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PLOS ONE  2014 

N-Acetylgalactosamine Positive Perineuronal Nets in the Saccade-Related-Part of the Cerebellar Fastigial Nucleus Do Not Maintain Saccade Gain

DOI: 10.1371/journal.pone.0086154

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Perineuronal nets (PNNs) accumulate around neurons near the end of developmental critical periods. PNNs are structures of the extracellular matrix which surround synaptic contacts and contain chondroitin sulfate proteoglycans. Previous studies suggest that the chondroitin sulfate chains of PNNs inhibit synaptic plasticity and thereby help end critical periods. PNNs surround a high proportion of neurons in the cerebellar nuclei. These PNNs form during approximately the same time that movements achieve normal accuracy. It is possible that PNNs in the cerebellar nuclei inhibit plasticity to maintain the synaptic organization that produces those accurate movements. We tested whether or not PNNs in a saccade-related part of the cerebellar nuclei maintain accurate saccade size by digesting a part of them in an adult monkey performing a task that changes saccade size (long term saccade adaptation). We use the enzyme Chondroitinase ABC to digest the glycosaminoglycan side chains of proteoglycans present in the majority of PNNs. We show that this manipulation does not result in faster, larger, or more persistent adaptation. Our result indicates that intact perineuronal nets around saccade-related neurons in the cerebellar nuclei are not important for maintaining long-term saccade gain.


[1]  Yamaguchi Y (2000) Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci 57 (2) 276–89. doi: 10.1007/pl00000690
[2]  Zimmermann DR, Dours-Zimmermann MT (2008) Extracellular matrix of the central nervous system: from neglect to challenge. Histochem Cell Biol 130 (4) 635–53. doi: 10.1007/s00418-008-0485-9
[3]  Wang D, Fawcett JW (2012) The perineuronal net and the control of CNS plasticity. Cell Tissue Res 349 (1) 147–60. doi: 10.1007/s00441-012-1375-y
[4]  Kwok JC, Afshari F, García-Alías G, Fawcett JW (2008) Proteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC. Restor Neurol Neurosci 26 (2–3) 131–45.
[5]  Morawski M, Brückner G, Arendt T, Matthews RT (2012) Aggrecan: beyond cartilage and into the brain. Int J Biochem Cell Biol 44 (5) 690–3. doi: 10.1016/j.biocel.2012.01.010
[6]  Kwok JC, Warren P, Fawcett JW (2012) Chondroitin sulfate: a key molecule in the brain matrix. Int J Biochem Cell Biol 44 (4) 582–6. doi: 10.1016/j.biocel.2012.01.004
[7]  Silbert JE, Sugumaran G (2002) Biosynthesis of chondroitin/dermatan sulfate. IUBMB Life 54 (4) 177–186. doi: 10.1080/15216540214923
[8]  Hockfield S, Kalb RG, Zaremba S, Fryer H (1990) Expression of neural proteoglycans correlates with the acquisition of mature neuronal properties in the mammalian brain. Cold Spring Harb Symp Quant Biol 55: 505–14. doi: 10.1101/sqb.1990.055.01.049
[9]  Pizzorusso R, Medini P, Berardi N, Chierzi S, Fawcett JW, et al. (2002) Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298 (5596) 1248–51. doi: 10.1126/science.1072699
[10]  McRae PA, Rocco MM, Kelly G, Brumberg JC, Matthews RT (2007) Sensory deprivation alters aggrecan and perineuronal net expression in the mouse barrel cortex. J Neurosci 27 (20) 5405–5413. doi: 10.1523/jneurosci.5425-06.2007
[11]  Hensch TK (2004) Critical period regulation. Annu Rev Neurosci 27: 549–79. doi: 10.1146/annurev.neuro.27.070203.144327
[12]  Bandtlow CE, Zimmerman DR (2000) Proteoglycans in the developing brain: new conceptual insights for old proteins. Phys Rev 80 (4) 1267–90.
[13]  Pizzorusso T, Medini P, Landi S, Baldini S, Berardi N, et al. (2006) Structural and functional recovery from early monocular deprivation in adult rats. Proc Natl Acad Sci U S A 103 (22) 8517–22. doi: 10.1073/pnas.0602657103
[14]  Gogolla N, Caroni P, Lüthi A, Herry C (2009) Perineuronal nets protect fear memories from erasure. Science 325 (5945) 1258–61. doi: 10.1126/science.1174146
[15]  Romberg C, Yang S, Melani R, Andrews MR, Horner AE, et al. (2013) Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex. J Neurosci 33 (16) 7057–65. doi: 10.1523/jneurosci.6267-11.2013
[16]  Foscarin S, Ponchione D, Pajaj E, Leto K, Gawlak M, et al. (2011) Experience-dependent plasticity and modulation of growth regulatory molecules at central synapses. PLoS One 6 (1) e16666. doi: 10.1371/journal.pone.0016666
[17]  Carulli D, Rhodes KE, Brown DJ, Bonnert TP, Pollack SJ, et al. (2006) Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components. J Comp Neurol 494 (4) 559–77. doi: 10.1002/cne.20822
[18]  J?ger C, Lendvai D, Seeger G, Brückner G, Matthews RT, et al. (2013) Perineuronal and perisynaptic extracellular matrix in the human spinal cord. Neuroscience 238: 168–184. doi: 10.1016/j.neuroscience.2013.02.014
[19]  Ghez C, Thach WT (2000) The cerebellum. In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science, 4th edition. New York: McGraw-Hill, pp. 831–352.
[20]  Crook J, Hendrickson A, Erickson A, Possin D, Robinson F (2007) Purkinje cell axon collaterals terminate on Cat-301+ neurons in macaca monkey cerebellum. Neuroscience 149: 834–844. doi: 10.1016/j.neuroscience.2007.08.030
[21]  Noda H, Murakami S, Yamada J, Tamada J, Tamaki Y, et al. (1988) Saccadic eye movements evoked by microstimulation of the fastigial nucleus of macaque monkeys. J Neurophysiol 60 (3) 1036–52.
[22]  Ohtsuka K, Noda H (1990) Direction-selective saccadic-burst neurons in the fastigial oculomotor region of the macaque. Exp Brain Res 81 (3) 659–62. doi: 10.1007/bf02423517
[23]  Fuchs AF, Robinson FR, Straube A (1993) Role of the caudal fastigial nucleus in saccade generation. I. Neuronal discharge pattern. J Neurophysiol 70 (5) 1723–40.
[24]  Robinson FR, Straube A, Fuchs AF (1993) Role of the caudal fastigial nucleus in saccade generation. II. Effects of muscimol inactivation. J Neurophysiol 70 (5) 1741–58.
[25]  Goffart L, Chen LL, Sparks DL (2004) Deficits in saccades and fixation during muscimol inactivation of the caudal fastigial nucleus in the rhesus monkey. J Neurophysiol 92 (6) 3351–67. doi: 10.1152/jn.01199.2003
[26]  Goldberg ME, Musil SY, Fitzgibbon EJ, Smith M, Olson CR (1993). The role of the cerebellum in the control of saccadic eye movements. In: Mano N, Hamada I, DeLong MR, editors. Role of the cerebellum and basal ganglia in voluntary movement. Amsterdam: Elesvier, pp. 203–2011.
[27]  Brückner G, Bringmann A, H?rtig W, K?ppe G, Delpech B, et al. (1998) Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain. Exp Brain Res 121: 300–310. doi: 10.1007/s002210050463
[28]  Matthews RT, Kelly GM, Zerillo CA, Gray G, Tiemeyer M, et al. (2002) Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets. J Neurosci 22 (17) 7536–47.
[29]  Schmalfeldt M, Dours-Zimmermann MT, Winterhalter KH, Zimmermann DR (1998) Versican V2 is a major extracellular matrix component of the mature bovine brain. J Biol Chem 273: 15758–15764. doi: 10.1074/jbc.273.25.15758
[30]  Oike Y, Kimayta K, Shimomura T, Nakazawa K, Suzuki S (1980) Structural analysis of chick-embryo cartilage proteoglycan by selective degradation of chondroitin lyases (chondroitinases) and endo-b-D-galactosidase (keratanase). Biochem J 191: 193–207.
[31]  Robinson FR, Soetedjo R, Noto C (2006) Distinct short-term and long-term adaptation to reduce saccade size in monkey. J Neurophysiol 96 (3) 1030–41. doi: 10.1152/jn.01151.2005
[32]  Mueller AL, Davis AJ, Robinson FR (2012) Long-term size-increasing adaptation of saccades in macaques. Neuroscience 224: 38–47. doi: 10.1016/j.neuroscience.2012.08.012
[33]  Fuchs AF, Robinson DA (1966) A method for measuring horizontal and vertical eye movement chronically in the monkey. J Appl Physiol 21 (3) 1068–70.
[34]  Judge SJ, Richmond BJ, Chu FC (1980) Implantation of magnetic search coils for measurement of eye position: an improved method. Vision Res 20 (6) 535–8. doi: 10.1016/0042-6989(80)90128-5
[35]  McLaughlin SG (1967) Parametric adjustment in saccadic eye movements. Percept Psychophys 2: 359–362. doi: 10.3758/bf03210071
[36]  Straube A, Fuchs AF, Usher S, Robinson FR (1997) Characteristics of saccadic gain adaptation in rhesus macaques. J Neurophysiol 77 (2) 874–95.
[37]  Seeberger T, Noto C, Robinson F (2002) Non-visual information does not drive saccade gain adaptation in monkeys. Brain Res 956 (2) 374–9. doi: 10.1016/s0006-8993(02)03577-1
[38]  Schuirmann DJ (1987) A comparison of the two onesided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokin Biopharm 15: 657–680. doi: 10.1007/bf01068419
[39]  Carlson SS, Iwata M, Wight TN (1996) A chondroitin sulfate/keratan sulfate proteoglycan, PG-1000, forms complex with are concentrated in the reticular laminae of electric organ basement membranes. Matrix Biol 15: 281–92. doi: 10.1016/s0945-053x(96)90118-3
[40]  Schnell SA, Staines WA, Wessendorf MW (1999) Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem 47 (6) 719–730. doi: 10.1177/002215549904700601
[41]  McKay BE, Molineux ML, Turner RW (2004) Biotin is endogenously expressed in select regions of the rat central nervous system. J Comp Neurol 473 (1) 86–96. doi: 10.1002/cne.20109
[42]  Goffart L, Chen LL, Sparks DL (2004) Deficits in saccades and fixation during muscimol inactivation of the caudal fastigial nucleus in the rhesus monkey. J Neurophysiol 92 (6) 3351–67. doi: 10.1152/jn.01199.2003
[43]  Buzunov E, Mueller A, Straube A, Robinson FR (2013) When during horizontal saccades in moke does cerebellar output affect movement? Brain Res 1503: 33–42. doi: 10.1016/j.brainres.2013.02.001
[44]  H?rtig W, Derouiche A, Welt K, Brauer K, Grosche J, et al. (1999) Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations. Brain Res 842: 15–29. doi: 10.1016/s0006-8993(99)01784-9
[45]  Horn AK, Brückner G, H?rtig W, Messoudi A (2002) Saccadic omnipause and burst neurons in monkey and human are ensheathed by perineuronal nets but differ in their expression of calcium-binding proteins. J Comp Neurol 445 (3) 341–352. doi: 10.1002/cne.10495
[46]  Rhodes KE, Fawcett JW (2004) Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? J Anat 204: 33–48. doi: 10.1111/j.1469-7580.2004.00261.x
[47]  Inaba N, Iwamoto Y, Yoshida K (2003) Changes in cerebellar fastigial burst activity related to saccade gain adaptation in the monkey. Neurosci Res 46 (3) 359–68. doi: 10.1016/s0168-0102(03)00098-1
[48]  Sale A, Vetencourt JFM, Medini P, Cenni MC, Baroncelli L, et al. (2007) Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition. Nat Neurosci 10: 679–81. doi: 10.1038/nn1899
[49]  Deák á, Bácskai T, Gaál B, Rácz é, Matesz K (2012) Effect of unilateral labyrinthectomy on the molecular composition of perineuronal nets in the lateral vestibular nucleus of the rat. Neurosci Lett 513 (1) 1–5. doi: 10.1016/j.neulet.2012.01.076
[50]  Carulli D, Pizzorusso T, Kwok JC, Putignano E, Poli A, et al. (2010) Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain 133 (8) 2331–47. doi: 10.1093/brain/awq145
[51]  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. Nature Neurosci 4: 465–466.
[52]  Corvetti L, Rossi F (2005) Degradation of chondroitin sulfate proteoglycans induces sprouting of intact Purkinje axons in the cerebellum of the adult rat. J Neurosci 25 (31) 7150–7158. doi: 10.1523/jneurosci.0683-05.2005
[53]  Dityatev A, Brückner G, Diyateva G, Grosche J, Kleene R, et al. (2007) Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets. Dev Neurobiol 67 (5 570–88. doi: 10.1002/dneu.20361


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