Evidence map›Paper›PMID 42243099›Full record

ArticleNature communications2026

A synaptic mechanism for encoding the learned value of action-derived safety.

Emma E Macdonald, Jun Ma, Di Liu, Kai Yu, Rachel A Walker, Michael E Authement, Yan Leng, Hannah C Goldbach, Guochuan Li, Yulong Li and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2026. 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. Article
  2. Article
  3. Review
  4. Article
  5. Dual cholinergic mechanisms for sculpting striatal dopamine in vivo.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Emma E Macdonald *Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA. emma.macdonald@nih.gov.
Jun Ma *Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA.
Di Liu *Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA.
Kai Yu *Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA.
Rachel A WalkerSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA.
Michael E AuthementSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD, USA.
Yan LengSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA.
Hannah C GoldbachSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD, USA.ORCID 0000-0002-5697-4694
Guochuan LiState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.ORCID 0009-0000-6837-9780
Yulong LiState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.ORCID 0000-0002-9166-9919
Veronica A AlvarezSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD, USA.ORCID 0000-0003-2611-8675
Bruno B AverbeckLaboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD, USA. averbeckbb@mail.nih.gov.ORCID 0000-0002-3976-8565
Mario A PenzoSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA. mario.penzo@nih.gov.ORCID 0000-0002-5368-1802

Funding

Frontal Striatal Systems and Dopamine in Normal and Pathological BehaviorZIAMH002928 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AVERBECK, BRUNO · 2010 to 2025
$29.0M
Intramural NIH HHS ZIA MH002928U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1ZIAMH002950
6 · The paper itself

Abstract

Adaptive behavior requires that behaviorally relevant signals gain access to neural circuits guiding action. The thalamus has long been proposed to regulate information flow to cortical and subcortical systems, yet whether it also tracks internally generated goal signals remains unclear. Here, we show that neurons in the paraventricular thalamus (PVT) projecting to the nucleus accumbens (NAc) encode the motivational value of safety during active avoidance. As mice learn to avoid threat, PVT→NAc neurons develop a signal that emerges selectively at successful avoidance, is experience-dependent, and diminishes following outcome devaluation. Selective silencing of the PVT→NAc pathway at safety onset reduces the motivational value assigned to safety without impairing action-outcome learning. Mechanistically, PVT input engages cholinergic interneurons (CIN) in the NAc to regulate dopamine release via synaptic potentiation mediated by GluA2-lacking AMPA receptors at PVT-CIN synapses. Disrupting this plasticity reduces the motivational impact of safety. These findings identify a thalamostriatal mechanism through which learned goals gain stable access to motivational circuitry.

Indexed as

Avoidance LearningMidline Thalamic NucleiNucleus AccumbensSynapsesAnimalsCholinergic NeuronsDopamineInterneuronsLearningMaleMiceMice, Inbred C57BLMotivationNeural PathwaysNeuronal PlasticityReceptors, AMPADopamineReceptors, AMPA

Identifiers

PMID42243099
PMCPMC13237380

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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.