Evidence map›Paper›PMID 40632649›Full record

ArticleEpilepsia open2025

Non-synaptic interictal epileptiform discharges propagating from CA3 to CA1 induce synaptic depression in the hippocampus.

Lauren H Zukowski, Jiaxin Zhou, Snigdha Chawla, Chia-Chu Chiang, Dominique M Durand

Abstract read
In one paragraph

Article in Epilepsia open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. 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

5 authors.

Lauren H ZukowskiDepartment of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.
Jiaxin ZhouDepartment of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.ORCID https://orcid.org/0009-0004-7907-6776
Snigdha ChawlaDepartment of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.
Chia-Chu ChiangDepartment of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.ORCID https://orcid.org/0000-0002-9021-2300
Dominique M DurandDepartment of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.

Funding

Detection and Control of EpilepsyR01NS060757 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2008 to 2016
$2.8M
Seizure control by electric field controlR01NS121084 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2021 to 2025
$1.9M
Cellular and Neural Network Mechanism of Transcranial Electric StimulationR01NS124592 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2021 to 2025
$1.8M
Analysis &Control of NonSynaptic Epileptiform ActivityR01NS040785 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2001 to 2004
$913k
NIH HHS R01NS121084NIH HHS R01NS124592NINDS NIH HHS R01 NS040785NINDS NIH HHS R01 NS060757NINDS NIH HHS R01 NS121084NINDS NIH HHS R01 NS124592
6 · The paper itself

Abstract

objectivePatients with epilepsy contend with memory impairment associated with the prevalence of interictal epileptiform discharges (IEDs). IEDs can propagate without synaptic transmission in both in vivo and in vitro rodent hippocampi. We focused our investigation on the effects of these non-synaptically propagating IEDs on synaptic plasticity. Specifically, we tested the hypothesis that such IEDs generate long-term depression.

methodsIEDs were induced in mouse longitudinal hippocampal slices (i.e., cut along the septotemporal axis of the hippocampus) using 4-aminopyridine (4-AP). Changes in amplitudes and slopes of the population excitatory evoked postsynaptic potentials (pEPSPs) were measured from the CA1 apical dendrite following stimulation at the Schaffer collaterals. Direct current stimulation (DCS) was applied to study the interaction between applied electric fields and IED-induced synaptic plasticity.

resultsFollowing long-term potentiation, 4-AP-induced IEDs were observed to propagate along the slice and in the slice generated significant depression as evidenced by a significant decrease in pEPSP slope. Analysis revealed an inverse relationship between IED frequency and synaptic depression magnitude, with lower-frequency IEDs producing more pronounced synaptic downregulation. In addition, anodal DCS effectively canceled the LTD-like effect induced by 4-AP IEDs, restoring synaptic strength. In contrast, cathodal DCS failed to modify or reverse the 4-AP-induced synaptic depression. SIGNIFICANCE: This study provides insights into how non-synaptic IEDs contribute to synaptic plasticity alterations, offering a potential mechanism for memory impairment in epilepsy. The results highlight the therapeutic potential of anodal DCS for mitigating IED-related cognitive deficits. PLAIN LANGUAGE SUMMARY: People with epilepsy often have memory problems, which may be linked to abnormal brain activity called interictal epileptiform discharges (IEDs). In this study, we found that these discharges can weaken connections between brain cells, possibly explaining some memory issues. We also found that applying a gentle electrical current to the brain (called anodal direct current stimulation) could prevent this weakening. These results suggest a possible new approach to reduce memory problems in epilepsy.

Indexed as

CA1 Region, HippocampalCA3 Region, HippocampalEpilepsyLong-Term Synaptic Depression4-AminopyridineAnimalsElectric StimulationExcitatory Postsynaptic PotentialsLong-Term PotentiationMaleMiceMice, Inbred C57BL4-AminopyridineDCSIEDsnon‐synaptic propagationsynaptic depression

Identifiers

PMID40632649
PMCPMC12362161

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.