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Random dispersion in excitatory synapse response

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Abstract

The excitatory synaptic function is subject to a huge amount of researches and fairly all the structural elements of the synapse are investigated to determine their specific contribution to the response. A model of an excitatory (hippocampal) synapse, based on time discretized Langevin equations (time-step = 40 fs), was introduced to describe the Brownian motion of Glutamate molecules (GLUTs) within the synaptic cleft and their binding to postsynaptic receptors. The binding has been computed by the introduction of a binding probability related to the hits of GLUTs on receptor binding sites. This model has been utilized in computer simulations aimed to describe the random dispersion of the synaptic response, evaluated from the dispersion of the peak amplitude of the excitatory post-synaptic current. The results of the simulation, presented here, have been used to find a reliable numerical quantity for the unknown value of the binding probability. Moreover, the same results have shown that the coefficient of variation decreases when the number of postsynaptic receptors increases, all the other parameters of the process being unchanged. Due to its possible relationships with the learning and memory, this last finding seems to furnish an important clue for understanding the basic mechanisms of the brain activity.

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References

  • Agmon N, Edelstein AL (1997) Collective binding properties of receptor arrays. Biophys J 72:1582–1594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Anggono V, Huganir RL (2012) Regulation of AMPA receptor trafficking and synaptic plasticity. Curr Opin Neurobiol 22:461–469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Araç D, Boucard AA, Ozkan E, Strop P, Newell E, Südhof TC, Brunger AT (2007) Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein–protein and protein–Ca2+ interactions. Neuron 56:992–1003

    Article  PubMed  Google Scholar 

  • Armstrong N, Gouaux E (2000) Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron 28:165–181

    Article  CAS  PubMed  Google Scholar 

  • Clements JD, Lester RA, Tong J, Jahr CE, Westbrook GL (1992) The time course of glutamate in the synaptic cleft. Science 258:11498–11501

    Article  Google Scholar 

  • Clopath C (2012) Synaptic consolidation: an approach to long-term learning. Cogn Neurodyn 6(3):251–257

    Article  PubMed Central  PubMed  Google Scholar 

  • Diamond JS, Jahr CE (1997) Transporters buffer synaptically released glutamate on a submillisecond time scale. J Neurosci 17(12):4672–4687

    CAS  PubMed  Google Scholar 

  • Forti L, Bossi M, Bergamaschi A, Villa A, Malgaroli A (1997) Loose-patch recordings of single quanta at individual hippocampal synapses. Nature 388:874–878

    Article  CAS  PubMed  Google Scholar 

  • Freche D, Pannasch U, Rouach N, Holcman D (2011) Synapse geometry and receptor dynamics modulate synaptic strength. PLoS One 6(10):e25122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gegelashvili G, Dehnes Y, Danbolt NC, Schousboe A (2000) The high-affinity Glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Neurochem Int 37:163–170

    Article  CAS  PubMed  Google Scholar 

  • Gillespie DT (1996) The mathematics of Brownian motion and Johnson noise. Am J Phys 64:225–240

    Article  Google Scholar 

  • Hayashi H, Igarashi J (2009) LTD windows of the STDP learning rule and synaptic connections having a large transmission delay enable robust sequence learning amid background noise. Cogn Neurodyn 3(2):119–130

    Article  PubMed Central  PubMed  Google Scholar 

  • Jonas P, Major G, Sakmann B (1993) Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J Physiol Lond 472 C:615–663

    Google Scholar 

  • Jonas P, Spruston N (1994) Mechanisms shaping glutamate-mediated excitatory post-synaptic currents in the CNS. Curr Opin Neurobiol 4:366–372

    Article  CAS  PubMed  Google Scholar 

  • Kleppe IC, Robinson HP (1999) Determining the activation time course of synaptic AMPA receptors from openings of colocalized NMDA receptors. Biophys J 77:1418–1427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu G, Choi S, Tsien RW (1999) Variability of neurotransmitter concentration and nonsaturation of post-synaptic AMPA receptor at synapses in hippocampal cultures and slices. Neuron 22:395–409

    Article  CAS  PubMed  Google Scholar 

  • Longsworth LG (1953) Diffusion measurements at 25°C of aqueous solutions of amino acids, peptides and sugars. J Am Chem Soc 75:5705–5709

    Article  CAS  Google Scholar 

  • Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa T (2010) The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors. Mol Neurobiol 42:161–184

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rabie HR, Rong J, Glavinović MI (2006) Monte Carlo simulation of release of vesicular content in neuroendocrine cells. Biol Cybern 94:483–499

    Article  CAS  PubMed  Google Scholar 

  • Savtchenko LP, Rusakov DA (2007) The optimal height of the synaptic cleft. Proc Natl Acad Sci USA 104:1823–1828

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Santos SD, Carvalho AL, Caldeira MV, Duarte CB (2009) Regulation of AMPA receptors and synaptic plasticity. Neuroscience 158:105–125

    Article  CAS  PubMed  Google Scholar 

  • Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Müller CS, Bildl W, Baehrens D, Hüber B, Kulik A, Klöcker N, Schulte U, Fakler B (2012) High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron 74:621–633

    Article  CAS  PubMed  Google Scholar 

  • Sobolevsky AI, Rosconi MP, Gouaux E (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype Glutamate receptor. Nature 462:745–756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stevens CF (2003) Neurotransmitter release at central synapses. Neuron 40(2):381–388

    Article  CAS  PubMed  Google Scholar 

  • Takumi Y, Matsubara A, Rinvik E, Ottersen OP (1999) The arrangement of glutamate receptors in excitatory synapses. Ann NY Acad Sci 868:474–482

    Article  CAS  PubMed  Google Scholar 

  • Tichelaar W, Safferling M, Keinnen K, Stark H, Madden DR (2004) The three-dimensional structure of an ionotropic glutamate receptor reveals a dimer-of-dimers assembly. J Mol Biol 344:435–442

    Article  CAS  PubMed  Google Scholar 

  • Trommershäuser J, Titz S, Keller BU, Zippelius A (2001) Variability of excitatory currents due to single-channel noise, receptor number and morphological heterogeneity. J Theor Biol 208:329–343

    Article  PubMed  Google Scholar 

  • Uteshev VV, Pennefather PS (1996) A mathematical description of miniature post-synaptic current generation at central nervous system synapses. Biophys J 71:1256–1266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ventriglia F (1973) Kinetic approach to neural systems. Int J Neurosci 6:29–30

    Article  CAS  PubMed  Google Scholar 

  • Ventriglia F (1974) Kinetic approach to neural systems I. Bull Math Biol 36:535–544

    Article  CAS  PubMed  Google Scholar 

  • Ventriglia F, Di Maio V (2000) A Brownian simulation model of glutamate synaptic diffusion in the femtosecond time scale. Biol Cybern 83:93–109

    Article  CAS  PubMed  Google Scholar 

  • Ventriglia F, Di Maio V (2003) Stochastic fluctuations of the quantal EPSC amplitude in computer simulated excitatory synapses of hippocampus. Biosystems 71:195–204

    Article  PubMed  Google Scholar 

  • Ventriglia F (2004) Saturation in excitatory synapses of hippocampus investigated by computer simulations. Biol Cybern 90:349–359

    Article  PubMed  Google Scholar 

  • Ventriglia F (2008) The engram formation and the global oscillations of CA3. Cogn Neurodyn 2:335–345

    Article  PubMed Central  PubMed  Google Scholar 

  • Ventriglia F (2011) Effect of filaments within the synaptic cleft on the response of excitatory synapses simulated by computer experiments. Biosystems 104:14–22

    Article  PubMed  Google Scholar 

  • Ventriglia F, Di Maio V (2013a) Effects of AMPARs trafficking and glutamate-receptors binding probability on stochastic variability of EPSC. Biosystems 112:298–304

    Article  CAS  PubMed  Google Scholar 

  • Ventriglia F, DiMaio V (2013b) Glutamate–AMPAR interaction in a model of synaptic transmission. Brain Res 1536:168–176

    Article  CAS  PubMed  Google Scholar 

  • Wahl LM, Pouzat C, Stratford KJ (1996) Monte Carlo simulation of fast excitatory synaptic transmission at a hippocampal synapse. J Neurophysiol 75:597–608

    CAS  PubMed  Google Scholar 

  • Zuber B, Nikonenko I, Klauser P, Muller D, Dubochet J (2005) The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes. Proc Natl Acad Sci USA 102:19192–19197

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Francesco Ventriglia.

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Ventriglia, F. Random dispersion in excitatory synapse response. Cogn Neurodyn 8, 327–334 (2014). https://doi.org/10.1007/s11571-014-9285-1

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  • DOI: https://doi.org/10.1007/s11571-014-9285-1

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