Indeed, the nature of the renewal deficits in young rats is similar to that in adult rats with hippocampal lesions (Corcoran et al., 2005, Corcoran and Maren, 2001, Corcoran and Maren, 2004, Hobin et al., 2006, Ji and Maren, 2005 and Ji and Maren, 2008a): both young rats and adult

rats with hippocampal lesions fail to renew fear to an extinguished CS outside of the extinction context. Hence, the development of the hippocampus may afford a flexible memory system that allows a CS to mean different things in different contexts. This explanation of how extinction comes to be resistant to erasure emphasizes the development of neural systems that allow the flexible representation of information. GSK1210151A cell line Another possibility is that the synaptic network that encodes fear memory is fundamentally different in young animals. In fact, Gogolla and colleagues have recently observed

in mice that the development of the amygdala extracellular matrix, in particular perineuronal nets composed of chondroitin sulfated proteoglycans (CSPGs), parallels the development of extinction learning (Gogolla et al., 2009). Interestingly, infusion of a CSPG-degrading enzyme (chondroitinase ABC or chABC) into the amygdala of an adult mouse digested perineuronal nets and produced a fear extinction phenotype like that of a young mouse. That is, chABC-treated mice exhibited normal conditioning and consolidation of fear conditioning, and

Ku-0059436 manufacturer also showed normal decreases in conditioned fear after extinction training. Remarkably, however, chABC-treated rats did not show spontaneous recovery or renewal of fear. This suggests that perineuronal nets, while not necessary for the acquisition of fear memory, may prevent those memories for PAK6 destabilizing after extinction training. The mechanism by which degradation of perineuronal nets alters the stability of fear memory is not known, although chABC impairs several forms of synaptic plasticity in the amygdala and hippocampus. Independent of the precise mechanism, however, these data suggest that molecular factors at the synapse are not only involved in the long-term maintenance of memory, but in protecting those memories from the destabilizing influences of other behavioral experiences. Unfortunately, though, removing perineuronal nets in the amygdala only promotes a non-recoverable extinction of fear when chABC is applied before, but not after fear conditioning. This obviously limits the therapeutic potential of compounds targeting perineuronal nets insofar as they would have to be administered before a traumatic experience and would presumably be ineffective at promoting the suppression of old fears.