Npas4-mediated dopaminergic regulation of fear memory states

Abstract

Amygdala circuitry encodes associations between conditioned stimuli and aversive unconditioned stimuli, and also controls fear expression (Pape and Pare, 2010). However, whether and how irrelevant information for unpaired conditioned stimuli (CS-) is discretely processed, and how it was influenced by stress remain unknown. CS- memory is retrievable immediately after fear conditioning, but then becomes silent after memory consolidation in mice. Synaptic pathway from the lateral to the anterior basal amygdala gates the expression of CS- memory, depending upon Npas4-mediated Drd4 synthesis. The upregulation of Npas4-Drd4 axis, which is precluded by corticosterone, shifts functional states of neural engrams for CS- memory toward silent states and limits its retrievability. In here, we demonstrate the cellular and molecular mechanisms regulating the functional states of neural engrams, which can be switched or maintained, supporting discriminative memory.