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Modelling zinc changes at the hippocampal mossy fiber synaptic cleft

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Abstract

Zinc, a transition metal existing in very high concentrations in the hippocampal mossy fibers from CA3 area, is assumed to be co-released with glutamate and to have a neuromodulatory role at the corresponding synapses. The synaptic action of zinc is determined both by the spatiotemporal characteristics of the zinc release process and by the kinetics of zinc binding to sites located in the cleft area, as well as by their concentrations. This work addresses total, free and complexed zinc concentration changes, in an individual synaptic cleft, following single, short and long periods of evoked zinc release. The results estimate the magnitude and time course of the concentrations of zinc complexes, assuming that the dynamics of the release processes are similar to those of glutamate. It is also considered that, for the cleft zinc concentrations used in the model (≤ 1 μM), there is no postsynaptic zinc entry. For this reason, all released zinc ends up being reuptaken in a process that is several orders of magnitude slower than that of release and has thus a much smaller amplitude. The time derivative of the total zinc concentration in the cleft is represented by the difference between two alpha functions, corresponding to the released and uptaken components. These include specific parameters that were chosen assuming zinc and glutamate co-release, with similar time courses. The peak amplitudes of free zinc in the cleft were selected based on previously reported experimental cleft zinc concentration changes evoked by single and multiple stimulation protocols. The results suggest that following a low amount of zinc release, similar to that associated with one or a few stimuli, zinc clearance is mainly mediated by zinc binding to the high-affinity sites on the NMDA receptors and to the low-affinity sites on the highly abundant GLAST glutamate transporters. In the case of higher zinc release brought about by a larger group of stimuli, most zinc binding occurs essentially to the GLAST transporters, having the corresponding zinc complex a maximum concentration that is more than one order of magnitude larger than that for the high and low affinity NMDA sites. The other zinc complexes considered in the model, namely those formed with sites on the AMPA receptors, calcium and KATP channels and with ATP molecules, have much smaller contributions to the synaptic zinc clearance.

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References

  • Assaf, S., & Chung, S. (1984). Release of endogenous Zn2+ from brain tissue during activity. Nature, 308, 734–736.

    Article  CAS  PubMed  Google Scholar 

  • Bancila, V., Nikonenko, I., Dunant, Y., & Bloc, A. (2004). Zinc inhibits glutamate release via activation of pre-synaptic KATP channels and reduces ischaemic damage in rat hippocampus. Journal of Neurochemistry, 90, 1243–1250.

    Article  CAS  PubMed  Google Scholar 

  • Bischofberger, J., Engel, D., Frotscher, M., & Jonas, P. (2006). Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network. European Journal of Phycology. doi:10.1007/s00424-006-0093-2.

    Google Scholar 

  • Bloc, A., Cens, T., Cruz, H., & Dunant, Y. (2000). Zinc-induced changes in ionic currents of clonal rat pancreatic-cells: activation of ATP-sensitive K+ channels. The Journal of Physiology, 529, 723–734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Budde, T., Minta, A., White, J. A., & Kay, A. R. (1997). Imaging free zinc in synaptic terminals in live hippocampal slices. Neuroscience, 79, 347–358.

  • Bourne, J. N., & Harris, K. M. (2007). Dendritic spines. eLS. doi:10.1002/9780470015902.a0000093.pub2.

  • Büsselberg, D., Michael, D., Evans, M., Carpenter, O., & Haas, H. (1992). Zinc (Zn 2+) blocks voltage gated calcium channels in cultured rat dorsal root ganglion cells. Brain Research, 593, 77–81.

    Article  PubMed  Google Scholar 

  • Büsselberg, D., Platt, B., Michael, D., Carpenter, O., & Haas, H. (1994). Mammalian voltage-activated calcium channel currents are blocked by Pb2+, Zn2+, and Al3+. The Journal of Physiology, 71, 1491–1497.

    Google Scholar 

  • Canzoniero, L., Sensi, S., & Choi, D. (1997). Measurement of intracellular free zinc in living neurons. Neurobiology of Disease, 4, 275–279.

    Article  CAS  PubMed  Google Scholar 

  • Chicurel, M. E., & Harris, K. M. (1992). Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. The Journal of Comparative Neurology, 325, 169–182.

    Article  CAS  PubMed  Google Scholar 

  • Cho, I., Im, J., Kim, D., Kim, K., Lee, J., & Han, P. (2003). Protective effects of extracellular glutathione against Zn2 + −induced cell death in vitro and in vivo. Journal of Neuroscience Research, 74, 736–743.

    Article  CAS  PubMed  Google Scholar 

  • Clements, J. (1996). Transmitter timecourse in the synaptic cleft: its role in central synaptic function. Trends in Neurosciences, 19, 163–171.

    Article  CAS  PubMed  Google Scholar 

  • Clements, J., Lester, R., Tong, G., Jahr, C., & Westbrook, G. (1992). The time course of glutamate in the synaptic cleft. Science, 258, 1498–1501.

    Article  CAS  PubMed  Google Scholar 

  • Colvin, R. A., Fontaine, C. P., Laskowski, M., & Thomas, D. (2003). Zn2+ transporters and Zn2+ homeostasis in neurons Eur. Journal de Pharmacologie, 479, 171–185.

    CAS  Google Scholar 

  • Colvin, R., Bush, A., Volitakis, I., Fontaine, C., Thomas, D., Kikuchi, K., & Holmes, W. (2008). Insights into Zn2+ homeostasis in neurons from experimental and modeling studies. American Journal of Physiology. Cell Physiology, 294, 726–742.

    Article  Google Scholar 

  • Conti, R., & Lisman, J. (2003). The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: evidence for multiquantal release. Proceedings of the National Academy of Sciences of the United States of America, 100, 4885–4890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Danbolt, N. C. (2001). Glutamate uptake. Progress in Neurobiology, 65, 1–105.

  • Dehnes, Y., Chaudhry, F. A., Ullensvang, K., Lehre, K. P., Storm-Mathisen, J., & Danbolt, N. C. (1998). The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated Chloride Channel concentrated near the synapse in parts of the dendritic membrane facing Astroglia. The Journal of Neuroscience, 18, 3606–3619.

    CAS  PubMed  Google Scholar 

  • Dineley, K., Malaiyandi, L., & Reynolds, I. (2002). A reevaluation of neuronal zinc measurements: artifacts associated with high intracellular dye concentration. Molecular Pharmacology, 62, 618–627.

    Article  CAS  PubMed  Google Scholar 

  • Erreger, K., & Traynellis, S. F. (2005). Allosteric interaction between zinc and glutamate binding domains on NR2A causes desensitization of NMDA receptors. The Journal of Physiology, 569, 381–393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franks, K., Bartol, T., & Sejnowski, T. (2002). A Monte Carlo model reveals independent signaling at central glutamatergic synapses. Biophysical Journal, 83, 2333–2348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fraústo da Silva, J. J. R., & Williams, R. J. P. (1991). The biological chemistry of the elements. The inorganic chemistry of life. New York: Oxford University Press.

    Google Scholar 

  • Frederickson, C. (1989). Neurobiology of zinc and zinc-containing neurons. International Review of Neurobiology, 31, 145–238.

    Article  CAS  PubMed  Google Scholar 

  • Frederickson, C. J., Suh, S. W., Silva, D., Frederickson, C. J., & Thomson, R. B. (2000). Importance of zinc in the central nervous system: the zinc-containing neuron. The Journal of Nutrition, 130, 1471–1478.

    Google Scholar 

  • Frederickson, C. J., Koh, J. Y., & Bush, A. I. (2005). The neurobiology of zinc in health and disease. Nature Reviews. Neuroscience, 6, 449–462.

    Article  CAS  PubMed  Google Scholar 

  • Furuta, A., Martin, L. J., Lin, C. L., Dykes-Hoberg, M., & Rothstein, J. D. (1997). Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience, 81, 1031–1042.

    Article  CAS  PubMed  Google Scholar 

  • Gao, X.-M., Sakai, K., Roberts, R., Dean, B., & Tamminga, C. (2000). Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in Subregions of human hippocampus: effects of schizophrenia. The American Journal of Psychiatry, 157(7), 1141–1149.

    Article  CAS  PubMed  Google Scholar 

  • Grauert, A., Engel, D. A., & Ruiz, A. J. (2014). Endogenous zinc depresses GABAergic transmission via T-type Ca(2+) channels and broadens the time window for integration of glutamatergic inputs in dentate granule cells. The Journal of Physiology, 592, 67–86.

    Article  CAS  PubMed  Google Scholar 

  • Hallermann, S., Pawlu, C., Jonas, P., & Heckmann, M. (2003). A large pool of releasable vesicles in a cortical glutamatergic synapse. PNAS, 100, 8975–8980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris, K. M., & Sultan, P. (1995). Variation in number, location and size of synaptic vesicles provides an anatomical basis for the Nonuniform probability of release at hippocampal CA1 synapses. Neuropharmacology, 34, 1387–1395.

    Article  CAS  PubMed  Google Scholar 

  • Harrison, N. L., & Gibbons, S. J. (1994). Zn2+: an endogenous modulator of ligand- and voltage-gated ion channels. Neuropharmacology, 33, 935–952.

    Article  CAS  PubMed  Google Scholar 

  • Hell, J., Westenbroek, R., Warner, C., Ahlijanian, M., Prystay, W., et al. (1993). Identification and differential subcellular localization of the neuronal class C and class D L-type Calcium Channel α subunits. The Journal of Cell Biology, 123, 949–962.

    Article  CAS  PubMed  Google Scholar 

  • Hires, S., Zhu, Y., & Tsien, R. (2008). Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proceedings of the National Academy of Sciences of the United States of America, 105, 4411–4416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howell, G., Welch, M., & Frederickson, C. (1984). Stimulation-induced uptake and release of zinc in hippocampal slices. Nature, 308, 736–738.

    Article  CAS  PubMed  Google Scholar 

  • Huang, E. (1997). Metal ions and synaptic transmission: think zinc. Proceedings of the National Academy of Sciences of the United States of America, 94, 13386–13387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, L., & Tepaamorndech, S. (2013). The SLC30 family of zinc transporters – a review of current understanding of their biological and pathophysiological roles. Molecular Aspects of Medicine, 34, 548–560.

    Article  CAS  PubMed  Google Scholar 

  • Jacob, C., Maret, W., & Vallee, B. (1998). Control of zinc transfer between thionein, metallothionein, and zinc proteins. Proceedings of the National Academy of Sciences of the United States of America, 95, 3483–3488.

    Article  Google Scholar 

  • Jiang, L., Maret, W., & Vallee, B. (1998). The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase. Proceedings of the National Academy of Sciences of the United States of America, 95, 3483–3488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones, O., Bernstein, G., Jones, E., Jugloff, D., Law, M., et al. (1997). N-type calcium channels in the developing rat hippocampus: subunit, complex, and regional expression. The Journal of Neuroscience, 17, 6152–6164.

    CAS  PubMed  Google Scholar 

  • Kariuki, S., & Dewald, H. (1996). Evaluation of diffusion coefficients of metallic ions in aqueous solutions. Electroanalysis, 8, 307–313.

    Article  CAS  Google Scholar 

  • Kay, A. (2003). Evidence for chelatable zinc in the extracellular space of the hippocampus, but little evidence for synaptic release of Zn. The Journal of Neuroscience, 23, 6847–6855.

    CAS  PubMed  Google Scholar 

  • Kessler, J. P. (2013). Control of cleft glutamate concentration and glutamate spill-out by Perisynaptic glia: uptake and diffusion barriers. PloS One, 8(8), e70791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ketterman, J., & Li, Y. (2008). Presynaptic evidence for zinc release at the mossy fiber synapse of rat hippocampus. Journal of Neuroscience Research, 86, 422–434.

    Article  CAS  PubMed  Google Scholar 

  • Khan, M., Goldsmith, C. R., Huang, Z., Georgiou, J., Luyben, T. T., Roder, J. C., Lippard, S. J., & Okamoto, K. (2014). Two-photon imaging of Zn2+ dynamics in mossy fiber boutons of adult hippocampal slices. Proceedings of the National Academy of Sciences of the United States of America, 111, 6786–6791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krezel, A., Hao, Q., & Maret, W. (2007). The zinc/thiolate redox biochemistry of metallothionein and the control of zinc ion fluctuations in cell signaling. Archives of Biochemistry and Biophysics, 463, 188–200.

    Article  CAS  PubMed  Google Scholar 

  • Lehre, K., & Danbolt, N. (1998). The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. The Journal of Neuroscience, 18, 8751–8757.

    CAS  PubMed  Google Scholar 

  • Li, Y., Hough, C. J., Suh, S. W., Sarvey, J. M., & Frederickson, C. J. (2001a). Rapid translocation of Zn(2+) from presynaptic terminals into postsynaptic hippocampal neurons after physiological stimulation. Journal of Neurophysiology, 86, 2597–2604.

    CAS  PubMed  Google Scholar 

  • Li, Y., Hough, C. J., Frederickson, C. J., & Sarvey, J. M. (2001b). Induction of mossy fiber -- > Ca3 long-term potentiation requires translocation of synaptically released Zn2 +. The Journal of Neuroscience, 21, 8015–8025.

    CAS  PubMed  Google Scholar 

  • Lin, D., Cohen, A., & Coulter, D. (2001). Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor responses in hippocampal CA3 neurons. Journal of Neurophysiology, 85, 1185–1196.

    CAS  PubMed  Google Scholar 

  • Malenka, R. C., & Bear, M. F. (2004). LTP and LTD: an embarrassment of riches. Neuron, 44, 5–21.

    Article  CAS  PubMed  Google Scholar 

  • Marin, P., Israel, M., Glowinski, J., & Premont, J. (2000). Routes of zinc entry in mouse cortical neurons: role in zinc-induced neurotoxicity. The European Journal of Neuroscience, 12, 8–18.

    Article  CAS  PubMed  Google Scholar 

  • Masters, B. A., Quaife, Q. C., Erickson, J. C., Kelly, E. J., Froelick, G. J., Zambrowicz, B. P., Brinster, R. L., & Palmiter, R. D. (1994). Metallothionein ill is expressed in neurons that sequester zinc in synaptic vesicles. The Journal of Neuroscience, 14, 5844–5857.

    CAS  PubMed  Google Scholar 

  • Melani, A., Turchi, A., Vannucchi, M., Cipriani, C., Gianfriddo, M., et al. (2005). ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochemistry International, 47, 442–448.

    Article  CAS  PubMed  Google Scholar 

  • Mitrovic, A. D., Plesko, F., & Vandenberg, R. J. (2001). Zn2+ inhibits the anion conductance of the glutamate transporter EAAT4. The Journal of Biological Chemistry, 276, 26071–26076.

    Article  CAS  PubMed  Google Scholar 

  • Molnar, E. (2011). Long-term potentiation in cultured hippocampal neurons. Seminars in Cell and Developmental Biology, 22, 506–513.

    Article  CAS  PubMed  Google Scholar 

  • Mott, D., Beneviste, M., & Dingledine, R. (2008). pH-dependent inhibition of kainite receptors by zinc. The Journal of Neuroscience, 13, 1659–1671.

    Article  Google Scholar 

  • Nicoll, R. A., & Schmitz, D. (2005). Synaptic plasticity at hippocampal mossy fibre synapses. Nature Reviews. Neuroscience, 6, 863–876.

    Article  CAS  PubMed  Google Scholar 

  • Nusser, Z., Lujan, R., Laube, G., Roberts, J. D., Molnar, E., & Somogyi, P. (1998). Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron, 21, 545–559.

  • Paoletti, P., Arscher, P., & Neyton, C. (1997). High-affinity zinc inhibition of NMDA NR1–NR2A receptors. The Journal of Neuroscience, 17, 5711–5725.

    CAS  PubMed  Google Scholar 

  • Paoletti, P., Vergnano, A., Barbour, A., & Casado, M. (2009). Review: zinc at glutamatergic synapses. Neuroscience, 158, 126–136.

    Article  CAS  PubMed  Google Scholar 

  • Paoletti, P., Bellone, C., & Zhou, Q. (2013). NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nature Reviews. Neuroscience, 14, 383–400.

    Article  CAS  PubMed  Google Scholar 

  • Perez-Clausell, J., & Danscher, G. (1985). Intravesicular localization of zinc in rat telencephalic boutons: a histochemical study. Brain Research, 337, 91–98.

    Article  CAS  PubMed  Google Scholar 

  • Press, W. H., Teukolsky, S. A., Vetterling, W. T., & Flannery, B. P. (1992). Numerical recipes in Fortran. Cambridge: The Art of Scientific Computing. Second Edition. University Press.

    Google Scholar 

  • Qian, J., & Noebels, J. L. (2005). Visualization of transmitter release with zinc fluorescencedetection at the mouse hippocampal mossy fibre synapse. The Journal of Physiology, 566, 747–758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinta-Ferreira, M. E., & Matias, C. M. (2005). Tetanically released zinc inhibits hippocampal mossy fiber calcium, zinc and postsynaptic responses. Brain Research, 1047, 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Quinta-Ferreira, M. E., Matias, C. M., Arif, M., & Dionísio, J. C. (2004). Measurement of presynaptic zinc changes in hippocampal mossy fibers. Brain Research, 1026, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Rassendren, F.-A., Lory, P., Pin, J.-P., & Nargeot, J. (1990). Zinc has opposite effects on NMDA and Non-NMDA receptors expressed in xenopus oocytes. Neuron, 4, 733–740.

  • Rollenhagen, A., & Lübke, J. H. R. (2010). The mossy fiber Bouton: the “common” or the “unique” synapse? Front Synaptic Neurosci. doi:10.3389/fnsyn.2010.00002.

    PubMed  PubMed Central  Google Scholar 

  • Rollenhagen, A., Sätzler, K., Rodríguez, E. P., Jonas, P., Frotscher, M., & Lübke, J. H. (2007). Structural determinants of transmission at large hippocampal mossy fiber synapses. The Journal of Neuroscience, 27, 10434–10444.

    Article  CAS  PubMed  Google Scholar 

  • Ruiz, A., Walker, M., Fabian-Fine, R., & Kullmann, D. (2004). Endogenous zinc inhibits GABA(a) receptors in a hippocampal pathway. Journal of Neurophysiology, 91, 1091–1096.

    Article  CAS  PubMed  Google Scholar 

  • Savtchenko, L. P., & Rusakov, D. A. (2004). Glutamate escape from a tortuous synaptic cleft of the hippocampal mossy fibre synapse. Neurochemistry International, 45, 479–484.

    Article  CAS  PubMed  Google Scholar 

  • Savtchenko, L. P., & Rusakov, D. A. (2008). The optimal height of the synaptic cleft. Proceedings of the National Academy of Sciences of the United States of America, 104, 1823–1828.

    Article  Google Scholar 

  • Scimemi, A., & Beato, B. (2009). Determining the neurotransmitter concentration profile at active synapses. Molecular Neurobiology, 40, 289–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sensi, S., Canzoniero, L., Shen, P., Howard, S., Koh, J., et al. (1997). Measurement of intracellular free zinc in living cortical neurons: routes of entry. The Journal of Neuroscience, 17, 9554–9564.

    CAS  PubMed  Google Scholar 

  • Sensi, S., Paoletti, P., Koh, J., Aizenman, E., Bush, A., & Hershfinkel, M. (2011). The neurophysiology and pathology of brain zinc. The Journal of Neuroscience, 31, 16076–16085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smart, T., Xie, X., & Krishek, B. (1994). Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc. Progress in Neurobiology, 42, 393–441.

    Article  CAS  PubMed  Google Scholar 

  • Südhof, T. (1995). The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature, 375, 645–653.

    Article  PubMed  Google Scholar 

  • Thompson, R. B., Peterson, D., Mahoney, W., Cramer, M., Maliwal, B. P., Suh, S. W., Frederickson, C., Fierke, C., & Herman, P. (2002). Fluorescent zinc indicators for neurobiology. Journal of Neuroscience Methods, 118, 63–75.

    Article  CAS  PubMed  Google Scholar 

  • Ueno, S., Tsukamoto, M., Hirano, T., Kikuchi, K., Yamada, M., et al. (2002). Mossy fiber Zn2+ spillover modulates heterosynaptic N-methyl-d-aspartate receptor activity in hippocampal CA 3 circuits. The Journal of Cell Biology, 158, 215–220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vallee, B., & Falchuk, K. (1993). The biochemical basis of zinc physiology. Physiological Reviews, 73, 79–118.

    CAS  PubMed  Google Scholar 

  • Vandenberg, R., Mitrovic, A., & Johnston, G. (1998). Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions. Molecular Pharmacology, 54, 189–196.

    CAS  PubMed  Google Scholar 

  • Vergnano, A., Rebola, N., Savtchenko, L., Pinheiro, P., Casado, M., Kieffer, B., Rusakov, D., Mulle, C., & Paoletti, P. (2014). Zinc dynamics and action at excitatory synapses. Neuron, 82, 1101–1114.

    Article  CAS  PubMed  Google Scholar 

  • Vogt, K., Mellor, J., Tong, G., & Nicoll, R. (2000). The actions of synaptically released zinc at hippocampal mossy fiber synapses. Neuron, 26, 187–196.

    Article  CAS  PubMed  Google Scholar 

  • Wenzel, H., Cole, T., Born, D., & Schwartzkroin, P. (1997). Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. Proceedings of the National Academy of Sciences of the United States of America, 94, 12676–12681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada, W., & Zucker, R. (1992). Time course of transmitter release calculated from stimulations of a calcium diffusion model. Biophysical Journal, 61, 671–682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, S., Studer, D., Chai, X., Graber, W., Brose, N., Nestel, S., Young, C., Rodriguez, E. P., Saetzler, K., & Frostscher, M. (2012). Structural plasticity of spines at giant mossy fiber synapses. Frontiers in Neuronal circuits., 6, 1–7.

    Google Scholar 

  • Zini, S., E., T., Roisin, M. P., & Ben-Ari, Y. (1991). Two binding sites for [3H] glibenclamide in the rat brain. Brain Research, 542, 151–154.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

M. E. Quinta-Ferreira is grateful to Dr. C. C. A. M. Gielen for providing the conditions to start this work, that was funded by strategic project UID/NEU/04539/2013.

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Authors and Affiliations

  1. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, P-3004-504, Coimbra, Portugal

    M. E. Quinta-Ferreira, F. D. S. Sampaio dos Aidos, C. M. Matias, J. C. Dionísio, R. M. Santos & L. M. Rosário

  2. Department of Physics, University of Coimbra, P-3004-516, Coimbra, Portugal

    M. E. Quinta-Ferreira, F. D. S. Sampaio dos Aidos & P. J. Mendes

  3. CFisUC, Department of Physics, University of Coimbra, P-3004-516, Coimbra, Portugal

    F. D. S. Sampaio dos Aidos

  4. UTAD- University of Trás-os-montes and Alto Douro, P-5000-801, Vila Real, Portugal

    C. M. Matias

  5. LIP- Laboratory of Instrumentation and Experimental Particles Physics, P-3004-516, Coimbra, Portugal

    P. J. Mendes

  6. Department of Animal Biology, University of Lisbon, P-1749-016, Lisbon, Portugal

    J. C. Dionísio

  7. Department of Life Sciences, University of Coimbra, P-3004-516, Coimbra, Portugal

    R. M. Santos & L. M. Rosário

  8. CIEPQPF - Research Centre of Chemical Process Engineering and Forest Products, Department of Chemical Engineering, University of Coimbra, P-3030-790, Coimbra, Portugal

    R. M. Quinta-Ferreira

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Quinta-Ferreira, M.E., Sampaio dos Aidos, F.D.S., Matias, C.M. et al. Modelling zinc changes at the hippocampal mossy fiber synaptic cleft. J Comput Neurosci 41, 323–337 (2016). https://doi.org/10.1007/s10827-016-0620-x

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