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

E Emma E. Macdonald J Jun Ma D Di Liu K Kai Yu R Rachel A. Walker M Michael E. Authement Y Yan Leng H Hannah C. Goldbach G Guochuan Li Y Yulong Li V Veronica A. Alvarez B Bruno B. Averbeck (Laboratory of Neuropsychology, National Institute of Mental Health) M Mario A. Penzo

Abstract

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.

Article Details

Volume / Issue Vol. 17, Issue 1
Published June 04, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (13)

E

Emma E. Macdonald

J

Jun Ma

D

Di Liu

K

Kai Yu

R

Rachel A. Walker

M

Michael E. Authement

Y

Yan Leng

H

Hannah C. Goldbach

G

Guochuan Li

Y

Yulong Li

V

Veronica A. Alvarez

B

Bruno B. Averbeck

Laboratory of Neuropsychology, National Institute of Mental Health

M

Mario A. Penzo