Chondroitin sulphate proteoglycans (CSPG) are chondroitin sulfate polysaccharides that attach to the hydroxyl groups of serine residues on proteins. The negative charges on the chondroitin sulfate are important for regulating the brain’s perineuronal nets, mostly prominently via the inhibition of the sprouting and growth of axons. One region where it has been shown to regulate plasticity is in the visual cortex, which normally has plasticity during an early critical period of development which is lost in adults. When Pizzorusso et al degraded the CSPG glycosaminoglycan (GAG) chains of live adult rats using chondroitinase-ABC, it shifted the ocular dominance towards the non-deprived eye, an indicator of plasticity. The authors suggest that removing the inhibitory CSPG GAG chains may have restored experience-dependent generation of synaptic connections and/or their rearrangement.
Now Gogolla et al have shown that a similar mechanism of plasticity exists in the amygdala for CS-US conditioned fear response memories. These memories can be extinguished via CS presentations with the US in juvenile (i.e., post-natal day 16) rats, but this is not normally possible in adult rats, which exhibit spontaneous recovery of the CS-US fear response despite extinction. In an attempt to convert the adult phenotype to the juvenile phenotype, the researchers injected chondroitinase ABC into the basolateral amygdala of 3-month old rats in order to destroy their extracellular perineuronal nets. After fear conditioning, these enzyme injected adult rats were identical to controls, as indicated by the levels of freezing in response to the CS. And after extinction training, both condroitinase ABC injected and control rats exhibited the same depression of freezing responses. But when the rats were retested at 7 or 28 days post-extinction, the adult condrotinase ABC injected rats did not exhibit spontaneous recovery of the fear response, thus restoring the juvenile phenotype, while the control rats did exhibit spontaneous recovery. Since juveniles rats also do not have well developed perineuronal nets, it appears that these extracellular nets prevent the unlearning of a conditioned fear response and thus impede plasticity in the amygdala.
The fact that perineuronal nets regulated by CSPG are responsible for mediating the development shift away from plasticity with age in both the visual cortex and the amygdala indicates that it may have a role for information storage changes in neuronal circuits in general. The synapse is the key circuit element of the human brain and the ability to manipulate its plasticity would be a major breakthrough towards neural engineering.
References
Pizzorusso T et al. 2002 Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298:1248-1251. doi: 10.1126/science.1072699.
Gogolla N et al. 2009 Perineuronal nets protect fear memories from erasure. Science 325:1258 – 1261. doi: 10.1126/science.1174146.
