Brain Architecture of Punishment Learning.
Overview
Abstract
Learning from punishment allows animals to suppress actions that produce adverse consequences while maintaining other rewarded behaviors. However, the brain mechanisms of this learning are poorly understood. Here, we combined instrumental behavioral analysis, whole-brain Fos mapping, spatial transcriptomics, computational network analysis, and chemogenetic inhibition in male and female mice. A within-subject yoking procedure showed that suppression depended on the instrumental response–punisher contingency rather than matched shock exposure or embedded pavlovian stimulus–shock relations. Whole-brain Fos network analysis showed marked reorganization of brain-wide Fos correlation structure after punishment learning. Punishment preserved modular, small-world organization characteristic of brain networks while reallocating regional community membership and increasing the centrality of the basolateral amygdala (BLA), zona incerta (ZI), and midbrain tegmentum. Spatial transcriptomics within these regions identified punishment-associated transcriptional programs in BLA glutamatergic neurons, ZI GABAergic neurons, and multiple ventral midbrain GABAergic and dopaminergic populations. In silico deletion predicted that the BLA, ZI, and rostral linear nucleus jointly support punishment learning. Consistent with this, multisite chemogenetic inhibition of these regions impaired punishment learning. Single-region inhibition revealed dissociable contributions of BLA and ZI to within-session and between-session retention of punishment learning. Together, these findings show that punishment learning is supported by a brain network that enables animals to selectively suppress actions that produce adverse consequences.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 6 keywords, 8 MeSH terms, 2 funders, 48 references, 2 RRIDs.
Cite
This paper
Gregory, A. V., Diefenbach, J., Choi, E. A., Soo, J., Chen, J., Killcross, A. S., Jean-Richard-dit-Bressel
BibTeX
@article{gregory2026brai
author = {Gregory, Alexandra V and Diefenbach, James and Choi, Eun A and Soo, Jason and Chen, Jessica and Killcross, A Simon and Jean-Richard-dit-Bressel
title = {{Brain Architecture of Punishment Learning}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2026},
month = sep,
volume = {46},
number = {35},
pages = {e0925262026},
publisher = {Society for Neuroscience},
issn = {0270-6474},
doi = {10.1523/
url = {https://
pmid = {42575705},
pmcid = {PMC13540610}
}
RIS
TY - JOUR
AU - Gregory, Alexandra V
AU - Diefenbach, James
AU - Choi, Eun A
AU - Soo, Jason
AU - Chen, Jessica
AU - Killcross, A Simon
AU - Jean-Richard-dit-Bressel
AU - McNally, Gavan P
TI - Brain Architecture of Punishment Learning
T2 - The Journal of neuroscience : the official journal of the Society for Neuroscience
J2 - J Neurosci
PY - 2026
DA - 2026/
VL - 46
IS - 35
SP - e0925262026
SN - 0270-6474
PB - Society for Neuroscience
DO - 10.1523/
UR - https://
LA - en
ER -
CSL-JSON
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