{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA. emma.macdonald@nih.gov",
    "Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD 20892",
    "Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China",
    "Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA",
    "Section on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD 089",
    "Section on Neurobiology of Compulsive Behaviors, National Institute of Mental Health, Bethesda, MD, USA",
    "State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China",
    "Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD 20892",
    "Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD, USA. averbeckbb@mail.nih.gov",
    "Section on the Neural Circuits of Emotion and Motivation, National Institute of Mental Health, Bethesda, MD, USA. mario.penzo@nih.gov"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Emma E. Macdonald"
    },
    {
      "affs": [
        2,
        3,
        1
      ],
      "name": "Jun Ma",
      "orcid": "0000-0002-1874-2382"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Di Liu"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Kai Yu",
      "orcid": "0000-0002-9198-2833"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Rachel A. Walker"
    },
    {
      "affs": [
        5,
        1
      ],
      "name": "Michael E. Authement",
      "orcid": "0000-0001-7253-5782"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yan Leng"
    },
    {
      "affs": [
        5,
        4
      ],
      "name": "Hannah C Goldbach",
      "orcid": "0000-0002-5697-4694"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Guochuan Li",
      "orcid": "0009-0000-6837-9780"
    },
    {
      "affs": [
        6,
        1
      ],
      "name": "Yulong Li",
      "orcid": "0000-0002-9166-9919"
    },
    {
      "affs": [
        5
      ],
      "name": "Veronica A. Alvarez",
      "orcid": "0000-0003-2611-8675"
    },
    {
      "affs": [
        8
      ],
      "name": "Bruno B. Averbeck",
      "orcid": "0000-0002-3976-8565"
    },
    {
      "affs": [
        9
      ],
      "name": "Mario Alexander Penzo",
      "orcid": "0000-0002-5368-1802"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/44yxb15yqhp59.bib",
  "cited_by": 8,
  "doi": "10.1038/s41467-026-73906-3",
  "fulltext_url": null,
  "id": "44yxb15yqhp59",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-73906-3",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2805|Memory and Neural Mechanisms"
    ]
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  "openalex": "W4412951732",
  "pdf_url": "https://www.nature.com/articles/s41467-026-73906-3.pdf",
  "pmcid": "PMC12340825",
  "pmid": "40799534",
  "published": "2026-06-04",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/44yxb15yqhp59.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:53Z",
      "native_id": "W4412951732",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-73906-3"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Memory and Neural Mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "A synaptic mechanism for encoding the learned value of action-derived safety",
  "title_text": "A synaptic mechanism for encoding the learned value of action-derived safety",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:12Z",
  "url": "https://research.draconitic.com/paper/44yxb15yqhp59",
  "venue": "Nature Communications",
  "versions": []
}