Skip to main content
Springer Nature Link
Log in

An experimentally constrained computational model of NMDA oscillations in lamprey CPG neurons

  • Published:
Journal of Computational Neuroscience Aims and scope Submit manuscript

Abstract

Rhythmicity is a characteristic of neural networks responsible for locomotion. In many organisms, activation of N-methyl-d-aspartate (NMDA) receptors leads to generation of rhythmic locomotor patterns. In addition, single neurons can display intrinsic, NMDA-dependent membrane potential oscillations when pharmacologically isolated from each other by tetrodotoxin (TTX) application. Such NMDA–TTX oscillations have been characterized, for instance, in lamprey locomotor network neurons. Conceptual and computational models have been put forward to explain the appearance and characteristics of these oscillations. Here, we seek to refine the understanding of NMDA–TTX oscillations by combining new experimental evidence with computational modelling. We find that, in contrast to previous computational predictions, the oscillation frequency tends to increase when the NMDA concentration is increased. We develop a new, minimal computational model which can incorporate this new information. This model is further constrained by another new piece of experimental evidence: that regular-looking NMDA–TTX oscillations can be obtained even after voltage-dependent potassium and high-voltage-activated calcium channels have been pharmacologically blocked. Our model conforms to several experimentally derived criteria that we have set up and is robust to parameter changes, as evaluated through sensitivity analysis. We use the model to re-analyze an old NMDA–TTX oscillation model, and suggest an explanation of why it failed to reproduce the new experimental data that we present here.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Notes

  1. Derived from the experimental part of the present study.

  2. See Grillner and Wallén (1985), Wallén and Grillner (1987), El Manira et al. (1994), Tegnér et al. (1998), Tegnér and Grillner (1999), and the present study.

  3. Wallén and Grillner (1987).

  4. Grillner and Wallén (1985).

Abbreviations

NMDA:

N-methyl-d-aspartate

TTX:

tetrodotoxin

TEA:

tetraethylammonium

AMPA:

alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid

CPG:

central pattern generator

KCa :

calcium-dependent potassium channel

Kv :

voltage-dependent potassium channel

Cav :

voltage-dependent calcium channel

References

  • Ascher, P., & Nowak, L. (1988). The role of divalent cations in the N-methyl-d-aspartate responses of mouse central neurones in culture. Journal of Physiology London, 399, 247–266.

    CAS  Google Scholar 

  • Brodin, L., Tråvén, H. G., Lansner, A., Wallén, P., Ekeberg, Ö., & Grillner, S. (1991). Computer simulations of N-methyl-d-aspartate receptor-induced membrane properties in a neuron model. Journal of Neurophysiology, 66, 473–484.

    PubMed  CAS  Google Scholar 

  • Brodin, L., Grillner, S., & Rovainen, C. M. (1985). N-methyl-d-aspartate (NMDA), kainate and quisqualate receptors and the generation of fictive locomotion in the lamprey spinal cord. Brain Research, 325, 302–306.

    Article  PubMed  CAS  Google Scholar 

  • Büschges, A., Wikström, M. A., Grillner, S., & El Manira, A. (2000). Roles of high-voltage activated calcium channel subtypes in a vertebrate spinal locomotor network. Journal of Neurophysiology, 85, 2758–2766.

    Google Scholar 

  • El Manira, A., & Bussières, N. (1997). Calcium channel subtypes in lamprey sensory and motor neurons. Journal of Neurophysiology, 78, 1334–1340.

    PubMed  Google Scholar 

  • El Manira, A., Tegnér, J., & Grillner, S. (1994). Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey. Journal of Neurophysiology, 72, 1852–1861.

    PubMed  Google Scholar 

  • Ermentrout, B. (2002). Simulating, analyzing and animating dynamical systems: A guide to XPPAUT for researchers and students. Philadelphia: SIAM.

    Google Scholar 

  • Grillner, S., & Wallén, P. (1985). The ionic mechanisms underlying N-methyl-d-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion. Neuroscience Letters, 60, 289–294.

    Article  PubMed  CAS  Google Scholar 

  • Guertin, P. A., & Hounsgaard, J. (1998). Chemical and electrical stimulation induce rhythmic motor activity in an in vitro preparation of the spinal cord from adult turtles. Neuroscience Letters, 245, 5–8.

    Article  PubMed  CAS  Google Scholar 

  • Guertin, P. A., & Hounsgaard, J. (2006). Conditional intrinsic voltage oscillations in mature vertebrate neurons undergo specific changes in culture. Journal of Neurophysiology, 95, 2024–2027.

    Article  PubMed  Google Scholar 

  • Heinrich, R., & Rapoport, T. A. (1974). A linear steady-state treatment of enzymatic chains. Critique of the crossover theorem and a general procedure to identify interaction sites with an effector. European Journal of Biochemistry, 42, 97–105.

    Article  CAS  PubMed  Google Scholar 

  • Hess, D., Nanou, E., & El Manira, A. (2007). Characterization of Na+-activated K+ currents in larval lamprey spinal cord neurons. Journal of Neurophysiology, 97, 3484–3493.

    Article  PubMed  CAS  Google Scholar 

  • Huss, M., Lansner, A., Wallén, P., El Manira, A., Grillner, S., & Hellgren Kotaleski, J. (2007). Roles of ionic currents in lamprey CPG neurons: A modeling study. Journal of Neurophysiology, 97, 2696–2711.

    Article  PubMed  CAS  Google Scholar 

  • Kahn, J. A. (1982). Patterns of synaptic inhibition in motoneurons and interneurons during fictive swimming in the lamprey, as revealed by Cl − injections. Journal of Comparative Physiology, 147, 189–194.

    Article  Google Scholar 

  • Kozlov, A., Hellgren Kotaleski, J., Aurell, E., Grillner, S., & Lansner, A. (2001) Modeling of substace P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: Consequences for network pattern generation. Journal of Computational Neuroscience, 11, 183–200.

    Article  PubMed  CAS  Google Scholar 

  • Ingalls, B. P. (2004). Autonomously oscillating biochemical systems: Parametric sensitivity of extrema and period. IEE Systems Biology, 1, 62–70.

    Article  CAS  PubMed  Google Scholar 

  • MacLean, J. N., Schmidt, B. J., Hochman, S. (1997). NMDA receptor activation triggers voltage oscillations, plateau potentials and bursting in neonatal rat lumbar motoneurons in vitro. European Journal of Neuroscience, 9, 2702–2711.

    Article  PubMed  CAS  Google Scholar 

  • Moore, L., & Buchanan, J. (1993). The effects of neurotransmitters on the integrative properties of spinal neurons in the lamprey. Journal of Experimental Biology, 175, 89–114.

    PubMed  CAS  Google Scholar 

  • Nowak, L., Bregestovski, P., Ascher, P., Herbet, P., & Prochiantz, A. (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature, 307, 462–465.

    Article  PubMed  CAS  Google Scholar 

  • Russell, D. F., & Wallén, P. (1983). On the control of myotomal motoneurones during “fictive swimming” in the lamprey spinal cord in vitro. Acta Physiologica Scandinavica, 117, 161–170.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, H., & Jirstrand, M. (2006). Systems biology toolbox for MATLAB: A computational platform for research in systems biology. Bioinformatics, 22, 514–515.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, B. J., Hochman, S., & MacLean, J. N. (1998). NMDA receptor-mediated oscillatory properties: Potential role in rhythm generation in the mammalian spinal cord. Annals of the New York Academy of Sciences, 860, 189–202.

    Article  PubMed  CAS  Google Scholar 

  • Sillar, K. T., & Simmers, A. J. (1994). 5-HT induces NMDA receptor-mediated intrinsic oscillations in embryonic amphibian spinal neurons. Proceedings of the Royal Society of London Series B Biological Sciences, 255, 139–145.

    Article  CAS  Google Scholar 

  • Tegnér, J., & Grillner S. (1999). Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. Journal of Neurophysiology, 81, 1318–1329.

    PubMed  Google Scholar 

  • Tegnér, J., Lansner, A., & Grillner, S. (1998). Modulation of burst frequency by calcium-dependent potassium channels in the lamprey locomotor system: Dependence of the activity level. Journal of Computational Neuroscience, 5, 121–140.

    Article  PubMed  Google Scholar 

  • Wallén, P., & Grillner, S. (1987). N-methyl-D-aspartate receptorinduced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey. Journal of Neuroscience, 7, 2745–2755.

    PubMed  Google Scholar 

  • Wallén, P., & Williams, T. (1984). Fictive locomotion in the lamprey spinal cord in vitro compared with swimming in the intact and spinal animal. Journal of Physiology, 347, 225–239.

    PubMed  Google Scholar 

  • Wikström, M. A., & El Manira, A. (1998). Calcium influx through N- and P/Q-type channels activate apamin-sensitive calcium-dependent potassium channels generating the late afterhyperpolarization in lamprey spinal neurons. European Journal of Neuroscience, 10, 1528–1532.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

MH was supported by European Commission grant IST-001917 (“Neurobotics”). JHK acknowledges support from the Swedish Research Council. We thank Ebba Samuelsson, Russell Hill, Peter Wallén, Elling Jacobsen, Sten Grillner, Anders Lansner and Pål Westermark for useful discussions.

Author information

Authors and Affiliations

  1. School of Computer Science and Communication, Royal Institute of Technology, 100 44, Stockholm, Sweden

    Mikael Huss & Jeanette Hellgren Kotaleski

  2. Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institutet, 171 77, Stockholm, Sweden

    Mikael Huss, Di Wang, Martin Wikström & Jeanette Hellgren Kotaleski

  3. School of Electrical Engineering, Royal Institute of Technology, 100 44, Stockholm, Sweden

    Camilla Trané

Authors
  1. Mikael Huss
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Di Wang
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Camilla Trané
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Martin Wikström
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Jeanette Hellgren Kotaleski
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Mikael Huss.

Additional information

Action Editor: Christiane Linster

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huss, M., Wang, D., Trané, C. et al. An experimentally constrained computational model of NMDA oscillations in lamprey CPG neurons. J Comput Neurosci 25, 108–121 (2008). https://doi.org/10.1007/s10827-007-0067-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10827-007-0067-1

Keywords