Threat intensity shapes cortical engram architecture supporting remote memory retrieval

The strength of persistent threat memories depends on the intensity of an aversive experience. We combined engram tagging with chemogenetics, electrophysiology and structural spine analyses to identify how threat intensity, following mild or strong contextual threat conditioning (CTC), shapes maturation of prelimbic cortex (PL) pyramidal engram neurons. PL engram cells mediate retrieval of mild, but not strong, remote threat memories, and develop neuroadaptations that are time-dependent, dendritic segment-specific, and modulated by threat intensity. Specifically, mild CTC increased synaptic connectivity by addition of long thin spines on oblique dendrites of engram neurons. Increased presynaptic release probability, together with reduced postsynaptic strength and spine size, developed regardless of threat intensity. Excitability was reduced in strong CTC-activated PL neurons without an increase in synaptic connectivity, supporting their functional disengagement. Our findings reveal how threat intensity shapes cortical engram architecture, which is pivotal for understanding the neural representation of threat memory strength and persistence.