Threat intensity shapes cortical engram architecture supporting remote memory retrieval

Abstract

Abstract The strength of persistent threat memories depends on the intensity of an aversive experience. We combined engram tagging with chemogenetics, electrophysiology and spine analyses in male mice to identify how threat intensity, following mild or strong contextual threat conditioning (CTC), shapes physiological and structural properties of prelimbic cortex (PL) pyramidal neurons. PL engram cells selectively mediate retrieval of a mild remote threat memory, and develop neuroadaptations that are time-dependent, dendritic segment-specific, and modulated by threat intensity. Specifically, increased presynaptic release probability, together with reduced postsynaptic strength and spine size, developed regardless of threat intensity. However, addition of long thin spines occurred exclusively on oblique dendrites of engram neurons after mild CTC, aligning with the PL engram contribution to mild, but not strong, threat memory. Our findings reveal how threat intensity shapes cortical engram architecture, which is pivotal for understanding the neural representation of threat memory strength and persistence.