ANIMALS LACKING LINK PROTEIN HAVE ATTENUATED PERINEURONAL NETS AND PERSISTENT PLASTICITY

Chondroitin sulphate proteoglycans (CSPGs) in the extracellular matrix (ECM) restrict plasticity in the adult CNS, and their digestion with chondroitinase reactivates plasticity. However the structures in the ECM that restrict plasticity are unknown. There are many changes in the ECM as critical periods for plasticity close, including changes in CSPG core protein levels, changes in glycosaminoglycan sulphation and the appearance of dense CSPG-containing perineuronal nets (PNNs) around many neurons. We show that formation of PNNs is triggered by neuronal production of cartilage link protein Crtl1 (Hapln1), which is upregulated in the visual cortex as PNNs form during development and after dark rearing. Mice lacking Crtl1 have attenuated perineuronal nets, but the overall levels of CSPGs and their pattern of glycan sulphation are unchanged. Crtl1 knockout animals retain juvenile levels of ocular dominance plasticity and their visual acuity remains sensitive to visual deprivation. In the sensory pathway, axons in knockout animals but not controls sprout into the partly denervated cuneate nucleus. The organization of CSPGs into perineuronal nets is therefore the key event in the control of CNS plasticity by the ECM.