Evidence map›Paper›PMID 39983718›Full record

ArticleCell reports2025

Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.

Stephanie A Barnes, Aurore Thomazeau, Peter S B Finnie, Maxwell J Heinrich, Arnold J Heynen, Noburu H Komiyama, Seth G N Grant, Frank S Menniti, Emily K Osterweil, Mark F Bear

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

6 citing papers in PubMed.

  1. Review
  2. Concordant transcriptional and morphological remodeling revealed bybioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. The how and why for multiple forms of hippocampal LTP.Frontiers in synaptic neuroscience · 2026
    Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Stephanie A BarnesThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Aurore ThomazeauThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Peter S B FinnieThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Maxwell J HeinrichThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arnold J HeynenThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Noburu H KomiyamaCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; Simons Initiative for the Developing Brain (SIDB), Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK; The Patrick Wild Centre, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
Seth G N GrantCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; Simons Initiative for the Developing Brain (SIDB), Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
Frank S MennitiMindImmune Therapeutics, Inc., The George & Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA.
Emily K OsterweilCentre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; F.M. Kirby Center for Neurobiology, Translational Neuroscience Center, Department of Neurology, Harvard Medical School, Boston Children's Hospital, Boston, MA 02115, USA.
Mark F BearThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: mbear@mit.edu.

Funding

Polyadenylation induced translation in the brainP01NS039321 · NINDS · BROWN UNIVERSITY · PI FALLON, JUSTIN R · 2000 to 2004
$4.3M
Mechanisms and Functions of FMRP in Neuronal DevelopmentR01HD046943 · NICHD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BEAR, MARK F · 2003 to 2014
$2.9M
Pathophysiology and treatment of fragile X and related disordersR21NS123499 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BEAR, MARK F · 2022 to 2023
$427k
Validating a novel target for correction of pathophysiology in fragile X and TSCR21NS087225 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BEAR, MARK F · 2014 to 2015
$404k
NICHD NIH HHS R01 HD046943NINDS NIH HHS P01 NS039321NINDS NIH HHS R21 NS087225NINDS NIH HHS R21 NS123499
6 · The paper itself

Abstract

N-methyl-D-aspartate (NMDA)-induced spine shrinkage proceeds independently of ion flux and requires the initiation of de novo protein synthesis. Using subtype-selective pharmacological and genetic tools, we find that structural plasticity is dependent on ligand binding to GluN2B-containing NMDA receptors (NMDARs) and signaling via the GluN2B carboxy-terminal domain (CTD). Disruption of non-ionotropic signaling by replacing the GluN2B CTD with the GluN2A CTD leads to an increase in spine density, dysregulated basal protein synthesis, exaggerated long-term depression mediated by G-protein-coupled metabotropic glutamate receptors (mGluR-LTD), and epileptiform activity reminiscent of phenotypes observed in the Fmr1 knockout (KO) model of fragile X syndrome. By crossing the Fmr1 KO mice with animals in which the GluN2A CTD has been replaced with the GluN2B CTD, we observe a correction of these core fragile X phenotypes. These findings suggest that non-ionotropic NMDAR signaling through GluN2B may represent a novel therapeutic target for the treatment of fragile X and related causes of intellectual disability and autism.

Indexed as

Dendritic SpinesFragile X SyndromeNeuronal PlasticityReceptors, N-Methyl-D-AspartateSignal TransductionAnimalsFragile X Messenger Ribonucleoprotein 1Long-Term Synaptic DepressionMaleMiceMice, Inbred C57BLMice, KnockoutPhenotypeProtein DomainsReceptors, Metabotropic GlutamateFmr1 protein, mouseFragile X Messenger Ribonucleoprotein 1NR2B NMDA receptorReceptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateAGSaudiogenic seizuresCP: Neurosciencedendritic spinesepileptogenesisfragile X syndromeFXSGlyx-13long-term depressionLTDmGluR5NMDARnon-ionotropic

Identifiers

PMID39983718
PMCPMC12006837

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Registered trials

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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.