Npas4-mediated dopaminergic regulation of safety memory consolidation

Abstract

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 syn-aptic 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) syn-thesis, which is precluded by stress exposure or corticosterone injection. Herein, we show cellular and mo-lecular mechanisms that regulate the non-threatening (safety) memory consolidation, supporting the fear discrimination.