Evidence map›Paper›PMID 40799534›Full record

ArticlebioRxiv : the preprint server for biology2025

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

Emma E Macdonald, Jun Ma, Di Liu, Kai Yu, Michael E Authement, Yan Leng, Hannah C Goldbach, Veronica A Alvarez, Bruno B Averbeck, Mario A Penzo

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Emma E MacdonaldSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.
Jun MaSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.
Di LiuSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.
Kai YuSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.
Michael E AuthementSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD 20892.
Yan LengSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.
Hannah C GoldbachSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD 20892.
Veronica A AlvarezSection on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD 20892.
Bruno B AverbeckLaboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD 20892.
Mario A PenzoSection on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892.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
Dissecting the stress circuits of the paraventricular nucleus of the thalamusZIAMH002950 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI PENZO, MARIO · 2016 to 2025
$17.5M
Intramural NIH HHS ZIA MH002928Intramural NIH HHS ZIA MH002950
6 · The paper itself

Abstract

Motivated behavior is often framed in terms of biologically grounded outcomes, such as food or threat. Yet many motivated actions, like the pursuit of safety or agency, depend on outcomes that lack explicit sensory value and must instead be inferred from experience. Here, we identify a thalamostriatal circuit mechanism by which such internally constructed outcomes acquire motivational value. In mice performing an active avoidance task, neurons in the paraventricular thalamus (PVT) projecting to the nucleus accumbens (NAc) develop a safety-encoding signal that emerges following successful avoidance. This signal is experience-dependent and value-sensitive, diminishing upon devaluation of the instrumental contingency. Selective silencing of the PVT→NAc projection at safety onset disrupts avoidance persistence without impairing action-outcome learning, as confirmed by computational modeling of value updating based on prediction error. Mechanistically, PVT input recruits cholinergic interneurons (CINs) to modulate dopamine release and this influence depends on synaptic potentiation mediated by GluA2-lacking AMPA receptor insertion at PVT-CIN synapses. Disrupting this plasticity selectively impairs the avoidance response by blunting the motivational value of safety without affecting acquisition. These findings reveal how thalamic circuits assign value to abstract, internal outcomes, providing a framework for understanding how goals like safety are inferred, stabilized, and rendered behaviorally effective.

Identifiers

PMID40799534
PMCPMC12340825

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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.