Structural, Synaptic, and Epigenetic Dynamics of Enduring Memories

Box 1

Recent insights into structural plasticity and remote fear memory extinction.

In addition to remote memory storage, memory extinction—in the case of remote fearful memories—also alters structural spine

plasticity. For instance, remote memory extinction was found to diversely alter the spine density and spine size in the ACC and

infralimbic cortex (ILC) in mice [78]: extinction of a 31-day-old contextual fear memory decreased the density of dendritic spines

in the ACC significantly, but not the size. In contrast, the spine density remained elevated in the ILC but the size of spines decreased

dramatically. The persistence of spine enlargement in the ACC upon extinction could be essential to warrant that the consolidated

fear and the extinction memory traces are kept in a dormant state to allow their reactivation long after training. This may indicate

that the extinction per se partially remodels the neuronal network supporting the original memory representation. Intriguingly,

another study described the opposite effects of fear conditioning and extinction on dendritic spine remodeling in the frontal

association cortex (FrA) of rats [79]. Using two-photon microscopy to examine the formation and elimination of postsynaptic

dendritic spines of the FrA, the cued fear conditioning caused rapid and long-lasting spine elimination that was significant over 2

and 9 days. After 2 days of extinction training, the spine formation was significantly increased and its degree predicted the

effectiveness of the extinction to reduce the conditioned freezing response. These results paradoxically conclude that fear

conditioning mainly promotes spine elimination, whereas extinction essentially induces spine formation. More studies in different

brain areas will be of high interest to corroborate these findings.