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Birth, growth and elimination of a single synapse

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Abstract

Synapses are functional units regulating information flows in the neuronal circuits. How synaptic junctions are formed and remodelled is a fundamental question in developmental neurobiology. In recent years, it has become possible to visualize the formation, maintenance and remodelling of a single synapse by using new imaging methods. These studies, identifying synaptic structures by lipophilic dye markers and genetically modified synaptic molecules with fluorescent proteins, provided new insights into synapse development and maturation. Experimental evidence indicates very rapid assembly of both presynaptic and postsynaptic marker proteins at newly formed synaptic junctions. Morphological expansion of the synaptic junctional membrane is tightly coupled to both efficacy of the presynaptic neurotransmitter release and postsynaptic receptor distribution. The elimination process of pre-existing synapses has also been reported, and evidence for persistent remodelling of synaptic junctions has been provided. Information regarding birth, maturation and elimination of a single synapse is accumulating and will influence our concepts about how neuronal circuits are organized and maintained.

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References

  • Adams CL, Chen YT, Smith SJ, Nelson WJ (1998) Mechanisms of epithelial cell-cell adhesion and cell compaction revealed by high-resolution tracking of E-cadherin-green fluorescent protein. J Cell Biol 142, 1105–19.

    Article  PubMed  CAS  Google Scholar 

  • Ahmari SE, Buchanan J, Smith SJ (2000) Assembly of presynaptic active zones from cytoplasmic transport packets. Nat Neurosci 3, 445–51.

    Article  PubMed  CAS  Google Scholar 

  • Bozdagi O, Shan W, Tanaka H, Benson DL, Huntley GW (2000) Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation. Neuron 28, 245–59.

    Article  PubMed  CAS  Google Scholar 

  • Bresler T, Ramati Y, Zamorano PL, Zhai R, Garner CC, Ziv NE (2001) The dynamics of SAP90/PSD-95 recruitment to new synaptic junctions. Mol Cell Neurosci 18, 149–67.

    Article  PubMed  CAS  Google Scholar 

  • Cho KO, Hunt CA, Kennedy MB (1992) The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9, 929–42.

    Article  PubMed  CAS  Google Scholar 

  • Cochilla AJ, Angleson JK, Betz WJ (1999) Monitoring secretory membrane with FM1-43 fluorescence. Ann Rev Neurosci 22, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Dahm LM, Landmesser LT (1991) The regulation of synaptogenesis during normal development and following activity blockade. J Neurosci 11, 238–55.

    PubMed  CAS  Google Scholar 

  • Dailey ME, Smith SJ (1996) The dynamics of dendritic structure in developing hippocampal slices. J Neurosci 16, 2983–94.

    PubMed  CAS  Google Scholar 

  • Dalva MB, Takasu MA, Lin MZ et al. (2000) EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103, 945–56.

    Article  PubMed  CAS  Google Scholar 

  • Dunaevsky A, Tashiro A, Majewska A, Mason C, Yuste R (1999) Developmental regulation of spine motility in the mammalian central nervous system. Proc Natl Acad Sci USA 96, 13438–43.

    Article  PubMed  CAS  Google Scholar 

  • Durand GM, Kovalchuk Y, Konnerth A (1996) Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–5.

    Article  PubMed  CAS  Google Scholar 

  • Eccles JC, Llinas R, Sasaki K (1966) The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum. J Physiol 182, 268–96.

    PubMed  CAS  Google Scholar 

  • El-Husseini Ael D, Schnell E, Dakoji S et al. (2002) Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108, 849–63.

    Article  Google Scholar 

  • El-Husseini AE, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290, 1364–8.

    PubMed  CAS  Google Scholar 

  • Ethell IM, Irie F, Kalo MS, Couchman JR, Pasquale EB, Yamaguchi Y (2001) EphB/syndecan-2 signaling in dendritic spine morphogenesis. Neuron 31, 1001–13.

    Article  PubMed  CAS  Google Scholar 

  • Ethell IM, Yamaguchi Y (1999) Cell surface heparan sulfate proteoglycan syndecan-2 induces the maturation of dendritic spines in rat hippocampal neurons. J Cell Biol 144, 575–86.

    Article  PubMed  CAS  Google Scholar 

  • Fannon AM, Colman DR (1996) A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17, 423–34.

    Article  PubMed  CAS  Google Scholar 

  • Fiala JC, Feinberg M, Popov V, Harris KM (1998) Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J Neurosci 18, 8900–11.

    PubMed  CAS  Google Scholar 

  • Flanagan JG, Vanderhaeghen P (1998) The ephrins and Eph receptors in neural development. Ann Rev Neurosci 21, 309–45.

    Article  PubMed  CAS  Google Scholar 

  • Friedman HV, Bresler T, Garner CC, Ziv NE (2000) Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment. Neuron 27, 57–69.

    Article  PubMed  CAS  Google Scholar 

  • Gale NW, Yancopoulos GD (1997) Ephrins and their receptors: a repulsive topic? Cell Tiss Res 290, 227–41.

    Article  CAS  Google Scholar 

  • Gould E, Woolley CS, Frankfurt M, McEwen BS (1990) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 10, 1286–91.

    PubMed  CAS  Google Scholar 

  • Grunwald IC, Korte M, Wolfer D et al. (2001) Kinase-Independent Requirement of EphB2 Receptors in Hippocampal Synaptic Plasticity. Neuron 32, 1027–40.

    Article  PubMed  CAS  Google Scholar 

  • Harris KM, Jensen FE, Tsao B (1992) Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. J Neurosci 12, 2685–705.

    PubMed  CAS  Google Scholar 

  • Hayashi K, Shirao T (1999) Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons. J Neurosci 19, 3918–25.

    PubMed  CAS  Google Scholar 

  • Hebb DO (1949) The Organization of Behavior. Wiley, New York.

    Google Scholar 

  • Henderson JT, Georgiou J, Jia Z et al. (2001) The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron 32, 1041–56.

    Article  PubMed  CAS  Google Scholar 

  • Hensch TK, Fagiolini M, Mataga N, Stryker MP, Baekkeskov S, Kash SF (1998) Local GABA circuit control of experiencedependent plasticity in developing visual cortex. Science 282, 1504–8.

    Article  PubMed  CAS  Google Scholar 

  • Hubel DH, Wiesel TN, LeVay S (1977) Plasticity of ocular dominance columns in monkey striate cortex. Phil Trans R Soc London Biol Sci 278, 377–409.

    Article  CAS  Google Scholar 

  • Hume RI, Role LW, Fischbach GD (1983) Acetylcholine release from growth cones detected with patches of acetylcholine receptor-rich membranes. Nature 305, 632–4.

    Article  PubMed  CAS  Google Scholar 

  • Ichtchenko K, Hata Y, Nguyen T et al. (1995) Neuroligin 1: a splice site-specific ligand for beta-neurexins. Cell 81, 435–43.

    Article  PubMed  CAS  Google Scholar 

  • Iino R, Koyama I, Kusumi A (2001) Single molecule imaging of green fluorescent proteins in living cells: E-cadherin forms oligomers on the free cell surface. Biophys J 80, 2667–77.

    Article  PubMed  CAS  Google Scholar 

  • Irie M, Hata Y, Takeuchi M et al. (1997) Binding of neuroligins to PSD-95. Science 277, 1511–5.

    Article  PubMed  CAS  Google Scholar 

  • Isaac JT, Nicoll RA, Malenka RC (1995) Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427–34.

    Article  PubMed  CAS  Google Scholar 

  • Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269, 1737–40.

    Article  PubMed  CAS  Google Scholar 

  • Lendvai B, Stern EA, Chen B, Svoboda K (2000) Experiencedependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–81.

    Article  PubMed  CAS  Google Scholar 

  • Liao D, Zhang X, O’Brien R, Ehlers MD, Huganir RL (1999) Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat Neurosci 2, 37–43.

    Article  PubMed  CAS  Google Scholar 

  • Mariani J, Changeux JP (1981) Ontogenesis of olivocerebellar relationships. I. Studies by intracellular recordings of the multiple innervation of Purkinje cells by climbing fibers in the developing rat cerebellum. J Neurosci 1, 696–702.

    PubMed  CAS  Google Scholar 

  • Marrs GS, Green SH, Dailey ME (2001) Rapid formation and remodeling of postsynaptic densities in developing dendrites. Nat Neurosci 4, 1006–13.

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4, 1086–92.

    Article  PubMed  CAS  Google Scholar 

  • Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309, 261–3.

    Article  PubMed  CAS  Google Scholar 

  • Migaud M, Charlesworth P, Dempster M et al. (1998) Enhanced longterm potentiation and impaired learning in mice with mutant postsynaptic density-95 protein [see comments]. Nature 396, 433–9.

    Article  PubMed  CAS  Google Scholar 

  • Murphy DD, Segal M (1996) Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones. J Neurosci 16, 4059–68.

    PubMed  CAS  Google Scholar 

  • Murthy VN, Schikorski T, Stevens CF, Zhu Y (2001) Inactivity produces increases in neurotransmitter release and synapse size. Neuron 32, 673–82.

    Article  PubMed  CAS  Google Scholar 

  • Murthy VN, Sejnowski TJ, Stevens CF (1997) Heterogeneous release properties of visualized individual hippocampal synapses. Neuron 18, 599–612.

    Article  PubMed  CAS  Google Scholar 

  • Naisbitt S, Kim E, Tu JC et al. (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23, 569–82.

    Article  PubMed  CAS  Google Scholar 

  • Nusser Z, Lujan R, Laube G, Roberts JD, Molnar E, Somogyi P (1998) Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–59.

    Article  PubMed  CAS  Google Scholar 

  • O’Brien RJ, Kamboj S, Ehlers MD, Rosen KR, Fischbach GD, Huganir RL (1998) Activity-dependent modulation of synaptic AMPA receptor accumulation. Neuron 21, 1067–78.

    Article  PubMed  CAS  Google Scholar 

  • O’Brien RJ, Xu D, Petralia RS, Steward O, Huganir RL, Worley P (1999) Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23, 309–23.

    Article  PubMed  CAS  Google Scholar 

  • Okabe S, Kim HD, Miwa A, Kuriu T, Okado H (1999) Continual remodeling of postsynaptic density and its regulation by synaptic activity. Nat Neurosci 2, 804–11.

    Article  PubMed  CAS  Google Scholar 

  • Okabe S, Miwa A, Okado H (2001) Spine formation and correlated assembly of presynaptic and postsynaptic molecules. J Neurosci 21, 6105–14.

    PubMed  CAS  Google Scholar 

  • Pak DT, Yang S, Rudolph-Correia S, Kim E, Sheng M (2001) Regulation of dendritic spine morphology by SPAR, a PSD- 95-associated RapGAP. Neuron 31, 289–303.

    Article  PubMed  CAS  Google Scholar 

  • Penzes P, Johnson RC, Sattler R et al. (2001) The neuronal Rho- GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron 29, 229–42.

    Article  PubMed  CAS  Google Scholar 

  • Petralia RS, Esteban JA, Wang YX et al. (1999) Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat Neurosci 2, 31–6.

    Article  PubMed  CAS  Google Scholar 

  • Phillips GR, Huang JK, Wang Y et al. (2001) The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution. Neuron 32, 63–77.

    Article  PubMed  CAS  Google Scholar 

  • Philpot BD, Sekhar AK, Shouval HZ, Bear MF (2001) Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex. Neuron 29, 157–69.

    Article  PubMed  CAS  Google Scholar 

  • van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415, 1030–4.

    Article  PubMed  CAS  Google Scholar 

  • Prange O, Murphy TH (2001) Modular transport of postsynaptic density-95 clusters and association with stable spine precursors during early development of cortical neurons. J Neurosci 21, 9325–33.

    PubMed  CAS  Google Scholar 

  • Rajfur Z, Roy P, Otey C, Romer L, Jacobson K (2002) Dissecting the link between stress fibres and focal adhesions by CALI with EGFP fusion proteins. Nat Cell Biol 4, 286–93.

    Article  PubMed  CAS  Google Scholar 

  • Rao A, Craig AM (1997) Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron 19, 801–12.

    Article  PubMed  CAS  Google Scholar 

  • Sala C, Piech V, Wilson NR, Passafaro M, Liu G, Sheng M (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31, 115–30.

    Article  PubMed  CAS  Google Scholar 

  • Scheiffele P, Fan J, Choih J, Fetter R, Serafini T (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–69.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz IR, Pappas GD, Purpura DP (1968) Fine structure of neurons and synapses in the feline hippocampus during postnatal ontogenesis. Exp Neurol 22, 394–407.

    Article  PubMed  CAS  Google Scholar 

  • Setou M, Nakagawa T, Seog DH, Hirokawa N (2000) Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288, 1796–802.

    Article  PubMed  CAS  Google Scholar 

  • Setou M, Seog DH, Tanaka Y et al. (2002) Glutamate-receptorinteracting protein GRIP1 directly steers kinesin to dendrites. Nature 417, 83–7.

    Article  PubMed  CAS  Google Scholar 

  • Shirao T (1995) The roles of microfilament-associated proteins, drebrins, in brain morphogenesis: a review. J Biochem 117, 231–6.

    Article  PubMed  CAS  Google Scholar 

  • Song JY, Ichtchenko K, Sudhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96, 1100–5.

    Article  PubMed  CAS  Google Scholar 

  • Takumi Y, Ramirez-Leon V, Laake P, Rinvik E, Ottersen OP (1999) Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2, 618–24.

    Article  PubMed  CAS  Google Scholar 

  • Torres R, Firestein BL, Dong H et al. (1998) PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron 21, 1453–63.

    Article  PubMed  CAS  Google Scholar 

  • Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–6.

    Article  PubMed  CAS  Google Scholar 

  • Uchida N, Honjo Y, Johnson KR, Wheelock MJ, Takeichi M (1996) The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol 135, 767–79.

    Article  PubMed  CAS  Google Scholar 

  • Woolley CS, Gould E, Frankfurt M, McEwen BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10, 4035–9.

    PubMed  CAS  Google Scholar 

  • Woolley CS, McEwen BS (1992) Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat [published erratum appears in 1992 J Neurosci 12. J Neurosci 12, 2549–54.

    PubMed  CAS  Google Scholar 

  • Young SH, Poo MM (1983) Spontaneous release of transmitter from growth cones of embryonic neurones. Nature 305, 634–7.

    Article  PubMed  CAS  Google Scholar 

  • Ziv NE, Smith SJ (1996) Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan

    Shigeo Okabe

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Okabe, S. Birth, growth and elimination of a single synapse. Anato Sci Int 77, 203–210 (2002). https://doi.org/10.1046/j.0022-7722.2002.00030.x

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  • DOI: https://doi.org/10.1046/j.0022-7722.2002.00030.x

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