Evidence map›Paper›PMID 22677032›Full record

ArticleNeurobiology of disease2012

Pyramidal cells accumulate chloride at seizure onset.

Kyle P Lillis, Mark A Kramer, Jerome Mertz, Kevin J Staley, John A White

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

75 citing papers in PubMed, 136 citations in OpenAlex.

  1. Article
  2. GABACellular and molecular neurobiology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Virtual brain twins for stimulation in epilepsy.Nature computational science · 2025
    Article
  7. Massive Activation of GABABiomolecules · 2025
    Review
  8. Article
  9. Article
  10. Downmodulation of Potassium Conductances Induces Epileptic Seizures in Cortical Network Models Via Multiple Synergistic Factors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  11. Review
  12. Article
  13. Phenols and GABAFrontiers in pharmacology · 2024
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

15 more citing papers are in PubMed but not listed here.

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

5 authors at 4 institutions in 1 country.

Kyle P LillisDepartment of Neurology, Massachusetts General Hospital, 114 16th St. #2600, Charlestown, MA 02129, USA. lillis.kyle@mgh.harvard.edu
Mark A Kramer
Jerome Mertz
Kevin J Staley
John A White
Boston University · USHarvard University · USMassachusetts General Hospital · USUniversity of Utah · US

Funding

Real-Time Control System for Biological ExperimentsR01RR020115 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHRISTINI, DAVID J. · 2004 to 2011
$3.9M
Synchronous Activity in Hybrid Neuronal MicrocircuitsR01MH085074 · NIMH · UNIVERSITY OF UTAH · PI WHITE, JOHN A. · 2010 to 2014
$1.7M
NCRR NIH HHS R01 RR020115NIMH NIH HHS R01 MH085074
6 · The paper itself

Abstract

Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABA(A) receptors or by hyperpolarizing the GABA(A) reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABA(A) receptor-mediated chloride influx shifts E(GABA) to produce a positive feedback loop that contributes to the initiation of seizure activity.

Indexed as

4-AminopyridineAcetazolamideAnimalsAnimals, NewbornAnticonvulsantsChloridesDose-Response Relationship, DrugEvoked PotentialsGABA AgentsGlutamate DecarboxylaseGreen Fluorescent ProteinsHippocampusHydrogen-Ion ConcentrationInterneuronsMiceMice, Inbred C57BL4-AminopyridineAcetazolamideAnticonvulsantsChloridesclomeleonGABA AgentsGlutamate Decarboxylaseglutamate decarboxylase 1Green Fluorescent ProteinsPotassium Channel BlockersRecombinant Fusion Proteins

Identifiers

PMID22677032
PMCPMC3392473
OpenAlexW2031003452

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.