Skip to main content
SpringerLink
Log in

Motoneuron model of self-sustained firing after spinal cord injury

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

Abstract

Under many conditions spinal motoneurons produce plateau potentials, resulting in self-sustained firing and providing a mechanism for translating short-lasting synaptic inputs into long-lasting motor output. During the acute-stage of spinal cord injury (SCI), the endogenous ability to generate plateaus is lost; however, during the chronic-stage of SCI, plateau potentials reappear with prolonged self-sustained firing that has been implicated in the development of spasticity. In this work, we extend previous modeling studies to systematically investigate the mechanisms underlying the generation of plateau potentials in motoneurons, including the influences of specific ionic currents, the morphological characteristics of the soma and dendrite, and the interactions between persistent inward currents and synaptic input. In particular, the goal of these computational studies is to explore the possible interactions between morphological and electrophysiological changes that occur after incomplete SCI. Model results predict that some of the morphological changes generally associated with the chronic-stage for some types of spinal cord injuries can cause a decrease in self-sustained firing. This and other computational results presented here suggest that the observed increases in self-sustained firing following some types of SCI may occur mainly due to changes in membrane conductances and changes in synaptic activity, particularly changes in the strength and timing of inhibition.

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

Access this article

Log in via an institution

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
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  • Adams, M. M., & Hicks, A. L. (2005). Spasticity after spinal cord injury. Spinal Cord, 43, 577–586.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, D. J., Gorassini, M. A., Fouad, K., Sanelli, L., Han, Y., & Cheng, J. (1999). Spasticity in rats with sacral spinal cord injury. Journal of Neurotrauma, 16, 69–84.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, D. J., Hultborn, H., Fedirchuk, B., & Gorassini, M. A. (1998). Synaptic activation of plateaus in hindlimb motoneurons of decerebrate cats. Journal of Neurophysiology, 80, 2023–2037.

    PubMed  CAS  Google Scholar 

  • Bennett, D. J., Li, Y., & Siu, M. (2001). Plateau potentials in sacrocaudal motoneurons of chronic spinal rats, recorded in vitro. Journal of Neurophysiology, 86, 1955–1971.

    PubMed  CAS  Google Scholar 

  • Binder, M. D., Heckman, C. J., & Powers, R. K. (1996). The physiological control of motoneuron activity. In L. B. Rowell, & J. T. Shepherd (Eds.), Handbook of physiology, exercise: Regulation and integration of multiple systems (Vol. 12, 1–53). Oxford University Press.

  • Booth, V., & Rinzel, J. (1995). A minimal, compartmental model for dendritic origin of bistability of motoneuron firing patterns. Journal of Computational Neuroscience, 2, 299–312.

    Article  PubMed  CAS  Google Scholar 

  • Booth, V., Rinzel, J., & Kiehn, O. (1997). Compartmental model of vertebrate motoneurons for Ca 2 + -dependent spiking and plateau potentials under pharmacological treatment. Journal of Neurophysiology, 78, 3371–3385.

    PubMed  CAS  Google Scholar 

  • Bose, P., Parmer, R., Reier, P. J., & Thompson, F. J. (2005). Morphological changes of the soleus motoneuron pool in chronic midthoracic contused rats. Experimental Neurology, 191, 13–23.

    Article  PubMed  Google Scholar 

  • Bui, T. V., Grande, G., & Rose, P. K. (2008a). Multiple modes of amplification of synaptic inhibition to motoneurons by persistent inward currents. Journal of Neurophysiology, 99, 571–582.

    Article  PubMed  Google Scholar 

  • Bui, T. V., Grande, G., & Rose, P. K. (2008b). Relative location of inhibitory synapses and persistent inward currents determines the magnitude and mode of synaptic amplification in motoneurons. Journal of Neurophysiology, 99, 583–594.

    Article  PubMed  Google Scholar 

  • Bui, T. V., Ter-Mikaelian, M., Bedrossian, D., & Rose, P. K. (2006). Computational estimation of the distribution of L-type Ca 2 +  channels in motoneurons based on variable threshold of activation of persistent inward currents. Journal of Neurophysiology, 95, 225–241.

    Article  PubMed  CAS  Google Scholar 

  • Cullheim, S., Fleshman, J. W., Glenn, L. L., & Burke, R. E. (1987). Membrane area and dendritic structure in type-identified triceps surae alpha motoneurons. Journal of Comparative Neurology, 255, 68–81.

    Article  PubMed  CAS  Google Scholar 

  • Dhooge, A., Govaerts, W., Kuznetsov, Y. A., & Sautois, B. (2003). Matcont: a MATLAB package for numerical bifurcation analysis of ODEs. ACM Transactions on Mathematical Software, 29(2), 141–164.

    Article  Google Scholar 

  • Eken, T., & Kiehn, O. (1989). Bistable firing properties of soleus motor units in unrestrained rats. Acta Physiologica Scandinavica, 136, 383–394.

    Article  PubMed  CAS  Google Scholar 

  • ElBasiouny, S. M., Bennett, D. J., & Mushahwar, V. K. (2005). Simulation of dendritic Ca v 1.3 channels in cat lumbar motorneurons: Spatial distribution. Journal of Neurophysiology, 94, 3961–3974.

    Article  CAS  Google Scholar 

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

    Book  Google Scholar 

  • Fall, C. P., Marland, E. S., Wagner, J. M., & Tyson, J. J. (2002). Computational cell biology. New York: Springer-Verlag.

    Google Scholar 

  • Finkel, A. S., & Redman, S. J. (1983). The synaptic current evoked in cat spinal motoneurons by impulse in single group Ia axons. Journal of Physiology, 342, 615–632.

    PubMed  CAS  Google Scholar 

  • Fleshman, J. W., Segev, I., & Burke, R. B. (1988). Electrotonic architecture of type-identified α-motoneurons in the cat spinal cord. Journal of Neurophysiology, 60(1), 60–85.

    PubMed  CAS  Google Scholar 

  • Fyffe, R. E. (2001). Spinal motoneurons: Synaptic inputs and receptor organization. In T. C. Cope (Ed.), Motor neurobiology of the spinal cord. NY: CRC.

    Google Scholar 

  • Gazula, V. R., Roberts, M., Luzzio, C., Jawad, A. F., & Kalb, R. G. (2004). Effects of limb exercise after spinal cord injury on motoneuron dendrite structure. Journal of Comparative Neurology, 476, 130–145.

    Google Scholar 

  • Gianano, J. M., York, M. M., Pace, J. A., & Schott, S. (1998). Quality of life: Effect of reduced spasticity from intrathecal baclofen. Journal of Neuroscience Nursing, 30, 47–54.

    Article  Google Scholar 

  • Graham, J., Booth, V., & Jung, R. (2005). Modeling motoneurons after spinal cord injury: Persistent inward currents and plateau potentials. Neurocomputing, 65–66, 719–726.

    Article  Google Scholar 

  • Gutman, A. M. (1991). Bistability of dendrites. International Journal of Neural Systems, 1, 291–304.

    Article  Google Scholar 

  • Harvey, P. J., Li, X., Li, Y., & Bennett, D. J. (2006a). 5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury. Journal of Neurophysiology, 96, 1158–1170.

    Article  PubMed  CAS  Google Scholar 

  • Harvey, P. J., Li, X., Li, Y., & Bennett, D. J. (2006b). Endogenous monoamine receptor activation is essential for enabling persistent sodium currents and repetitive firing in rat spinal motoneurons. Journal of Neurophysiology, 96, 1171– 1186.

    Article  PubMed  CAS  Google Scholar 

  • Harvey, P. J., Li, X., Li, Y., & Bennett, D. J. (2006c). Persistent sodium currents and repetitive firing in motoneurons of the sacrocaudal spinal cord of adult rats. Journal of Neurophysiology, 96, 1141–1157.

    Article  PubMed  CAS  Google Scholar 

  • Heckman, C. J., Gorassini, M. A., & Bennett, D. J. (2005) Persistent inward currents in motoneuron dendrites: Implications for motor output. Muscle Nerve, 31, 135–156.

    Article  CAS  Google Scholar 

  • Heckman, C. J., Johnson, M., Mottram, C., & Schuster, J. (2008). Persistent inward currents in spinal motoneurons and their influence on human motoneuron firing patterns. The Neuroscientist, 14, 264–275.

    Article  PubMed  CAS  Google Scholar 

  • Heckman, C. J., Lee, R. H., & Brownstone, R. M. (2003) Hyperexcitable dendrites in motoneurons and their neuromodulatory control during motor behavior. Trends in Neurosciences, 26, 688–695.

    Article  PubMed  CAS  Google Scholar 

  • Hille, B. (2001), Ion channels of excitable membranes (3rd ed.). Sunderland, MA: Sinauer Associates.

    Google Scholar 

  • Hochman, S., & McCrea, D. A. (1994). Effects of chronic spinalization on ankle extensor motoneurons. II Motoneuron electrical properties. Journal of Neurophysiology, 77, 1468–1479.

    Google Scholar 

  • Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal of Physiology, 4, 500–544.

    Google Scholar 

  • Hounsgaard, J., Hultborn, H., Jesperson, B., & Kiehn, O. (1988a). Bistability of α-motoneurons in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan. Journal of Physiology, 405, 345–367.

    PubMed  CAS  Google Scholar 

  • Hounsgaard, J., Kiehn, O., & Mintz, I. (1988b). Response properties of motoneurons in a slice preparation of the turtle spinal cord. Journal of Physiology, 398, 575–589.

    PubMed  CAS  Google Scholar 

  • Hounsgaard, J., & Kiehn, O. (1989). Serotonin induced bistability of turtle motoneurons caused by nifedipine sensitive calcium plateau potential. Journal of Physiology, 414, 265–282.

    PubMed  CAS  Google Scholar 

  • Hounsgaard, J., & Kiehn, O. (1993). Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro. Journal of Physiology, 468, 245–259.

    PubMed  CAS  Google Scholar 

  • Hultborn, H., Denton, M. E., Wienecke, J., & Nielsen, J. B. (2003). Variable amplification of synaptic input to cat spinal motoneurons by dendritic persistent inward current. Journal of Physiology, 552, 945–952.

    Article  PubMed  CAS  Google Scholar 

  • Hultborn, H., & Kiehn, O. (1992). Neuromodulation of vertebrate motor neuron membrane properties. Current Opinion in Neurobiology, 2, 770–775.

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, D. B., & Carnevale, N. T. (1999). Passive normalization of synaptic integration influenced by dendritic architecture. Journal of Neurophysiology, 82, 3268–3285.

    PubMed  CAS  Google Scholar 

  • Johnston, D., Magee, J. C., Colbert, C. M., & Cristie, B. R. (1997). Active properties of neuronal dendrites. Annual Review of Neuroscience, 19, 165–186.

    Article  Google Scholar 

  • Kitzman, P. (2005). Alteration in axial motoneuronal morphology in the spinal cord injured spastic rat. Experimental Neurology, 192(1), 100–108.

    Article  Google Scholar 

  • Kuo, J. J., Lee, R. H., Johnson, M. D., Heckman, H. M., & Heckman, C. J. (2003). Active dendritic integration of inhibitory synaptic inputs in vivo. Journal of Neurophysiology, 90, 3617–3624.

    Article  PubMed  Google Scholar 

  • Lee, R. H., & Heckman, C. J. (1996). Influence of voltage-sensitive dendritic conductances on bistable firing and effective synaptic current in cat spinal motoneurons in vivo. Journal of Neurophysiology, 76, 2107–2110.

    PubMed  CAS  Google Scholar 

  • Lee, R. H., & Heckman, C. J. (1998a). Bistability in spinal motoneurons in vivo: systematic variations in persistent inward currents. Journal of Neurophysiology, 80, 585–593.

    Google Scholar 

  • Lee, R. H., & Heckman, C. J. (1998b). Bistability in spinal motoneurons in vivo: Systematic variations in rhythmic firing patterns. Journal of Neurophysiology, 80, 572–582.

    PubMed  CAS  Google Scholar 

  • Lee, R. H., & Heckman, C. J. (2000). Adjustable amplification of synaptic input in the dendrites of spinal motoneurons in vivo. Journal of Neuroscience, 20, 6734–6740.

    PubMed  CAS  Google Scholar 

  • Li, X., & Bennett, D. J. (2007). Apamin-sensitive calcium-activated potassium currents (SK) are activated by persistent calcium currents in rat motoneurons. Journal of Neurophysiology, 97, 3314–3330.

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Murray, K., Harvey, P. J., Ballou, E. W., & Bennett, D. J. (2007). Serotonin facilitates a persistent calcium current in motoneurons of rats with and without spinal cord injury. Journal of Neurophysiology, 97, 1236–1246.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., & Bennett, D. J. (2003). Persistent sodium currents and calcium currents cause plateau potentials in motoneurons of chronic spinal rats. Journal of Neurophysiology, 90(2), 857–869.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Gorassini, M. A., & Bennett, D. J. (2004). Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats. Journal of Neurophysiology, 91(2), 767–783.

    Article  PubMed  CAS  Google Scholar 

  • Lynskey, J. V., Belanger, A., & Jung, R. (2008). Activity-dependent plasticity in spinal cord injury. Journal of Rehabilitation Research and Development, 42, 229–240.

    Article  Google Scholar 

  • Mainen, Z. F., & Sejnowski, T. J. (1996). Influence of dendritic structure on firing pattern in model cortical neurons. Nature, 382, 363–366.

    Article  PubMed  CAS  Google Scholar 

  • NINDS-NIH (2009). NINDS-NIH. Spasticity information page. http://www.ninds.nih.gov/disorders/spasticity/spastic%ity.htm.

  • Perrier, J.-F., & Hounsgaard, J. (2003). Ca 2 + -activated nonselective cationic current (I CAN ) in turtle motoneurons. Journal of Neurophysiology, 82, 730–735.

    Google Scholar 

  • Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1, 39–60.

    Article  PubMed  CAS  Google Scholar 

  • Powers, R. K., & Binder, M. D. (2000). Summation of effective synaptic currents and firing rate modulation in cat spinal motoneurons. Journal of Neurophysiology, 83, 483–500.

    PubMed  CAS  Google Scholar 

  • Powers, R. K., & Binder, M. D. (2003). Persistent sodium and calcium currents in rat hypoglossal motoneurons. Journal of Neurophysiology, 89, 615–624.

    Article  PubMed  CAS  Google Scholar 

  • Prather, J. F., Clark, B. D., & Cope, T. C. (2002). Firing rate modulation of motoneurons activated by cutaneous and muscle receptor afferents in the decerebrate cat. Journal of Neurophysiology, 88, 1867–1879.

    PubMed  CAS  Google Scholar 

  • Rall, W. (1967). Distinguishing theoretical synaptic potentials computed for different somadendritic distributions of synaptic input. Journal of Neurophysiology, 30, 1138–1168.

    PubMed  CAS  Google Scholar 

  • Ramer, L. M., Ramer, M. S., & Steeves, J. D. (2005). Setting the stage for functional repair of spinal cord injuries: A cast of thousands. Spinal Cord, 43, 134–161.

    Article  PubMed  CAS  Google Scholar 

  • Schwindt, P. C., & Crill, W. E. (1980). Role of a persistent inward current in motoneuron bursting during spinal seizures. Journal of Neurophysiology, 43, 1296–1318.

    PubMed  CAS  Google Scholar 

  • Schwindt, P. C., & Crill, W. E. (1982). Factors influencing motoneuron rhythmic firing: results from a voltage–clamp study. Journal of Neurophysiology, 48, 875–890.

    PubMed  CAS  Google Scholar 

  • Schwindt, P. C., & Crill, W. E. (1984). Membrane properties of cat spinal motoneurons. In R. Davidoff (Ed.), Handbook of the spinal cord (pp. 199–242). NY: Dekker.

    Google Scholar 

  • Segev, I., Fleshman, J. W., & Burke, R. E. (1990). Computer simulation of Group Ia EPSPs using morphologically realistic models of cat α-motoneurons. Journal of Neurophysiology, 64, 648–660.

    PubMed  CAS  Google Scholar 

  • Segev, I., & London, M. (2000). Untangling dendrites with quantitative models. Science, 290, 744–750.

    Article  PubMed  CAS  Google Scholar 

  • Shapiro, N. P., & Lee, R. H. (2007). Synaptic amplification versus bistability in motoneuron dendritic processing: A top-down modeling approach. Journal of Neurophysiology, 97, 3948–3960.

    Article  PubMed  Google Scholar 

  • Stuart, G. J., & Redman, S. J. (1990). Voltage dependance of Ia reciprocal inhibitory currents in cat spinal motoneurons. Journal of Physiology, 420, 111–125.

    PubMed  CAS  Google Scholar 

  • van Elburg, R. A. J., & van Ooyen, A. (2010). Impact of dendritic size and dendritic topology on burst firing in pyramidal cells. PLoS Computational Biology, 6, e1000781.

    Article  PubMed  Google Scholar 

  • Vieira, M. F., & Kohn, A. F. (2007). Compartmental models of mammalian motoneurons of types S, FR and FF and their computer simulation. Computers in Biology and Medicine, 37, 842–860.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, L., & Krnjevic, K. (1987). Apamin depresses selectively the after-hyperpolarization of cat spinal motoneurons. Neuroscience Letters, 74, 58–62.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Some of the results described here appeared previously in abstract form. Partial support for this work was provided by the National Institutes of Health R01-NS054282 and by the National Science Foundation through NSF IIS 0613404.

Author information

Authors and Affiliations

  1. School of Mathematical and Statistical Sciences, Center for Adaptive Neural Systems, Arizona State University, Tempe, AZ, 85287, USA

    Mini Kurian & Sharon M. Crook

  2. School of Life Sciences, Center for Adaptive Neural Systems, Arizona State University, Tempe, AZ, 85287, USA

    Sharon M. Crook

  3. School of Biological and Health Systems Engineering, Center for Adaptive Neural Systems, Arizona State University, Tempe, AZ, 85287, USA

    Ranu Jung

Authors
  1. Mini Kurian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon M. Crook
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ranu Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharon M. Crook.

Additional information

Action Editor: K. Sigvardt

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kurian, M., Crook, S.M. & Jung, R. Motoneuron model of self-sustained firing after spinal cord injury. J Comput Neurosci 31, 625–645 (2011). https://doi.org/10.1007/s10827-011-0324-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10827-011-0324-1

Keywords

Search

Navigation