Associative coding of conditioned fear in the thalamic nucleus reuniens in rodents and humans

Abstract

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remains unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. In rats, we additionally found that spontaneous neural activity in RE tracks defensive freezing and shows anticipatory increases in calcium activity that precede the termination of freezing behavior. Single-unit recordings in rats confirmed that individual RE neurons index both the associative value of the CS and defensive behavior transitions. Moreover, distinct neuronal ensembles in the RE encode fear versus extinction memories. These findings suggest a conserved role of the RE across species in modulating defensive states and emotional memory processes, providing a foundation for future translational research on fear-related disorders.