Evidence map›Paper›PMID 30543800›Full record

ArticleExperimental neurology2019

Mechanisms of decreased cholinergic arousal in focal seizures: In vivo whole-cell recordings from the pedunculopontine tegmental nucleus.

John P Andrews, Zongwei Yue, Jun Hwan Ryu, Garrett Neske, David A McCormick, Hal Blumenfeld

Open access · greenAbstract read
In one paragraph

Article in Experimental neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
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  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Cholinergic Signaling, Neural Excitability, and Epilepsy.Molecules (Basel, Switzerland) · 2021
    Review
  13. A Review of Neuronal Pathways Associated With Consciousness.The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses · 2021
    Review
  14. Article
  15. Review
  16. Article
  17. Up and Down States of Cortical Neurons in Focal Limbic Seizures.Cerebral cortex (New York, N.Y. : 1991) · 2020
    Article
  18. Article
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

6 authors at 1 institution in 1 country.

John P AndrewsDepartment of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Zongwei YueDepartment of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Jun Hwan RyuDepartment of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Garrett NeskeDepartment of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
David A McCormickDepartment of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Hal BlumenfeldDepartment of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: hal.blumenfeld@yale.edu.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Cortical Dynamics and Neural/Behavioral PerformanceR35NS097287 · NINDS · YALE UNIVERSITY · PI MCCORMICK, DAVID · 2017 to 2024
$6.1M
Remote effects of focal hippocampal seizures on neocortical functionR01NS066974 · NINDS · YALE UNIVERSITY · PI HAL BLUMENFELD · 2011 to 2026
$5.5M
Network mechanisms of seizure-induced cardiorespiratory impairmentR01NS096088 · NINDS · YALE UNIVERSITY · PI BLUMENFELD, HAL · 2016 to 2020
$1.8M
NCATS NIH HHS UL1 TR001863NINDS NIH HHS R01 NS066974NINDS NIH HHS R01 NS096088NINDS NIH HHS R35 NS097287
6 · The paper itself

Abstract

Focal limbic seizures often impair consciousness/awareness with major negative impact on quality of life. Recent work has shown that limbic seizures depress brainstem arousal systems, including reduced action potential firing in a key node: cholinergic neurons of the pedunculopontine tegmental nucleus (PPT). In vivo whole-cell recordings have not previously been achieved in PPT, but are used here with the goal of elucidating the mechanisms of reduced PPT cholinergic neuronal activity. An established model of focal limbic seizures was used in rats following brief hippocampal stimulation under light anesthesia. Whole-cell in vivo recordings were obtained from PPT neurons using custom-fabricated 9-10 mm tapered patch pipettes, and cholinergic neurons were identified histologically. Average membrane potential, input resistance, membrane potential fluctuations and variance were analyzed during seizures. A subset of PPT neurons exhibited reduced firing and hyperpolarization during seizures and stained positive for choline acetyltransferase. These PPT neurons showed a mean membrane potential hyperpolarization of -3.82 mV (±0.81 SEM, P < .05) during seizures, and also showed significantly increased input resistance, fewer excitatory post-synaptic potential (EPSP)-like events (P < .05), and reduced membrane potential variance (P < .01). The combination of increased input resistance, decreased EPSP-like events and decreased variance weigh against active ictal inhibition and support withdrawal of excitatory input as the dominant mechanism of decreased activity of cholinergic neurons in the PPT. Further identifying synaptic mechanisms of depressed arousal during seizures may lead to new treatments to improve ictal and postictal cognition.

Indexed as

AnimalsCholine O-AcetyltransferaseElectric StimulationElectrophysiological PhenomenaEpilepsies, PartialExcitatory Postsynaptic PotentialsFemaleHippocampusMembrane PotentialsNeuronsParasympathetic Nervous SystemPatch-Clamp TechniquesPedunculopontine Tegmental NucleusRatsRats, Sprague-DawleySeizuresCholine O-Acetyltransferase

Identifiers

PMID30543800
PMCPMC6503533
OpenAlexW2904517283

What OpenQuestion holds

Textmetadata
LicenceTDM
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.