Journal of Computational Neuroscience

, Volume 33, Issue 2, pp 207–225 | Cite as

On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons

  • Daniela Bianchi
  • Addolorata Marasco
  • Alessandro Limongiello
  • Cristina Marchetti
  • Helene Marie
  • Brunello Tirozzi
  • Michele Migliore
Article

Abstract

Under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. This is a robust effect that is not usually explored in experiments or explicitly implemented or tested in models. However, the range of current strength needed for a depolarization block could be easily reached with a random background activity of only a few hundred excitatory synapses. Depolarization block may thus be an important property of neurons that should be better characterized in experiments and explicitly taken into account in models at all implementation scales. Here we analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single-compartment. The results show the specific ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to a depolarization block. We suggest that this can be one of the rate-limiting mechanisms protecting a CA1 neuron from excessive spiking activity.

Keywords

Depolarization block CA1 pyramidal neuron Bifurcation analysis Kinetics 

Notes

Acknowledgements

Financial support from “Compagnia di San Paolo” is gratefully acknowledged. We thank Drs. S. Cuomo and P. De Michele (Department of Mathematics and Applications “Renato Caccioppoli”, University of Naples Federico II) for assistance in running the parallel version of our morphological model and for the use of the S.Co.P.E. Grid infrastructure of University of Naples Federico II.

References

  1. Andrasfalvy, B. K., & Magee, J.C. (2001). Distance-dependent increase in AMPA receptor number in the dendrites of adult hippocampal CA1 pyramidal neurons. Journal of Neuroscience, 21, 9151–9159.PubMedGoogle Scholar
  2. Ayala, G. F., Dichter, M., Gumnit, R. J., Matsumoto, H., & Spencer, W. A. (1973). Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms. Brain Research, 52, 1–17.PubMedCrossRefGoogle Scholar
  3. Colbert, C. M., & Pan, E. (2002). Ion channel properties underlying axonal action potential initiation in pyramidal neurons. Nature Neuroscience, 5, 533–538.PubMedCrossRefGoogle Scholar
  4. Dichter, M. A., & Ayala, G. F. (1987). Cellular mechanisms of epilepsy: A status report. Science, 237, 157–164.PubMedCrossRefGoogle Scholar
  5. Gasparini, S., & Magee, J. C. (2002). Phosphorylation-dependent differences in the activation properties of distal and proximal dendritic Na  +  channels in rat CA1 hippocampal neurons. Journal of Physiology, 541.3, 665–672.CrossRefGoogle Scholar
  6. Golomb, D., Yue, C., & Yaari, Y. (2006). Contribution of persistent Na  +  current and M-type K  +  current to somatic bursting in CA1 pyramidal cells: Combined experimental and modeling study. Journal of Neurophysiology, 96, 1912–1926.PubMedCrossRefGoogle Scholar
  7. Hassard, B. (1978). Bifurcation of periodic solutions of the Hodgkin–Huxley model for the squid giant axon. Journal of Theoretical Biology, 71, 401–420.PubMedCrossRefGoogle Scholar
  8. Hemond, P., Epstein, D., Boley, A., Migliore, M., Ascoli, G. A., & Jaffe, D. B. (2008). Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b. Hippocampus, 18, 411–424.PubMedCrossRefGoogle Scholar
  9. Hines, M. L., & Carnevale, N. T. (2003). The NEURON simulation environment. In The handbook of brain theory and neural networks (2nd ed., pp. 769–773). Cambridge: MIT Press.Google Scholar
  10. Hoffman, D. A., & Johnston, D. (1998). Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC. Journal of Neuroscience, 18, 3521–3528.PubMedGoogle Scholar
  11. Hoffman, D. A., Magee, J. C., Colbert, C. M., & Johnston, D. (1997). K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature, 387, 869–875.PubMedCrossRefGoogle Scholar
  12. Ito, H., & Schuman, E. M. (2009). Distance-dependent homeostatic synaptic scaling mediated by A-type potassium channels. Frontiers in Cellular Neuroscience, 3, 1–15.CrossRefGoogle Scholar
  13. Jiang, L., Sun, S., Nedergaard, M., & Kang, J. (2000). Paired pulse modulation at individual GABAergic synapses in rat hippocampus. Journal of Physiology, 523.2, 425–439.CrossRefGoogle Scholar
  14. Koch, C. (1999). Biophysics of computation: Information processing in single neurons. New York: Oxford University Press.Google Scholar
  15. Magee, J. C. (1998). Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons. Journal of Neuroscience, 18, 7613–7824.PubMedGoogle Scholar
  16. Marasco, A., & Romano, A. (2001). Scientific computing with mathematica: Mathematical problems for ordinary differential equations. Boston: Birkhauser. ISBN 0-8176-4205-6.Google Scholar
  17. Marie, H., Morishita, W., Yu, X., Calakos, N., & Malenka, R. C. (2005). Generation of silent synapses by acute in vivo expression of CaMKIV and CREB. Neuron, 45, 741–752.PubMedCrossRefGoogle Scholar
  18. McCormick, D. A., & Contreras, D. (2001). On the cellular and network bases of epileptic seizures. Annual Review of Physiology, 63, 815–846.PubMedCrossRefGoogle Scholar
  19. Megias, M., Emri, Z., Freund, T. F., & Gulyás, A. I. (2001). Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience, 102, 527–540.PubMedCrossRefGoogle Scholar
  20. Meng, X., Lu, Q., & Rinzel, J. (2011). Control of firing patterns by two transient potassium currents: Leading spike, latency, bistability. Journal of Computational Neuroscience, 31, 117–136.PubMedCrossRefGoogle Scholar
  21. Migliore, M. (1996). Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons. Biophysical Journal, 71, 2394–2403.PubMedCrossRefGoogle Scholar
  22. Migliore, M., Hoffman, D., Magee, J., & Johnston D. (1999). Role of an A-type K  +  conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. Journal of Computational Neuroscience, 7, 5–15.PubMedCrossRefGoogle Scholar
  23. Migliore, M., & Shepherd, G. M. (2002). Emerging rules for the distributions of active dendritic conductances. Nature Reviews. Neuroscience, 3, 362–370.PubMedCrossRefGoogle Scholar
  24. Migliore, M., & Shepherd, G. M. (2005). Opinion: An integrated approach to classifying neuronal phenotypes. Nature Reviews. Neuroscience, 6, 810–818.PubMedCrossRefGoogle Scholar
  25. Moczydlowski, E., & Latorre, R. (1983). Gating kinetics of 2 + -activated K  +  channels from rat muscle incorporated into planar lipid bilayers. Journal of General Physiology, 82, 511–542.PubMedCrossRefGoogle Scholar
  26. Nowacki, J., Osinga, H. M., Browna, J. T., Randall, A. D., & Tsaneva-Atanasova, K. (2011). A unified model of CA1/3 pyramidal cells: An investigation into excitability. Progress in Biophysics and Molecular Biology, 105, 34–48.PubMedCrossRefGoogle Scholar
  27. Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1, 39.PubMedCrossRefGoogle Scholar
  28. Poirazi, P., Brannon, T., & Mel, B. W. (2003). Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron, 37, 977–987.PubMedCrossRefGoogle Scholar
  29. Poirazi, P., Brannon, T., & Mel, B. W. (2003). Pyramidal neuron as 2-layer neural network. Neuron, 37, 989–999.PubMedCrossRefGoogle Scholar
  30. Pospischil, M., Toledo-Rodriguez, M., Monier, C., Piwkowska, Z., Bal, T., Frégnac, Y., et al. (2008). Minimal Hodgkin–Huxley type models for different classes of cortical and thalamic neurons. Biological Cybernetics, 99, 427–441.PubMedCrossRefGoogle Scholar
  31. Remy, S., Beck, H., & Yaari, Y. (2010). Plasticity of voltage-gated ion channels in pyramidal cell dendrites. Current Opinion in Neurobiology, 20, 503–509.PubMedCrossRefGoogle Scholar
  32. Rüdiger, S. (2010). Practical bifurcation and stability analysis practical bifurcation and stability analysis. In Springer series: Interdisciplinary applied mathematics (Vol. 5, 3rd ed.). New York: Springer.Google Scholar
  33. Samsonovich, A. V., & Ascoli, G. A. (2005). Statistical determinants of dendritic morphology in hippocampal pyramidal neurons: A hidden Markov model. Hippocampus, 15, 166–183.PubMedCrossRefGoogle Scholar
  34. Scorza, C. A., Araujo, B. H., Leite, L. A., Torres, L. B., Otalora, L. F., Oliveira, M. S., et al. (2011). Morphological and electrophysiological properties of pyramidal-like neurons in the stratum oriens of Cornu ammonis 1 and Cornu ammonis 2 area of Proechimys. Neuroscience, 177, 252–268.PubMedCrossRefGoogle Scholar
  35. Shah, M. M., Migliore, M., Valencia, I., Cooper, E. C., & Brown, D. A. (2008). Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proceedings of the National Academy of Sciences of the United States of America, 105, 7869–7874.PubMedCrossRefGoogle Scholar
  36. Spruston, N., Schiller, Y., Stuart, G., & Sakmann, B. (1995). Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science, 268, 297–300.PubMedCrossRefGoogle Scholar
  37. Traub, R. D., & Wong, R. K. (1982). Cellular mechanism of neuronal synchronization in epilepsy. Science, 216, 745–747.PubMedCrossRefGoogle Scholar
  38. Traub, R. D., Wong, R. K., Miles, R., & Michelson, H. (1991). A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. Journal of Neurophysiology, 66, 635–650.PubMedGoogle Scholar
  39. Troy, W. C. (1974). Oscillatory phenomena in nerve conduction equations. Ph.D. dissertation, SUNY at Buffalo.Google Scholar
  40. Troy, W. C. (1978). The bifurcation of periodic solutions in the Hodgkin–Huxley equations. Quarterly of Applied Mathematics, 36, 73–83.Google Scholar
  41. Xiong, W., & Chen, W. R. (2002). Dynamic gating of spike propagation in the mitral cell lateral dendrites. Neuron, 34, 115–126.PubMedCrossRefGoogle Scholar
  42. Zemankovics, R., Káli, S., Paulsen, O., Freund, T. F., & Hájos, N. (2010). Differences in subthreshold resonance of hippocampal pyramidal cells and interneurons: The role of h-current and passive membrane characteristics. Journal of Physiology, 588(12), 2109–2132.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Daniela Bianchi
    • 1
  • Addolorata Marasco
    • 2
  • Alessandro Limongiello
    • 2
  • Cristina Marchetti
    • 3
  • Helene Marie
    • 3
    • 4
  • Brunello Tirozzi
    • 1
  • Michele Migliore
    • 5
  1. 1.Department of PhysicsUniversity of Rome “La Sapienza”RomeItaly
  2. 2.Department of Mathematics and Applications “R. Caccioppoli”University of Naples Federico IINaplesItaly
  3. 3.European Brain Research Institute “Rita Levi-Montalcini”RomeItaly
  4. 4.IPMC - CNRS UMR6097ValbonneFrance
  5. 5.Institute of Biophysics National Research CouncilPalermoItaly

Personalised recommendations