title: Animals lacking link protein have attenuated perineuronal nets and persistent plasticity.
abstract: Chondroitin sulphate proteoglycans in the extracellular matrix restrict plasticity in the adult central nervous system and their digestion with chondroitinase reactivates plasticity. However the structures in the extracellular matrix that restrict plasticity are unknown. There are many changes in the extracellular matrix as critical periods for plasticity close, including changes in chondroitin sulphate proteoglycan core protein levels, changes in glycosaminoglycan sulphation and the appearance of dense chondroitin sulphate proteoglycan-containing perineuronal nets around many neurons. We show that formation of perineuronal nets is triggered by neuronal production of cartilage link protein Crtl1 (Hapln1), which is up-regulated in the visual cortex as perineuronal nets form during development and after dark rearing. Mice lacking Crtl1 have attenuated perineuronal nets, but the overall levels of chondroitin sulphate proteoglycans 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 party denervated cuneate nucleus. The organization of chondroitin sulphate proteoglycan into perineuronal nets is therefore the key event in the control of central nervous system plasticity by the extracellular matrix.
authors.affiliation: Cambridge University Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0PY, UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carulli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pizzorusso
authors.forename: Jessica C F
authors.initials: JC
authors.lastname: Kwok
authors.forename: Elena
authors.initials: E
authors.lastname: Putignano
authors.forename: Andrea
authors.initials: A
authors.lastname: Poli
authors.forename: Serhiy
authors.initials: S
authors.lastname: Forostyak
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Andrews
authors.forename: Sathyaseelan S
authors.initials: SS
authors.lastname: Deepa
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000502:physiology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003624:Darkness; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000502:physiology*; D007839:Functional Laterality; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012683:Sensory Deprivation / Q000502:physiology; D014793:Visual Cortex / Q000254:growth & development / Q000502:physiology; D014796:Visual Perception / Q000502:physiology; D000099249:Proteoglycan Link Protein
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein