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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.
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http://dx.doi.org/10.1101/2025.08.04.668532 | DOI Listing |
J Appl Clin Med Phys
September 2025
Clinical Imaging Physics Group, Duke University Health System, Durham, North Carolina, USA.
Introduction: Medical physicists play a critical role in ensuring image quality and patient safety, but their routine evaluations are limited in scope and frequency compared to the breadth of clinical imaging practices. An electronic radiologist feedback system can augment medical physics oversight for quality improvement. This work presents a novel quality feedback system integrated into the Epic electronic medical record (EMR) at a university hospital system, designed to facilitate feedback from radiologists to medical physicists and technologist leaders.
View Article and Find Full Text PDFJ Med Case Rep
September 2025
Department of Anesthesiology, LMU University Hospital Munich LMU, Marchioninistrasse 15, 81377, Munich, Germany.
Background: The treatment of critically ill patients in intensive care units is becoming increasingly complex. For example, organ transplants are regularly carried out, the recipients are seriously ill, and the postoperative course can be complicated. This is why organ replacement and hemadsorption procedures are becoming increasingly important.
View Article and Find Full Text PDFEur J Med Res
September 2025
Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Nuclear receptors (NRs) are a superfamily of ligand-activated transcription factors that regulate gene expression in response to metabolic, hormonal, and environmental signals. These receptors play a critical role in metabolic homeostasis, inflammation, immune function, and disease pathogenesis, positioning them as key therapeutic targets. This review explores the mechanistic roles of NRs such as PPARs, FXR, LXR, and thyroid hormone receptors (THRs) in regulating lipid and glucose metabolism, energy expenditure, cardiovascular health, and neurodegeneration.
View Article and Find Full Text PDFBMC Med Ethics
September 2025
Dept of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.