Abstract
Glutamate receptors and ion channels that mediale Ca2+ influx and release play a critical role in the activity-dependenl pruning of immature synaptic circuitry, as shown for N-methyl-D-aspartate (NMDA) receptors in the whisker-related patterning of thalamocortical (TC) synapses and mGluR1 and P/Q-type Ca2+ channels in the elimination of surplus climbing fibers (CFs) onto cerebellar Purkinje cells (PCs). Recently we have identified unique roles played in synapse development by the glutamate transporters GLT1 and GLAST. two astrocytic transporters predominant in the cerebrum and cerebellum, respectively. In the somatosensory cortex of GLT1-knockout mice, whisker-related patterning of TC synapses and their critical period termination occurred normally in the first postnatal week. However, when a lesion was given to row-C whiskers during the critical period (postnatal days 0–3) in GLTl-knockout mice, the shrinkage of lesioned row-C barrels and the reciprocal expansion of intact row-B/D barrels were significantly diminished. Thus, GLT1 magnifies the lesion-induced plasticity of TC synapses during the critical period. In the cerebellum of GLAST-knockout mice. the territorial innervation of PC dendrites, i.e.. the innervation of proximal dendrites by CFs and distal dendrites by parallel fibers, was normally structured. However, dendritic innervation by single major CFs was significantly regressed and. instead, their aberrant wiring to neighboring PC dendrites was induced conspicuously and caused multiple innervation. This aberrant innervation was infrequent during the first 3 postnatal weeks (when surplus CFs are normally eliminated in wild-type rodents), and became progressively exacerbated thereafter. Moreover, in a similar time course, the synapseenwrapping processes of Bergmann glia were progressively retracted, resulting in incomplete glial sealing of PC synapses. Presumably through glutamate uptake and synapse-sealing functions. GLAST thus promotes and maintains CF monoinnervation by consolidating single major CFs innervating the PCs and preventing their aberrant wiring to neighboring PCs. These phenotypes collectively suggest that glutamate transporters operate as an activity discriminator in competitive synaptic wiring; with this operation, major afferents to postsynaptic targets can further expand their innervation, whereas innervation by minor afferents is diminished or suppressed. This molecular function provides neural circuits with a “winner-takes-more” strategy, by which activity-dependent remodeling is facilitated in the developing somatosensory cortex and monoinnervation by single CFs is maintained in the adult cerebellum.
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References
Crepel F (1982) Regression of functional synapses in the immature mammalian cerebellum. Trends Neurosci 5: 266–269
O’Leary DD, Ruff NL, Dyck RH (1994) Development, critical period plasticity, and adult reorganizations of mammalian somatosensory systems. Curr Opin Neurobiol 4: 535–544
Singer W (1995) Development and plasticity of cortical processing architectures. Science 270: 758–764
Crair MC, Malenka RC ( 1995) A critical period for long-term potentiation at thalamocortical synapses. Nature 375: 325–328
Woolsey TA, Van der Loos H (1970) The structural organization of layer IV in the somato-sensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res 17: 205–242
Weller WL, Johnson JI (1975) Barrels in cerebral cortex altered by receptor disruption in newborn, but not in 5-day-old mice (Cricetidoe and Muridae). Brain Res 83: 504–508
Chiaia NL, Bennett-Clarke CA, Rhoades RW (1992) Differential effects of peripheral damage on vibrissa-related patterns in trigeminal nucleus principalis, subnucleus interpolaris, and subnucleus caudalis. Neuroscience 49: 141–156
Yamakado M (1995) Remodelling in the array of cell aggregates in somatotopic representation of the facial vibrissae through the trigeminal sensory system of the mouse. Neurosci Res 23: 399–413
Toki S, Watanabe M, Ichikawa R et al (1999) Early establishment of lesion-insensitive mature barrelettes corresponding to upper lip vibrissae in developing mice. Neurosci Res 33: 9–15
Van der Loos H, Woolsey TA (1973) Somatosensory cortex: structural alterations following early injury to sense organs. Science 179: 395–398
Woolsey TA, Wann JR (1976) Areal changes in mouse cortical barrels following vibrissal damage at different postnatal ages. J Comp Neurol 170: 53–66
Jeanmonod D, Rice FL, Van der Loos H (1977) Mouse somatosensory cortex: Development of the alterations in the barrel field which are caused by injury to the vibrissal follicles. Neurosci Lett 6: 151–156
Li Y, Erzurumlu RS, Chen C, Jhaveri S et al (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76: 427–437
Fox K, Schlaggar BL, Glazewski S et al (1996) Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex. Proc Natl Acad Sci USA 93: 5584–5589
Kutsuwada T, Sakimura K, Manabe T et al (1996) Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor ε2 subunit mutant mice. Neuron 16: 333–344
Iwasato T, Erzurumlu RS, Huerta PT et al (1997) NMDA receptor-dependent refinement of somatotopic maps. Neuron 19: 1201–1210
Iwasato T, Datwani A, Wolf AM et al (2000) Cortex-restricted disruption of NMDA R1 impairs neuronal patterns in the barrel cortex. Nature 406: 726–731
Hannan AJ, Blakemore C, Katsnelson A et al (2001) PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex. Nat Neurosci 4: 282–288
Bravin M, Morando L, Vercelli A et al (1999) Control of spine formation by electrical activity in the adult rat cerebellum. Proc Natl Acad Sci USA 96: 1704–1709
Ichikawa R, Miyazaki T, Kano M et al (2002) Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor GluR™2. J Neurosci 22: 8487–8503
Miyazaki M, Hashimoto K, Shin HS et al (2004) P/Q-type Ca2+ channel α1A regulates synaptic competition on developing cerebellar Purkinje cells. J Neurosci 24: 1734–1743
Watanabe M (2008) Molecular mechanisms governing competitive synaptic wiring in cerebellar Purkinje cells. Tohoku J Exp Med 214: 175–190
Guastavino JM, Sotelo C, Damez-Kinselle I (1990) Hot-foot murine mutation: behavioral effects and neuroanatomical alterations. Brain Res, 523: 199–210
Kashiwabuchi N, Ikeda K, Araki K et al (1995) Impairment of motor coordination Purkinje cell synapse formation and cerebellar long-term depression in GluR™2 mutant mice. Cell 81: 245–252
Kurihara H, Hashimoto K, Kano M et al ( 1997) Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor δ2 subunit (GluR™2). J Neurosci 17: 9613–9623
Hashimoto K, Ichikawa R, Takechi H et al (2001) Roles of glutamate receptor δ2 subunit (GluR™2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development. J Neurosci 21: 9701–9712
Lalouette A, Lohof A, Sotelo C et al (2001 ) Neurobiological effects of a null mutation depend on genetic context: comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor. Neuroscience 105: 443–155
Takeuchi T, Miyazaki T, Watanabe M et al (2005) Control of synaptic connection by glutamate receptor 82 in the mature cerebellum. J Neurosci 25: 2146–2156
Uemura T. Kaldzawa T. Yamasaki M et al (2007) Regulation of long-term depression and climbing fiber territory by GluRδ2 at parallel fiber synapses through its carboxyl terminal domain in cerebellar Purkinje cells. J Neurosci 27: 12 096–12 108
Kakegawa W, Miyazaki T, Emi K et al (2008) Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRδ2. J Neurosci 28: 1460–1468
Kano M, Hashimoto K, Chen C et al (1995) Impaired synapse elimination during cerebellar development in PKCy mutant mice. Cell 83: 1223–1231
Kano M, Hashimoto K, Kurihara H et al (1997) Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1. Neuron 18: 71–79
Kano M, Hashimoto K, Watanabe M et al(1998) Phospholipase C®4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum. Proc Natl Acad Sci USA 95: 15724–15729
Offermanns S, Hashimoto K, Watanabe M et al (1997) Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Gαq. Proc Natl Acad Sci USA 94: 14089–14094
Ichise T, Kano M, Hashimoto K et al (2000) mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination. Science 288: 1832–1835
Hirai H, Pang Z, Bao D et al (2005) Clbn 1 is essential for synaptic integrity and information processing in the cerebellum. Nature Neurosci 8: 1534–1541
Ito-Ishida A, Miura E, Emi K et al (2008) Cbln 1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo. J Neurosci 28: 5920–5930
Hertz L (1979) Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Prog Neurobiol 13: 277–323
Choi DW (1992) Excitotoxic cell death. J Neurobiol 23: 1261–1276
Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65: 1–105
Tanaka K, Watase K, Manabe T et al (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276: 1699–1702
Watase K, Hashimoto K, Kano M et al (1998) Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur J Neurosci 10: 976–988
Katagiri H, Tanaka K, Manabe T (2001) Requirement of appropriate glutamate concentrations in the synaptic cleft for hippocampal LTP induction. Eur J Neurosci 14: 547–553
Voutsinos-Porche B, Bonvento G, Tanaka K et al (2003) Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37: 275–286
Takayasu Y, Iino M, Kakegawa W et al (2005) Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. J Neurosci 25: 8788–8793
Takayasu Y, Iino M, Shimamoto K et al (2006) Glial glutamate transporters maintain one-to-one relationship at the climbing fiber-Purkinje cell synapse by preventing glutamate spillover. J Neurosci 26: 6563–6572
Matsugami TR, Tanemura K, Mieda M et al (2006) Indispensability of the glutamate transporters GLAST and GLT1 to brain development. Proc Natl Acad Sci USA 103: 12 161–12 166
Takasaki C, Okada R, Mitani A et al (2008) Glutamate transporters regulate lesion-induced period plasticity in the developing somatosensory cortex. J Neurosci 28: 4995–5006
Wong-Riley M (1979) Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res 171: 11–28
Finney DJ (1971) Probit analysis, 3rd edn. Cambridge University Press, Cambridge, UK, p 333
Miura E, Fukaya M, Sato T et al (2006) Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain. J Neurochem 97: 1431–1446
Miyazaki T, Fukaya M, Shimizu H et al (2003) Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci 17: 2563–2572
Yamada K, Fukaya M, Shibata T et al (2000) Dynamic transformation of Bergmann glial fibers proceeds in correlation with dendritic outgrowth and synapse formation of cerebellar Purkinje cells. J Comp Neurol 418: 106–120
Kidd FL, Isaac JT (2000) Glutamate transport blockade has a differential effect on AMPA and NMDA receptor-mediated synaptic transmission in the developing barrel cortex. Neuropharmacology 39: 725–732
Demarque M, Villeneuve N, Manent JB et al (2004) Glutamate transporters prevent the generation of seizures in the developing rat neocortex. J Neurosci 24: 3289–3294
Cattani AA, Bonfardin VD, Represa A et al (2007) Generation of slow network oscillations in the developing rat hippocampus after blockade of glutamate uptake. J Neurophysiol 98: 2324–2323
Milh M, Becq H, Villeneuve N et al (2007) Inhibition of glutamate transporters results in a “suppression-burst” pattern and partial seizures in the newborn rat. Epilepsia 48: 169–174
Kano M, Rexhausen U, Dreessen J et al (1992) Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356: 601–604
Konnerth A, Dreessen J Augustine G.J (1992) Brief dendritic calcium signals initiate longlasting synaptic depression in cerebellar Purkinje cells. Proc Natl Acad Sci USA 89: 7051–7055
Regehr WG Mintz IM (1994) Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Neuron 12: 605–613
Lehre KP, Danbolt NC (1998) The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J Neurosci 18: 8751–8757
Takatsuru Y, Takayasu Y, Iino M et al (2006) Roles of glial glutamate transporters in shaping EPSCs at the climbing fiber-Purkinje cell synapses. Neurosci Res 54: 140–148
Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31–39
Aiba A, Kano M, Chen C et al (1994) Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell 79: 377–388
Conquet F, Bashir ZI, Davies CH et al (1994) Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature 372: 237–243
Bear MF (1996) A synaptic basis for memory storage in the cerebral cortex. Proc Natl Acad Sci USA 93: 13453–13459
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Miyazaki, T., Takasaki, C., Watanabe, M. (2010). Neural Circuit Development and Plasticity Shaped by Glutamate Transporters. In: Tamaki, N., Kuge, Y. (eds) Molecular Imaging for Integrated Medical Therapy and Drug Development. Springer, Tokyo. https://doi.org/10.1007/978-4-431-98074-2_22
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DOI: https://doi.org/10.1007/978-4-431-98074-2_22
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