Evidence map›Paper›PMID 37797581›Full record

ArticleNeuron2023

An inhibitory circuit-based enhancer of DYRK1A function reverses Dyrk1a-associated impairment in social recognition.

Yu-Tzu Shih, Jason Bondoc Alipio, Amar Sahay

Open access · hybridAbstract read
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.3field-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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Epigenetic treatment of synaptic and behavioral deficits in Dyrk1a-mutant mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  4. Review
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  11. Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition.Autism research : official journal of the International Society for Autism Research · 2025
    Article
  12. Upregulated inwardly rectifying KJournal of biomedical research · 2025
    Article
  13. Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Yu-Tzu ShihCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; BROAD Institute of Harvard and MIT, Cambridge, MA, USA.
Jason Bondoc AlipioCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; BROAD Institute of Harvard and MIT, Cambridge, MA, USA.
Amar SahayCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; BROAD Institute of Harvard and MIT, Cambridge, MA, USA. Electronic address: asahay@mgh.harvard.edu.
Broad Institute · US

Funding

Targeting neurogenesis-inhibition coupling to improve memory in aging\Diversity SupplementR01AG076612 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Amar Sahay · 2022 to 2026
$3.8M
Contributions of hippocampal oxytocin receptors to social recognitionR01MH111729 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SAHAY, AMAR · 2018 to 2022
$2.4M
Hippocampal synaptic and circuit mechanisms mediating Dyrk1a functions in social cognitionR01MH131652 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Amar Sahay · 2023 to 2026
$2.4M
NIA NIH HHS R01 AG076612NIMH NIH HHS R01 MH111729NIMH NIH HHS R01 MH131652
6 · The paper itself

Abstract

Heterozygous mutations in the dual-specificity tyrosine phosphorylation-regulated kinase 1a (Dyrk1a) gene define a syndromic form of autism spectrum disorder. The synaptic and circuit mechanisms mediating DYRK1A functions in social cognition are unclear. Here, we identify a social experience-sensitive mechanism in hippocampal mossy fiber-parvalbumin interneuron (PV IN) synapses by which DYRK1A recruits feedforward inhibition of CA3 and CA2 to promote social recognition. We employ genetic epistasis logic to identify a cytoskeletal protein, ABLIM3, as a synaptic substrate of DYRK1A. We demonstrate that Ablim3 downregulation in dentate granule cells of adult heterozygous Dyrk1a mice is sufficient to restore PV IN-mediated inhibition of CA3 and CA2 and social recognition. Acute chemogenetic activation of PV INs in CA3/CA2 of adult heterozygous Dyrk1a mice also rescued social recognition. Together, these findings illustrate how targeting DYRK1A synaptic and circuit substrates as "enhancers of DYRK1A function" harbors the potential to reverse Dyrk1a haploinsufficiency-associated circuit and cognition impairments.

Indexed as

Autism Spectrum DisorderAnimalsBrainDyrk KinasesMiceMossy Fibers, HippocampalParvalbuminsRecognition, PsychologySynapsesDyrk KinasesParvalbuminsAblim3autism spectrum disorderCA2CA3dentate gyrusDyrk1aepistasisfeedforward inhibitionhippocampusparvalbumin interneuronsocial cognition

Identifiers

PMID37797581
PMCPMC10575685
OpenAlexW4387332701

What OpenQuestion holds

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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.