Top

Published in:

Open Access 01-03-2015 | Original Article

Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury

Authors: C. Orlando, O. Raineteau

Published in: Brain Structure and Function | Issue 2/2015

Abstract

The rapid decline of injury-induced neuronal circuit remodelling after birth is paralleled by the accumulation of chondroitin sulphate proteoglycans (CSPGs) in the extracellular matrix, culminating with the appearance of perineuronal nets (PNNs) around parvalbumin-expressing GABAergic interneurons. We used a spinal cord injury (SCI) model to study the interplay between integrity of PNN CSPGs in the sensorimotor cortex, anatomical remodelling of the corticospinal tract (CST) and motor recovery in adult mice. We showed that thoracic SCI resulted in an atrophy of GABAergic interneurons in the axotomized hindlimb cortex, as well as in a more widespread downregulation of parvalbumin expression. In parallel, spontaneous changes in the integrity of CSPG glycosaminoglycan (GAG) chains associated with PNNs occurred at the boundary between motor forelimb and sensorimotor hindlimb cortex, a region previously showed to undergo reorganization after thoracic SCI. Surprisingly, full digestion of CSPG GAG chains by intracortical chondroitinase ABC injection resulted in an aggravation of motor deficits and reduced sprouting of the axotomized CST above the lesion. Altogether, our data show that changes in the expression pattern of GABAergic markers and PNNs occur in regions of the sensorimotor cortex undergoing spontaneous reorganization after SCI, but suggest that these changes have to be tightly controlled to be of functional benefit.

Available only for authorised users

Aguilar J, Humanes-Valera D, Alonso-Calvino E, Yague JG, Moxon KA, Oliviero A, Foffani G (2010) Spinal cord injury immediately changes the state of the brain. J Neurosci 30(22):7528–7537CrossRefPubMedCentralPubMed

Al-Abdulla NA, Martin LJ (2002) Projection neurons and interneurons in the lateral geniculate nucleus undergo distinct forms of degeneration ranging from retrograde and transsynaptic apoptosis to transient atrophy after cortical ablation in rat. Neuroscience 115(1):7–14CrossRefPubMed

Ayling OG, Harrison TC, Boyd JD, Goroshkov A, Murphy TH (2009) Automated light-based mapping of motor cortex by photoactivation of channelrhodopsin-2 transgenic mice. Nat Methods 6(3):219–224CrossRefPubMed

Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME (2004) The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 7(3):269–277CrossRefPubMed

Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P, McMahon SB, Bradbury EJ (2006) Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 26(42):10856–10867CrossRefPubMedCentralPubMed

Basso DM, Fisher LC, Anderson AJ, Jakeman LB, McTigue DM, Popovich PG (2006) Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J Neurotrauma 23(5):635–659CrossRefPubMed

Benali A, Weiler E, Benali Y, Dinse HR, Eysel UT (2008) Excitation and inhibition jointly regulate cortical reorganization in adult rats. J Neurosci 28(47):12284–12293CrossRefPubMed

Beurdeley M, Spatazza J, Lee HH, Sugiyama S, Bernard C, Di Nardo AA, Hensch TK, Prochiantz A (2012) Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci 32(27):9429–9437CrossRefPubMedCentralPubMed

Bidmon HJ, Jancsik V, Schleicher A, Hagemann G, Witte OW, Woodhams P, Zilles K (1998) Structural alterations and changes in cytoskeletal proteins and proteoglycans after focal cortical ischemia. Neuroscience 82(2):397–420CrossRefPubMed

Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416(6881):636–640CrossRefPubMed

Brown CE, Aminoltejari K, Erb H, Winship IR, Murphy TH (2009) In vivo voltage-sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. J Neurosci 29(6):1719–1734CrossRefPubMed

Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 27(9):2176–2185CrossRefPubMedCentralPubMed

Cafferty WB, Bradbury EJ, Lidierth M, Jones M, Duffy PJ, Pezet S, McMahon SB (2008) Chondroitinase ABC-mediated plasticity of spinal sensory function. J Neurosci 28(46):11998–12009CrossRefPubMedCentralPubMed

Caggiano AO, Zimber MP, Ganguly A, Blight AR, Gruskin EA (2005) Chondroitinase ABCI improves locomotion and bladder function following contusion injury of the rat spinal cord. J Neurotrauma 22(2):226–239CrossRefPubMed

Carter LM, Starkey ML, Akrimi SF, Davies M, McMahon SB, Bradbury EJ (2008) The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury. J Neurosci 28(52):14107–14120CrossRefPubMedCentralPubMed

Carulli D, Pizzorusso T, Kwok JC, Putignano E, Poli A, Forostyak S, Andrews MR, Deepa SS, Glant TT, Fawcett JW (2010) Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain 133(Pt 8):2331–2347CrossRefPubMed

Chau CH, Shum DK, Li H, Pei J, Lui YY, Wirthlin L, Chan YS, Xu XM (2004) Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury. FASEB J 18(1):194–196PubMed

Courtine G, Song B, Roy RR, Zhong H, Herrmann JE, Ao Y, Qi J, Edgerton VR, Sofroniew MV (2008) Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med 14(1):69–74CrossRefPubMedCentralPubMed

de Vivo L, Landi S, Panniello M, Baroncelli L, Chierzi S, Mariotti L, Spolidoro M, Pizzorusso T, Maffei L, Ratto GM (2013) Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex. Nat Commun 4:1484CrossRefPubMed

Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15(5):703–712CrossRefPubMedCentralPubMed

Dityatev A, Bruckner G, Dityateva G, Grosche J, Kleene R, Schachner M (2007) Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets. Dev Neurobiol 67(5):570–588CrossRefPubMed

Fisher D, Xing B, Dill J, Li H, Hoang HH, Zhao Z, Yang XL, Bachoo R, Cannon S, Longo FM, Sheng M, Silver J, Li S (2011) Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. J Neurosci 31(40):14051–14066CrossRefPubMedCentralPubMed

Fouad K, Pedersen V, Schwab ME, Brosamle C (2001) Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses. Curr Biol 11(22):1766–1770CrossRefPubMed

Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD (2005) Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci 25(5):1169–1178CrossRefPubMed

Freund TF, Katona I (2007) Perisomatic inhibition. Neuron 56(1):33–42CrossRefPubMed

Garcia-Alias G, Lin R, Akrimi SF, Story D, Bradbury EJ, Fawcett JW (2008) Therapeutic time window for the application of chondroitinase ABC after spinal cord injury. Exp Neurol 210(2):331–338CrossRefPubMed

Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW (2009) Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 12(9):1145–1151CrossRefPubMed

Ghosh A, Sydekum E, Haiss F, Peduzzi S, Zorner B, Schneider R, Baltes C, Rudin M, Weber B, Schwab ME (2009) Functional and anatomical reorganization of the sensory-motor cortex after incomplete spinal cord injury in adult rats. J Neurosci 29(39):12210–12219CrossRefPubMed

Ghosh A, Haiss F, Sydekum E, Schneider R, Gullo M, Wyss MT, Mueggler T, Baltes C, Rudin M, Weber B, Schwab ME (2010) Rewiring of hindlimb corticospinal neurons after spinal cord injury. Nat Neurosci 13(1):97–104CrossRefPubMed

Ghosh A, Peduzzi S, Snyder M, Schneider R, Starkey M, Schwab ME (2012) Heterogeneous spine loss in layer 5 cortical neurons after spinal cord injury. Cereb Cortex 22(6):1309–1317CrossRefPubMed

Giehl KM, Tetzlaff W (1996) BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo. Eur J Neurosci 8(6):1167–1175CrossRefPubMed

Harauzov A, Spolidoro M, DiCristo G, De Pasquale R, Cancedda L, Pizzorusso T, Viegi A, Berardi N, Maffei L (2010) Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity. J Neurosci 30(1):361–371CrossRefPubMed

Hendry SH, Jones EG (1988) Activity-dependent regulation of GABA expression in the visual cortex of adult monkeys. Neuron 1(8):701–712CrossRefPubMed

Herzog A, Brosamle C (1997) ‘Semifree-floating’ treatment: a simple and fast method to process consecutive sections for immunohistochemistry and neuronal tracing. J Neurosci Methods 72(1):57–63CrossRefPubMed

Hobohm C, Gunther A, Grosche J, Rossner S, Schneider D, Bruckner G (2005) Decomposition and long-lasting downregulation of extracellular matrix in perineuronal nets induced by focal cerebral ischemia in rats. J Neurosci Res 80(4):539–548CrossRefPubMed

Jacobs KM, Donoghue JP (1991) Reshaping the cortical motor map by unmasking latent intracortical connections. Science 251(4996):944–947CrossRefPubMed

Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM (2006) A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci 26(5):1604–1615CrossRefPubMed

Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W (1997) BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 17(24):9583–9595PubMed

Koprivica V, Cho KS, Park JB, Yiu G, Atwal J, Gore B, Kim JA, Lin E, Tessier-Lavigne M, Chen DF, He Z (2005) EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science 310(5745):106–110CrossRefPubMed

Kwok JC, Dick G, Wang D, Fawcett JW (2011) Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol 71(11):1073–1089CrossRefPubMed

Lau CG, Murthy VN (2012) Activity-dependent regulation of inhibition via GAD67. J Neurosci 32(25):8521–8531CrossRefPubMedCentralPubMed

Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B (2000) Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci 20(24):9071–9085PubMed

Lazarus MS, Krishnan K, Huang ZJ (2013) GAD67 Deficiency in parvalbumin interneurons produces deficits in inhibitory transmission and network disinhibition in mouse prefrontal cortex. Cereb Cortex [Epub ahead of print]

Levy LM, Ziemann U, Chen R, Cohen LG (2002) Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation. Ann Neurol 52(6):755–761CrossRefPubMed

Lin R, Kwok JC, Crespo D, Fawcett JW (2008) Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain. J Neurochem 104(2):400–408PubMed

Makara JK, Katona I, Nyiri G, Nemeth B, Ledent C, Watanabe M, de Vente J, Freund TF, Hajos N (2007) Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors. J Neurosci 27(38):10211–10222CrossRefPubMed

Massey JM, Hubscher CH, Wagoner MR, Decker JA, Amps J, Silver J, Onifer SM (2006) Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury. J Neurosci 26(16):4406–4414CrossRefPubMed

McBride RL, Feringa ER, Garver MK, Williams JK Jr (1989) Prelabeled red nucleus and sensorimotor cortex neurons of the rat survive 10 and 20 weeks after spinal cord transection. J Neuropathol Exp Neurol 48(5):568–576CrossRefPubMed

Michaluk P, Wawrzyniak M, Alot P, Szczot M, Wyrembek P, Mercik K, Medvedev N, Wilczek E, De Roo M, Zuschratter W, Muller D, Wilczynski GM, Mozrzymas JW, Stewart MG, Kaczmarek L, Wlodarczyk J (2011) Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology. J Cell Sci 124(Pt 19):3369–3380CrossRefPubMed

Moon LD, Asher RA, Rhodes KE, Fawcett JW (2001) Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 4(5):465–466PubMed

Nielson JL, Sears-Kraxberger I, Strong MK, Wong JK, Willenberg R, Steward O (2010) Unexpected survival of neurons of origin of the pyramidal tract after spinal cord injury. J Neurosci 30(34):11516–11528CrossRefPubMedCentralPubMed

Orlando C, Ster J, Gerber U, Fawcett JW, Raineteau O (2012) Perisynaptic chondroitin sulfate proteoglycans restrict structural plasticity in an integrin-dependent manner. J Neurosci 32(50):18009–18017CrossRefPubMed

Oudega M, Perez MA (2012) Corticospinal reorganization after spinal cord injury. J Physiol 590(Pt 16):3647–3663CrossRefPubMedCentralPubMed

Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L (2002) Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298(5596):1248–1251CrossRefPubMed

Raineteau O, Schwab ME (2001) Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2(4):263–273CrossRefPubMed

Reynolds GP, Abdul-Monim Z, Neill JC, Zhang ZJ (2004) Calcium binding protein markers of GABA deficits in schizophrenia—postmortem studies and animal models. Neurotox Res 6(1):57–61CrossRefPubMed

Sale A, Maya Vetencourt JF, Medini P, Cenni MC, Baroncelli L, De Pasquale R, Maffei L (2007) Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition. Nat Neurosci 10(6):679–681CrossRefPubMed

Salimi I, Friel KM, Martin JH (2008) Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade. J Neurosci 28(29):7426–7434CrossRefPubMedCentralPubMed

Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG (2009) PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326(5952):592–596CrossRefPubMedCentralPubMed

Solodkin A, Veldhuizen SD, Van Hoesen GW (1996) Contingent vulnerability of entorhinal parvalbumin-containing neurons in Alzheimer’s disease. J Neurosci 16(10):3311–3321PubMed

Starkey ML, Bartus K, Barritt AW, Bradbury EJ (2012) Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice. Eur J Neurosci 36(12):3665–3678

Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467(1):60–79CrossRefPubMed

Tang XQ, Wang Y, Huang ZH, Han JS, Wan Y (2004) Adenovirus-mediated delivery of GDNF ameliorates corticospinal neuronal atrophy and motor function deficits in rats with spinal cord injury. NeuroReport 15(3):425–429CrossRefPubMed

Tester NJ, Howland DR (2008) Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats. Exp Neurol 209(2):483–496CrossRefPubMedCentralPubMed

Tetzlaff W, Kobayashi NR, Giehl KM, Tsui BJ, Cassar SL, Bedard AM (1994) Response of rubrospinal and corticospinal neurons to injury and neurotrophins. Prog Brain Res 103:271–286CrossRefPubMed

Tom VJ, Kadakia R, Santi L, Houle JD (2009) Administration of chondroitinase ABC rostral or caudal to a spinal cord injury site promotes anatomical but not functional plasticity. J Neurotrauma 26(12):2323–2333CrossRefPubMedCentralPubMed

van Brederode JF, Helliesen MK, Hendrickson AE (1991) Distribution of the calcium-binding proteins parvalbumin and calbindin-D28k in the sensorimotor cortex of the rat. Neuroscience 44(1):157–171CrossRefPubMed

Wang XB, Bozdagi O, Nikitczuk JS, Zhai ZW, Zhou Q, Huntley GW (2008) Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately. Proc Natl Acad Sci USA 105(49):19520–19525CrossRefPubMedCentralPubMed

Weidner N, Ner A, Salimi N, Tuszynski MH (2001) Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc Natl Acad Sci USA 98(6):3513–3518CrossRefPubMedCentralPubMed

Title: Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury
Authors: C. Orlando
O. Raineteau
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 2/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-013-0701-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2015

The neurobiology of speech perception decline in aging

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

Effects of chronic HIV-1 Tat exposure in the CNS: heightened vulnerability of males versus females to changes in cell numbers, synaptic integrity, and behavior

A quantitative analysis of cellular and synaptic localization of GAT-1 and GAT-3 in rat neocortex

Not all sharks are “swimming noses”: variation in olfactory bulb size in cartilaginous fishes

Differentially disrupted functional connectivity of the subregions of the inferior parietal lobule in Alzheimer’s disease