The brain architecture of punishment learning

Abstract

Learning which actions cause harm is essential for survival, yet how the brain transforms this knowledge into adaptive control of behavior remains unclear. We combined whole-brain analysis, multisite chemogenetic silencing, spatial transcriptomics, and longitudinal calcium imaging to map how punishment learning reorganizes brain networks across scales. Learning reshaped mesoscale community organization into a network anchored by the amygdala, subthalamic-hypothalamic zone, and ventral midbrain tegmentum. These regions contributed distinct components of adaptive avoidance and engaged diverse transcriptional programs across multiple neuronal subclasses. Within this network, the amygdala acted as a hub, partitioning action and outcome information and remapping neural geometry to segregate punished from safe actions. Together, these results identify a multiscale neural architecture through which aversive experience can be transformed into flexible behavioral control.