 5-HT hyperpolarizes and inhibits the bursting properties of LDT neurons assumed to be involved in generating REM sleep and PGO waves. This study tests the hypothesis that in vivo 5-HT at the LDT nuclei suppresses REM sleep and phasic REM events. Ten rats were implanted with bilateral cannulae aimed at the LDT and with electrodes for recording the electroencephalogram, neck electromyogram, PGO waves, and diaphragm electromyogram. During REM sleep, 5-HT (100 nl; 1–1.5 mm), saline, or sham microinjections were performed; repeated microinjections were separated by ∼1 hr. After the first microinjection, REM sleep as a percent of the total sleep time was reduced with 5-HT (mean percent REM, 19.9 ± 2.5% for 5-HT vs 26.8 ± 2.4% for saline; p = 0.02). REM duration was reduced by 37% with 5-HT (p = 0.01), but REM episode frequency was changed less consistently (p = 0.21), suggesting that 5-HT mainly disrupted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no effect on the amount or variability of REM PGO activity (p > 0.740) or on the mean or coefficient of variation of REM respiratory rate (p > 0.11). With subsequent microinjections, the effects of 5-HT on REM sleep were similar. A dose-dependent REM sleep suppression with 5-HT was observed in five rats tested. These data suggest that in vivo 5-HT at the LDT nuclei suppresses REM sleep expression. Although 5-HT did not disproportionately reduce the occurrence of phasic events within REM, total REM phasic activity was reduced because of less REM sleep after 5-HT.

• Publication year

  1997

• Venue

  Journal of Neuroscience

• Publication date

  1997-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.17-19-07541.1997PMID 9295399PMCID PMC6573466
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats

  2004cited by this paper
• Elicited PGO waves in rats: lack of 5-HT1A inhibition in putative pontine generator region.

  1996influential reference
• Chronic low-amplitude electrical stimulation of the laterodorsal tegmental nucleus of freely moving cats increases REM sleep.

  1996cited by this paper
• Microdialysis perfusion of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH- DPAT) in the dorsal raphe nucleus decreases serotonin release and increases rapid eye movement sleep in the freely moving cat

  1996influential reference
• Amygdaloid control of alerting and behavioral arousal in rats: involvement of serotonergic mechanisms.

  1995cited by this paper
• Brainstem neuromodulation and REM sleep

  1995influential reference
• Photographic Atlas of the Rat Brain: The Cell and Fiber Architecture Illustrated in Three Planes with Stereotaxic Coordinates

  1995cited by this paper
• Scoring transitions to REM sleep in rats based on the EEG phenomena of pre-REM sleep: an improved analysis of sleep structure.

  1994influential reference
• Central administration of two 5-HT receptor agonists: effect on REM sleep initiation and PGO waves.

  1994influential reference
• Serotonergic synaptic input to cholinergic neurons in the rat mesopontine tegmentum.

  1994cited by this paper
• Serotonergic and cholinergic inhibition of mesopontine cholinergic neurons controlling REM sleep: an in vitro electrophysiological study.

  1994influential reference
• Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation.

  1993influential reference
• Mutual interactions among cholinergic, noradrenergic and serotonergic neurons studied by ionophoresis of these transmitters in rat brainstem nuclei.

  1993cited by this paper
• Firing of 'possibly' cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness.

  1992influential reference
• Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro.

  1992influential reference
• Spontaneous phasic activity in the brain: differences between waves in lateral geniculate and central lateral nuclei across sleep states

  1992cited by this paper
• 5-Hydroxytryptamine receptors.

  1992cited by this paper
• Evocation of postural atonia and respiratory depression by pontine carbachol in the decerebrate rat.

  1992cited by this paper
• Cholinergic Pontine Mechanisms Causing State-Dependent Respiratory Depression

  1992cited by this paper
• EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association.

  1992cited by this paper
• Paradoxical sleep and its chemical/structural substrates in the brain.

  1991cited by this paper
• Ventilation during early and late rapid-eye-movement sleep in normal humans.

  1991cited by this paper
• Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems

  1990cited by this paper
• Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves

  1990cited by this paper
• Brainstem Control of Wakefulness and Sleep

  1990cited by this paper
• Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra reticulata.

  1990cited by this paper
• Cholinoceptive pontine reticular mechanisms cause state-dependent respiratory changes in the cat.

  1989cited by this paper
• [5-Hydroxytryptamine receptors].

  1989cited by this paper
• Control of breathing during sleep.

  1984cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983influential reference
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper
• Spontaneous and elicited PGO spikes in rats.

  1981cited by this paper
• Single unit recordings in the nuclei raphe dorsalis and magnus during the sleep-waking cycle of semi-chronic prepared cats.

  1981cited by this paper
• Brain stem PGO-on cells projecting directly to the cat dorsal lateral geniculate nucleus.

  1980cited by this paper
• Rapid eye movement sleep PGO-type waves are present in the dorsal pons of the albino rat.

  1980cited by this paper
• Medullary respiratory neuron activity: relationship to tonic and phasic REM sleep.

  1980cited by this paper
• Metencephalic localization of ponto-geniculo-occipital waves in the albino rat.

  1980cited by this paper
• Demonstration of ponto-geniculo-occipital waves in the albino rat.

  1980cited by this paper
• Raphe unit activity in freely moving cats: correlation with level of behavioral arousal.

  1979cited by this paper
• Ponto-geniculo-occipital (PGO) burst neurons: correlative evidence for neuronal generators of PGO waves.

  1978cited by this paper
• Control of breathing during sleep.

  1978cited by this paper
• Dorsal raphe neurons: depression of firing during sleep in cats.

  1976cited by this paper
• Neuronal excitability modulation over the sleep cycle: a structural and mathematical model.

  1975cited by this paper
• The role of the raphe nuclei in the regulation of ponto-geniculo-occipital wave activity.

  1973cited by this paper
• Electrophysiological and behavioral effects of electrical stimulation of the raphe nuclei in cats.

  1973cited by this paper
• Brain stem serotonin depletion and ponto-geniculo-occipital wave activity in the cat treated with reserpine.

  1972cited by this paper
• Neurochemical bases of the PGO wave.

  1972cited by this paper
• BRES 19361 5-HT 2 receptor immunoreactivity on cholinergic neurons of the pontomesencephalic tegmentum shown by double immunofluorescence

  year unknowncited by this paper

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  2020cites this paper
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  2018cites this paper
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  2015cites this paper
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• Control of sleep and wakefulness.

  2012cites this paper
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• Activation of inactivation process initiates rapid eye movement sleep.

  2012cites this paper
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  2011cites this paper
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  2011cites this paper
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  2011cites this paper
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  2010cites this paper
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  2010cites this paper
• The Effects of Sleep Hypoxia on Coagulant Factors and Hepatic Inflammation in Emphysematous Rats

  2010influential citation
• Analysis of the effects of neuromodulators on the generation of spontaneous pontine-geniculate-occipital (PGO) waves

  2010cites this paper
• Ultrastructural characterization of relationship between serotonergic and GABAergic structures in the ventral part of the oral pontine reticular nucleus.

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• Section V. Serotonin system.

  2005cites this paper
• Dreaming: a neuroimaging view

  2005cites this paper
• A study of the brain structures involved in the acute effects of fluoxetine on REM sleep in the rat.

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• Laterodorsal tegmental projections to identified cell populations in the rat ventral tegmental area

  2005cites this paper
• Contribution of the "knock-out" technology to understanding the role of serotonin in sleep regulations.

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  2004cites this paper
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  2004cites this paper
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  2004cites this paper
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• Brainstem structures responsible for paradoxical sleep onset and maintenance.

  2004cites this paper
• Development of REM sleep drive and clinical implications.

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• REM Sleep Effects as a Biomarker for the Effects of Antidepressants in Healthy Volunteers

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  2003cites this paper
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  2002cites this paper
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