Journal of Computational Neuroscience

, Volume 16, Issue 3, pp 251–256 | Cite as

Spatial Localization of Synapses Required for Supralinear Summation of Action Potentials and EPSPs

  • Hidetoshi Urakubo
  • Takeshi Aihara
  • Shinya Kuroda
  • Masataka Watanabe
  • Shunsuke Kondo


Although the supralinear summation of synchronizing excitatory postsynaptic potentials (EPSPs) and backpropagating action potentials (APs) is important for spike-timing-dependent synaptic plasticity (STDP), the spatial conditions of the amplification in the divergent dendritic structure have yet to be analyzed. In the present study, we simulated the coincidence of APs with EPSPs at randomly determined synaptic sites of a morphologically reconstructed hippocampal CA1 pyramidal model neuron and clarified the spatial condition of the amplifying synapses. In the case of uniform conductance inputs, the amplifying synapses were localized in the middle apical dendrites and distal basal dendrites with small diameters, and the ratio of synapses was unexpectedly small: 8–16% in both apical and basal dendrites. This was because the appearance of strong amplification requires the coincidence of both APs of 3–30 mV and EPSPs of over 6 mV, both of which depend on the dendritic location of synaptic sites. We found that the localization of amplifying synapses depends on A-type K+ channel distribution because backpropagating APs depend on the A-type K+ channel distribution, and that the localizations of amplifying synapses were similar within a range of physiological synaptic conductances. We also quantified the spread of membrane amplification in dendrites, indicating that the neighboring synapses can also show the amplification. These findings allowed us to computationally illustrate the spatial localization of synapses for supralinear summation of APs and EPSPs within thin dendritic branches where patch clamp experiments cannot be easily conducted.

spike-timing dependent synaptic plasticity membrane potential amplification synaptic localization multi-compartment model 


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  1. Abbott LF, Nelson SB (2000) Synaptic plasticity: Taming the beast. Nat. Neurosci. 3(Suppl): 1178-1183.Google Scholar
  2. Amaral DG, Witter MP (1995) Hippocampal Formation. In: Paxinos G, ed. The Rat Nervous System. Academic Press, pp. 443-493.Google Scholar
  3. Andrasfalvy BK, Magee JC (2001) Distance-dependent increase in AMPA receptor number in the dendrites of adult hippocampal CA1 pyramidal neurons. J. Neurosci. 21: 9151-9159.Google Scholar
  4. Bannister NJ, Larkman AU (1995a) Dendritic morphology of CA1 pyramidal neurones from the rat hippocampus: II. Spine distributions. J. Comp. Neurol. 360: 161-171.Google Scholar
  5. Bannister NJ, Larkman AU (1995b) Dendritic morphology of CA1 pyramidal neurones from the rat hippocampus: I. Branching patterns. J. Comp. Neurol. 360: 150-160.Google Scholar
  6. Bi GQ, Poo MM (1998) Synaptic modifications in cultured hippocampal neurons: Dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18: 10464-10472.Google Scholar
  7. Bi GQ, Poo MM (2001) Synaptic modification by correlated activity: Hebb's postulate revisited. Annu. Rev. Neurosci. 24: 139-166.Google Scholar
  8. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232: 331-356.Google Scholar
  9. Cannon RC, Turner DA, Pyapali GK, Wheal HV (1998) An online archive of reconstructed hippocampal neurons. J. Neurosci. Methods. 84: 49-54.Google Scholar
  10. Colbert CM, Johnston D (1996) Axonal action-potential initiation and Na+channel densities in the soma and axon initial segment of subicular pyramidal neurons. J. Neurosci. 16: 6676-6686.Google Scholar
  11. Engert F, Bonhoeffer T (1997) Synapse specificity of long-term potentiation breaks down at short distances. Nature 388: 279-284.Google Scholar
  12. Frick A, Magee J, Koester H, Migliore M, Johnston D (2003) Normalization of Ca2+signals by small oblique dendrites of CA1 pyramidal neurons. J. Neurosci. 23: 3243-3250.Google Scholar
  13. Golding NL, Kath WL, Spruston N (2001) Dichotomy of actionpotential backpropagation in CA1 pyramidal neuron dendrites. J. Neurophysiol. 86: 2998-3010.Google Scholar
  14. Golding NL, Staff NP, Spruston N (2002) Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418: 326-331.Google Scholar
  15. Hebb D (1949) The Organization of Behavior. Wiley, New York.Google Scholar
  16. Hines ML, Carnevale NT (1997) The NEURON simulation environment. Neural Comput. 9: 1179-1209.Google Scholar
  17. Hoffman DA, Magee JC, Colbert CM, Johnston D (1997) K+channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387: 869-875.Google Scholar
  18. Karmarkar UR, Najarian MT, Buonomano DV (2002) Mechanisms and significance of spike-timing dependent plasticity. Biol. Cybern. 87: 373-382.Google Scholar
  19. Hoffman DA, Johnston D (1998) Down regulation of transient K+channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC. J. Neurosci. 18: 3521-3528.Google Scholar
  20. Hoffman DA, Johnston D (1999) Neuromodulation of dendritic action potentials. J. Neurophysiol. 81: 408-411.Google Scholar
  21. Magee JC, Johnston D (1995) Characterization of single voltage gated Na+and Ca2+channels in apical dendrites of rat CA1 pyramidal neurons. J. Physiol. 487: 67-90.Google Scholar
  22. Magee JC, Johnston D (1997) A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275: 209-213.Google Scholar
  23. Magee JC, Cook EP (2000) Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons. Nat. Neurosci. 3: 895-903.Google Scholar
  24. Markram H, Lubke J, Frotscher M, Sakmann B (1997) Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275: 213-215.Google Scholar
  25. Migliore M, Shepherd GM (2002) Emerging rules for the distributions of active dendritic conductances. Nat. Rev. Neurosci. 3: 362-370.Google Scholar
  26. Migliore M, Hoffman DA, Magee JC, Johnston D (1999) Role of an A-type K+conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. J. Comput. Neurosci. 7: 5-15.Google Scholar
  27. Nishiyama M, Hong K, Mikoshiba K, Poo MM, Kato K (2000) Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408: 584-588.Google Scholar
  28. Pyapali GK, Sik A, Penttonen M, Buzsaki G, Turner DA (1998) Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: Intracellular staining in vivo and in vitro. J. Comp. Neurol. 391: 335-352. [The data are available at http: //]Google Scholar
  29. Rall W (1962a) Electrophysiology of a dendritic neuron model. Biophysical. J. 2: 145-167.Google Scholar
  30. Rall W (1962b) Theory of physiological properties of dendrites. Annals of New York Academy of Science 96: 1071-1092.Google Scholar
  31. Remondes M, Schuman EM (2002) Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons. Nature 416: 736-740.Google Scholar
  32. Sabatini BL, Maravall M, Svoboda K (2001) Ca(2+) signaling in dendritic spines. Curr. Opin. Neurobiol. 11: 349-356.Google Scholar
  33. Shouval HZ, Bear MF, Cooper LN (2002)A unified model of NMDA receptor-dependent bidirectional synaptic plasticity. Proc. Natl. Acad. Sci. USA 99: 10831-10836.Google Scholar
  34. Spruston N, Jonas P, Sakmann B (1995a) Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. J. Physiol. 482: 325-352.Google Scholar
  35. Spruston N, Schiller Y, Stuart G, Sakmann B (1995b) Activity dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268: 297-300.Google Scholar
  36. Stuart G, Hausser M (1994) Initiation and spread of sodium action potentials in cerebellar Purkinje cells. Neuron. 13: 703-712.Google Scholar
  37. Stuart GJ, Sakmann B (1994) Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367: 69-72.Google Scholar
  38. Stuart GJ, Hausser M (2001) Dendritic coincidence detection of EPSPs and action potentials. Nat. Neurosci. 4: 63-71.Google Scholar
  39. Tsubokawa H, Ross WN (1996) IPSPs modulate spike backpropagation and associated [Ca2+]ichanges in the dendrites of hippocampal CA1 pyramidal neurons. J. Neurophysiol. 76: 2896-2906.Google Scholar
  40. Tuckwell HC (1988) Introduction to Theoretical Neurobiology: Cambridge University Press.Google Scholar
  41. Watanabe S, Hoffman DA, Migliore M, Johnston D (2002) Dendritic K+channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons. Proc. Natl. Acad. Sci. USA 99: 8366-8371.Google Scholar
  42. Zhang LI, Tao HW, Holt CE, Harris WA, Poo M (1998) A critical window for cooperation and competition among developing retinotectal synapses. Nature 395: 37-44.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Hidetoshi Urakubo
    • 1
  • Takeshi Aihara
    • 2
  • Shinya Kuroda
    • 3
  • Masataka Watanabe
    • 4
  • Shunsuke Kondo
    • 4
  1. 1.Department of Quantum Engineering and Systems Science, Graduate School of EngineeringUniversity of TokyoBunkyo-kuJapan
  2. 2.Department of Information and Communication Engineering, Faculty of EngineeringUniversity of TamagawaMachidaJapan
  3. 3.Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Information Science and TechnologyUniversity of Tokyo, PRESTO, Japan Science and TechnologyBunkyo-kuJapan
  4. 4.Department of Quantum Engineering and Systems Science, Graduate School of EngineeringUniversity of TokyoBunkyo-kuJapan

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