Figure 4. Failures of extinction conceptualized within an engram framework.

A) Encoding of threat-relevant engram and threat memory extinction in rodents. During extinction, repeated exposure to a CS loses its ability to evoke a conditioned response and weakens the CS engram, generally through context-dependent inhibition. (Notably, Impairment of reconsolidation may directly weaken the CS engram trace). B) Spontaneous recovery can occur when there is a long retention period between extinction and the exposure to a CS resulting in context-independent re-activation of a threat-relevant engram. C) Reinstatement occurs if the US is re-presented without the CS resulting in activation of the previously inhibited threat-relevant engram.