Npas4-mediated dopaminergic regulation of safety memory consolidation

Amygdala circuitry encodes associations between conditioned stimuli and aversive unconditioned stimuli and also controls fear expression. However, whether and how non-threatening information for unpaired conditioned stimuli (CS^-) is discretely processed remains unknown. The fear expression toward CS^- is robust immediately after fear conditioning but then becomes negligible after memory consolidation. The synaptic plasticity of the neural pathway from the lateral to the anterior basal amygdala gates the fear expression of CS^-, depending upon neuronal PAS domain protein 4 (Npas4)-mediated dopamine receptor D4 (Drd4) synthesis, which is precluded by stress exposure or corticosterone injection. Herein, we show cellular and molecular mechanisms that regulate the non-threatening (safety) memory consolidation, supporting the fear discrimination.