Engram activation reinstates the susceptibility of consolidated memory traces to retrograde amnesia by functional blockade of parabrachial nuclei.

Previous studies have shown that in rats the acquisition of a step-through passive avoidance reaction (PAR) in the light-dark box apparatus is disrupted by tetrodotoxin (TTX) inactivation of the parabrachial nuclei (PBN) 24 but not 48 h after the acquisition trial. The present experiment shows that TTX induces retrograde amnesia even when applied to the PBN 48 h after PAR acquisition only if it is preceded by a 30-min confinement (extinction) or by a footshock (retraining) in the dark compartment. These stimuli, independently of their sign, induce quantitatively comparable TTX disrupting effects. This happens notwithstanding the fact that these stimuli are too weak to modify PAR under control conditions. This paradoxical finding suggests that engram vulnerability may not be a simple inverse function of its recency but that it may reflect a reactivation of the neural circuits involved in memory trace formation. Consolidated engrams become again vulnerable only when contextual cue stimuli are presented shortly before the application of the disrupting procedure.