A neuromodulatory circuit-to-molecular pathway for reformatting aversive memories during recall

Memories can be altered when they are recalled through the process of reconsolidation, requiring gene expression in brain cells that store these memories. How brain circuits reformat memories during recall by directing molecular signaling in specific neuronal populations is not known. Here, we show that brainstem noradrenaline projections to the amygdala, a brain region that stores aversive emotional memories, control memory reconsolidation in rats. During reconsolidation, this circuit regulates the nuclear translocation of CREB-regulated transcriptional coactivator-1 (CRTC1), a molecule important for synapse-to-nucleus transcriptional regulation, through β₂-adrenergic receptor (β₂-AR) signaling. Cell-type-specific molecular manipulations revealed that reconsolidation requires both β₂-AR signaling and CRTC1 in an anatomically and genetically defined amygdala cell population. Finally, increasing stress prior to memory recall enhanced reconsolidation, an effect that was mimicked by amygdala cell-type-specific upregulation of noradrenaline signaling. These results reveal a circuit-to-molecular pathway for state-dependent modification of emotional memories during recall.