Gogolla et al. present evidence that fear memories are protected from erasure (extinction) by an matrix of compounds (chondroitin sulfate proteoglycans) outside of nerve cells in the amygdala, ie. in the extra-cellular matrix:
In adult animals, fear conditioning induces a permanent memory that is resilient to erasure by extinction. In contrast, during early postnatal development, extinction of conditioned fear leads to memory erasure, suggesting that fear memories are actively protected in adults. We show here that this protection is conferred by extracellular matrix chondroitin sulfate proteoglycans (CSPGs) in the amygdala. The organization of CSPGs into perineuronal nets (PNNs) coincided with the developmental switch in fear memory resilience. In adults, degradation of PNNs by chondroitinase ABC specifically rendered subsequently acquired fear memories susceptible to erasure. This result indicates that intact PNNs mediate the formation of erasure-resistant fear memories and identifies a molecular mechanism closing a postnatal critical period during which traumatic memories can be erased by extinction.These results, together with previous experiments in the visual cortex on visual plasticity, suggest that maturation of the extracellular matrix could be a mechanism used by different brain circuits to change from a malleable to a more crystallized state during development. The presence of a high concentration of CSPGs in the perineuronal nets surrounding inhibitory neurons suggests that inhibitory circuits could play an important role in the developmental control of plasticity.