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Age-dependent axonal dysfunctions and altered sharp-wave ripple oscillations in <i>Scn1a</i> <sup><i>+/-</i></sup> mice.

Overview

Authors: Raquel Lascorz1, Fabian C Roth1
ORCID iDs: Fabian C Roth
  1. Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Institutions: University of Oslo (Norway)
Journal: iScience, volume 29, issue 8, article 116784
Dates: received 29 October 2025; accepted 29 June 2026; published online 21 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.116784 · PMID 42495533 · PMCID PMC13392871 · OpenAlex W7169844728
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: extracellular electrophysiology (units, LFP) (modality), human (organism), mouse (organism), epilepsy (population), systems (subfield)
Methods: Spectral & time-frequency, Statistics, Machine learning
Keywords: Dravet syndrome, sharp wave ripple, SCN1A, NaV1.1, axonal recording, parvalbumin-expressing interneurons, mice
Topic: Cardiac electrophysiology and arrhythmias (Cardiology and Cardiovascular Medicine, Medicine), according to OpenAlex
Funding: Research Council of Norway (315935)
Citations: not cited yet (Europe PMC); 59 references in the paper
Research resources: RRID:IMSR_JAX:007914, Mouse: B6.129P2-Pvalbtm1(cre)Arbr/J RRID:IMSR_JAX:017320, Mouse: 129S-Scn1atm1Kea/Mmjax RRID:MMRRC_037107-JAX, MATLAB RRID:SCR_001622, GraphPad Prism 10 RRID:SCR_002798, pClamp 9.2.1.9 RRID:SCR_011323, Inkscape RRID:SCR_014479, EXT-10F field potential amplifier RRID:SCR_016002, Multiclamp 700B Amplifier RRID:SCR_018455

Abstract

Mice with Scn1a haploinsufficiency replicate symptoms of Dravet syndrome (DS), a rare childhood disease characterized by febrile seizures at an early age. As adults, patients with DS suffer from epilepsy, motor dysfunction, psychological disorders, and cognitive disabilities. Patients with DS carry loss-of-function variants in the SCN1A gene, which encodes the voltage-gated sodium channel subunit NaV1.1. As shown in mice, this subunit is mainly expressed in GABAergic cells, especially parvalbumin-expressing interneurons (PV-INs). Consistent with this, interneuron-driven network activities, such as sharp wave ripple oscillations (SPW-R), are altered in Scn1a-deficient mice. By studying network and PV-IN activity during SPW-R in hippocampal slices from Scn1a+/− mice, we identified age-dependent impairments in ripple oscillation frequencies and in rhythmic action potential (AP) firing in PV-INs, accompanied by alterations in somatic and axonal AP waveforms. This age-dependent increase in hippocampal cellular and network abnormalities may contribute to the persisting cognitive deficits associated with Scn1a haploinsufficiency.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data and code availability

Experimental data are publicly available on the EBRAINS data repository under https://doi.org/10.25493/YEDC-A5S.

This paper does not report original code.

All remaining data and any additional information required to reanalyze the data reported in this paper are available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 2 authors, 7 keywords, 1 funder, 58 references, 9 RRIDs.

Cite

This paper

Lascorz, R., & Roth, F. C. (2026). Age-dependent axonal dysfunctions and altered sharp-wave ripple oscillations in <i>Scn1a</i> <sup><i>+/-</i></sup> mice. iScience, 29(8), 116784. https://doi.org/10.1016/j.isci.2026.116784

BibTeX

@article{lascorz2026age,
author = {Lascorz, Raquel and Roth, Fabian C},
title = {{Age-dependent axonal dysfunctions and altered sharp-wave ripple oscillations in \<i\>Scn1a\</i\> \<sup\>\<i\>+/-\</i\>\</sup\> mice}},
journal = {iScience},
year = {2026},
month = jul,
volume = {29},
number = {8},
pages = {116784},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.116784},
url = {https://doi.org/10.1016/j.isci.2026.116784},
pmid = {42495533},
pmcid = {PMC13392871}
}

RIS

TY - JOUR
AU - Lascorz, Raquel
AU - Roth, Fabian C
TI - Age-dependent axonal dysfunctions and altered sharp-wave ripple oscillations in <i>Scn1a</i> <sup><i>+/-</i></sup> mice
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/07/21
VL - 29
IS - 8
SP - 116784
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.116784
UR - https://doi.org/10.1016/j.isci.2026.116784
LA - en
ER -

CSL-JSON

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