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Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder.

Overview

Authors: Alina Aaltonen1, Jone Razquin1, Daniel R. Garton1, Julia Oyrer1, Chiara Criscuolo2, Ori J. Lieberman3, Eric Klann4, Anders Borgkvist1, Emanuela Santini1
ORCID iDs: Daniel R. Garton
  1. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
  2. Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
  3. Department of Neurology, University of California, San Francisco, CA, USA
  4. Center for Neural Science, New York University, New York, NY, USA
Institutions: Karolinska Institutet (Sweden); Columbia University Irving Medical Center (United States); Columbia University (United States); University of California, San Francisco (United States); New York University (United States)
Journal: iScience, volume 29, issue 9, article 117278
Dates: received 19 March 2026; accepted 5 August 2026; published online 3 September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.117278 · PMID 42733661 · PMCID PMC13571666 · OpenAlex W7140159323
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.2139/ssrn.6460219
Status: code on request
Categories: histology / microscopy (modality), mouse (organism), autism (population), cellular / molecular (subfield)
Methods: Statistics, Preprocessing, fMRI & imaging, Single-unit activity, calcium imaging
Keywords: autism spectrum disorder, eIF4E, striatum, synaptic plasticity, long-term potentiation, spiny projection neurons, dendritic spines, NMDA receptors, dopamine, translational control
Topic: Genetics and Neurodevelopmental Disorders (Genetics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Knut and Alice Wallenberg Foundation; Wallenberg Academy (KAW 2017-0169, 2020-0054); Vetenskapsrådet (2016-02758, 2023-02943, 2016-03129, 2024-03684); Olle Engkvist Stiftelse; Åhlén’s Foundation; Magn. Bergvall’s Foundation; Strategic Research Program in Neuroscience; StratNeuro; Karolinska Institutet
Citations: not cited yet (Europe PMC); 144 references in the paper
Research resources: Goat anti-rabbit Alexa Fluor 568 RRID:AB_143157, RRID:AB_2209751, Goat anti-mouse Alexa Fluor 488 RRID:AB_2534069, pGP-AAV-syn-FLEX-jGCaMP7s-WPRE RRID:Addgene_104491, pAAV-hSyn-hChR2(H134R)-mCherry RRID:Addgene_26976, Mouse: Drd1a-TdTomato RRID:IMSR_JAX:016204, Mouse: Tg(Drd2-EGFP)S118Gsat/Mmnc RRID:MMRRC_000230-UNC, GraphPad Prism RRID:SCR_002798, pClamp 11 RRID:SCR_011323, lme4 RRID:SCR_015654, lmerTest RRID:SCR_015656, Stimfit RRID:SCR_016050, Multiclamp 700B amplifier RRID:SCR_018455, Emmeans RRID:SCR_018734, DMC-BrainMAP Napari plugin RRID:SCR_027433

Abstract

Autism spectrum disorder (ASD) is associated with deficits in synaptic plasticity across multiple brain regions. While striatal dysfunction is observed in several ASD mouse models, the effects of ASD-associated genes on striatal plasticity remain poorly understood. We previously showed that overexpression of the Simons Foundation Autism Research Initiative (SFARI) ASD risk gene eukaryotic initiation factor 4E (eIF4E) in transgenic (eIF4E-TG) mice produces ASD-like behaviors and impairs dorsal striatal dopamine release. Here, we examined whether eIF4E overexpression alters striatal synaptic transmission and plasticity. eIF4E-TG mice exhibited increased dendritic spine density, elevated AMPA- and NMDA receptor-mediated miniature excitatory postsynaptic current (mEPSC) frequency, and reduced AMPA mEPSC amplitude. In addition, spiny projection neurons (SPNs) showed enhanced induction and magnitude of NMDA receptor-dependent long-term potentiation (LTP) that was not prevented by D1 or D2 receptor antagonism. Finally, depolarization-evoked somatic and dendritic Ca2+ signals were altered in eIF4E-TG SPNs. Together, these findings indicate that eIF4E overexpression biases striatal neurons toward NMDA receptor-dependent LTP.

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.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data and code availability

• The data reported in this paper will be shared by the lead contact upon request. • All original code used for linear mixed-effects model analyses is available in this paper’s supplemental information (Data S1). The corresponding data table arrangement used for these analyses is provided in Data S2. • Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 3, 28 September 2026

  • Authors: added Daniel R. Garton (0000-0002-5822-9233); removed Daniel R. Garton

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 10 keywords, 9 funders, 142 references, 15 RRIDs.

Cite

This paper

Aaltonen, A., Razquin, J., Garton, D. R., Oyrer, J., Criscuolo, C., Lieberman, O. J., Klann, E., Borgkvist, A., & Santini, E. (2026). Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder. iScience, 29(9), 117278. https://doi.org/10.1016/j.isci.2026.117278

BibTeX

@article{aaltonen2026altered,
author = {Aaltonen, Alina and Razquin, Jone and Garton, Daniel R. and Oyrer, Julia and Criscuolo, Chiara and Lieberman, Ori J. and Klann, Eric and Borgkvist, Anders and Santini, Emanuela},
title = {{Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder}},
journal = {iScience},
year = {2026},
month = sep,
volume = {29},
number = {9},
pages = {117278},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.117278},
url = {https://doi.org/10.1016/j.isci.2026.117278},
pmid = {42733661},
pmcid = {PMC13571666}
}

RIS

TY - JOUR
AU - Aaltonen, Alina
AU - Razquin, Jone
AU - Garton, Daniel R.
AU - Oyrer, Julia
AU - Criscuolo, Chiara
AU - Lieberman, Ori J.
AU - Klann, Eric
AU - Borgkvist, Anders
AU - Santini, Emanuela
TI - Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/09/03
VL - 29
IS - 9
SP - 117278
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.117278
UR - https://doi.org/10.1016/j.isci.2026.117278
LA - en
ER -

CSL-JSON

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