Evidence map›Paper›PMID 28218241›Full record

ArticleScientific reports2017

Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development.

Christopher G Dengler, Cuiyong Yue, Hajime Takano, Douglas A Coulter

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

26 citing papers in PubMed, 42 citations in OpenAlex.

  1. Cell-Intrinsic Regulation of Epilepsy-Associated Pathology by mTORC1 and mTORC2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  2. Article
  3. Article
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  7. Intrinsic and Synaptic Contributions to Repetitive Spiking in Dentate Granule Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  12. Article
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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

4 authors at 2 institutions in 1 country.

Christopher G DenglerDepartments of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Cuiyong YueThe Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Hajime TakanoThe Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Douglas A CoulterDepartments of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

Neuronal Circuit Mechanisms of EpileptogenesisR01NS038572 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI COULTER, DOUGLAS A · 1999 to 2022
$8.0M
The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI YUDKOFF, MARC · 2016 to 2020
$6.3M
Normal and Pathological Function of the Dentate GyrusR01NS082046 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Hajime Takano · 2012 to 2026
$6.1M
PHYSIOLOGY OF STATUS EPILEPTICUS IN VITROR01NS032403 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI COULTER, DOUGLAS A · 1994 to 2012
$2.7M
NICHD NIH HHS U54 HD086984NINDS NIH HHS R01 NS032403NINDS NIH HHS R01 NS038572NINDS NIH HHS R01 NS082046
6 · The paper itself

Abstract

In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses.

Indexed as

Neural InhibitionAnimalsChloridesDentate GyrusDisease Models, AnimalEpilepsygamma-Aminobutyric AcidGlutamineMiceNeuronsChloridesgamma-Aminobutyric AcidGlutamine

Identifiers

PMID28218241
PMCPMC5316990
OpenAlexW2589649940

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.