Evidence map›Paper›PMID 36170177›Full record

ArticleSleep2022

Glutamatergic pedunculopontine tegmental neurons control wakefulness and locomotion via distinct axonal projections.

Daniel Kroeger, Jack Thundercliffe, Alex Phung, Roberto De Luca, Carolyn Geraci, Samuel Bragg, Kayleen J McCafferty, Sathyajit S Bandaru, Elda Arrigoni, Thomas E Scammell

Open access · greenAbstract read
In one paragraph

Article in Sleep, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Daniel KroegerDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8020-4972
Jack ThundercliffeDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5920-9034
Alex PhungDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Roberto De LucaDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8105-426X
Carolyn GeraciDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Samuel BraggDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Kayleen J McCaffertyDepartment of Anatomy, Physiology, and Pharmacology, Auburn University, Auburn, AL, USA.
Sathyajit S BandaruDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Elda ArrigoniDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Thomas E ScammellDepartment of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Beth Israel Deaconess Medical Center · USAuburn University · US

Funding

Project 5: Novel strategies to prevent opioid-induced hypoventilation during sleep and identification of underlying mechanismsP01HL149630 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Roberto De Luca · 2020 to 2026
$22.3M
TRAINING IN SLEEP, CIRCADIAN &RESPIRATORY NEUROBIOLOGYT32HL007901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Charles A Czeisler · 1998 to 2026
$18.5M
NHLBI NIH HHS P01 HL149630NHLBI NIH HHS T32 HL007901NIH HHS HL095491
6 · The paper itself

Abstract

STUDY

objectivesThe pedunculopontine tegmental (PPT) nucleus is implicated in many brain functions, ranging from sleep/wake control and locomotion, to reward mechanisms and learning. The PPT contains cholinergic, GABAergic, and glutamatergic neurons with extensive ascending and descending axonal projections. Glutamatergic PPT (PPTvGlut2) neurons are thought to promote wakefulness, but the mechanisms through which this occurs are unknown. In addition, some researchers propose that PPTvGlut2 neurons promote locomotion, yet even though the PPT is a target for deep brain stimulation in Parkinson's disease, the role of the PPT in locomotion is debated. We hypothesized that PPTvGluT2 neurons drive arousal and specific waking behaviors via certain projections and modulate locomotion via others.

methodsWe mapped the axonal projections of PPTvGlut2 neurons using conditional anterograde tracing and then photostimulated PPTvGlut2 soma or their axon terminal fields across sleep/wake states and analyzed sleep/wake behavior, muscle activity, and locomotion in transgenic mice.

resultsWe found that stimulation of PPTvGlut2 soma and their axon terminals rapidly triggered arousals from non-rapid eye movement sleep, especially with activation of terminals in the basal forebrain (BF) and lateral hypothalamus (LH). With photoactivation of PPTvGlut2 terminals in the BF and LH, this wakefulness was accompanied by locomotion and other active behaviors, but stimulation of PPTvGlut2 soma and terminals in the substantia nigra triggered only quiet wakefulness without locomotion.

conclusionsThese findings demonstrate the importance of the PPTvGluT2 neurons in driving various aspects of arousal and show that heterogeneous brain nuclei, such as the PPT, can promote a variety of behaviors via distinct axonal projections.

Indexed as

Basal ForebrainWakefulnessAnimalsAxonsMiceNeuronsSleeplocomotionNREM sleeppedunculopontinephotostimulationwake

Identifiers

PMID36170177
PMCPMC9742893
OpenAlexW4297488517

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.