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A hemicord locomotor network of excitatory interneurons: a simulation study

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Abstract

Locomotor burst generation is simulated using a full-scale network model of the unilateral excitatory interneuronal population. Earlier small-scale models predicted that a population of excitatory neurons would be sufficient to produce burst activity, and this has recently been experimentally confirmed. Here we simulate the hemicord activity induced under various experimental conditions, including pharmacological activation by NMDA and AMPA as well as electrical stimulation. The model network comprises a realistic number of cells and synaptic connectivity patterns. Using similar distributions of cellular and synaptic parameters, as have been estimated experimentally, a large variation in dynamic characteristics like firing rates, burst, and cycle durations were seen in single cells. On the network level an overall rhythm was generated because the synaptic interactions cause partial synchronization within the population. This network rhythm not only emerged despite the distributed cellular parameters but relied on this variability, in particular, in reproducing variations of the activity during the cycle and showing recruitment in interneuronal populations. A slow rhythm (0.4–2 Hz) can be induced by tonic activation of NMDA-sensitive channels, which are voltage dependent and generate depolarizing plateaus. The rhythm emerges through a synchronization of bursts of the individual neurons. A fast rhythm (4–12 Hz), induced by AMPA, relies on spike synchronization within the population, and each burst is composed of single spikes produced by different neurons. The dynamic range of the fast rhythm is limited by the ability of the network to synchronize oscillations and depends on the strength of synaptic connections and the duration of the slow after hyperpolarization. The model network also produces prolonged bouts of rhythmic activity in response to brief electrical activations, as seen experimentally. The mutual excitation can sustain long-lasting activity for a realistic set of synaptic parameters. The bout duration depends on the strength of excitatory synaptic connections, the level of persistent depolarization, and the influx of Ca2+ ions and activation of Ca2+-dependent K+ current.

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References

  • Alford S, Williams TL (1989) Endogenous activation of glycine and NMDA receptors in lamprey spinal cord during fictive locomotion. J Neurosci 9(8):2792–2800

    PubMed  CAS  Google Scholar 

  • Aoki F, Wannier T, Grillner S (2001) Slow dorsal–ventral rhythm generator in the lamprey spinal cord. J Neurophysiol 85(1):211–218

    PubMed  CAS  Google Scholar 

  • Ben-Ari Y (2001) Developing networks play a similar melody. TINS 24(6):353–360

    PubMed  CAS  Google Scholar 

  • Bower JM, Beeman D (1998) The book of GENESIS exploring realistic neural models with the GEneral NEural SImulation System, 2nd edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Bracci E, Ballerini L, Nistri A (1996) Localization of rhythmogenic networks responsible for spontaneous bursts induced by strychnine and bicuculine in the rat isolated spinal cord. J Neurosci 16(21):7063–7076

    PubMed  CAS  Google Scholar 

  • Brodin L, Tråven HG, Lansner A, Wallén P, Ekeberg Ö, Grillner S (1991) Computer simulations of N-methyl-d-aspartate receptor-induced membrane properties in a neuron model. J Neurophysiol 66(2):473–484

    PubMed  CAS  Google Scholar 

  • Buchanan JT (1993) Electrophysiological properties of identified classes of lamprey spinal neurons. J Neurophysiol 70(6):2313–2325

    PubMed  CAS  Google Scholar 

  • Buchanan JT (1999) Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. J Neurophysiol 81(5):2037–2045

    PubMed  CAS  Google Scholar 

  • Buchanan JT (2001) Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology. Prog Neurobiol 63:441–466

    Article  PubMed  CAS  Google Scholar 

  • Buchanan JT, Brodin L, Dale N, Grillner S (1987) Reticulospinal neurones activate excitatory amino acid receptors. Brain Res 408(1–2):321–325

    Article  PubMed  CAS  Google Scholar 

  • Buchanan JT, Grillner S, Cullheim S, Risling M (1989) Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function. J Neurophysiol 62(1):59–69

    PubMed  CAS  Google Scholar 

  • Cangiano L (2004) Mechanisms of rhythm generation in the lamprey locomotor network. PhD Thesis, Karolinska Institute, Stockholm

  • Cangiano L, Grillner S (2003) Fast and slow locomotor burst generation in the hemispinal cord of the lamprey. J Neurophysiol 89:2931–2942

    Article  PubMed  CAS  Google Scholar 

  • Cangiano L, Grillner S (2005) Mechanisms of rhythm generation in a spinal locomotor network deprived of crossed connections: the lamprey hemicord. J Neurosci 25(4):923–935

    Article  PubMed  CAS  Google Scholar 

  • Cohen AH, Harris-Warrick RM (1984) Strychnine eliminates alternating motor output during fictive locomotion in the lamprey. Brain Res 293(1):164–167

    Article  PubMed  CAS  Google Scholar 

  • Cohen AH, Wallén P (1980) The neuronal correlate of locomotion in fish. “Fictive swimming” induced in an in vitro preparation of the lamprey spinal cord. Exp Brain Res 41(1):11–18

    Article  PubMed  CAS  Google Scholar 

  • Dale N (1986) Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey. J Neurosci 6(9):2662–2675

    PubMed  CAS  Google Scholar 

  • Dale N, Grillner S (1986) Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors. J Neurosci 6(9):2653–2661

    PubMed  CAS  Google Scholar 

  • Ekeberg Ö, Wallén P, Lansner A, Tråven H, Brodin L, Grillner S (1991) A computer based model for realistic simulations of neural networks. I. The single neuron and synaptic interaction. Biol Cybern 65(2):81–90

    Article  PubMed  CAS  Google Scholar 

  • Grillner S (2003) The motor infrastructure: from ion channels to neuronal networks. Nat Rev Neurosci 4(7):573–586

    Article  PubMed  CAS  Google Scholar 

  • Grillner S, Brodin L, Sigvardt K, Dale N (1986) On the spinal network generating locomotion in lamprey: transmitters, membrane properties and circuitry. In: Grillner S, Stein PSG, Stuart DG, Frossberg H, Herman RM (eds) Neurobiology of Vertebrate Locomotion. Wenner-Gren Center international symposium series, vol 45. Macmillan, London, pp 335–352

    Google Scholar 

  • Hagevik A, McClellan AD (1994) Coupling of spinal locomotor networks in larval lamprey revealed by receptor blockers for inhibitory amino acids: neurophysiology and computer modeling. J Neurophysiol 72(4):1810–1829

    PubMed  CAS  Google Scholar 

  • Hammarlund P (1996) Techniques for efficient parallel scientific computing. PhD Thesis, Royal Institute of Technology, Stockholm

  • Hammarlund P, Ekeberg Ö (1998) Large neural network simulations on multiple hardware platforms. J Comput Neurosci 5(4):443–59

    Article  PubMed  CAS  Google Scholar 

  • Hellgren J, Grillner S, Lansner A (1992) Computer simulation of the segmental neural network generating locomotion in lamprey by using populations of network interneurons. Biol Cybern 68(1):1–13

    Article  PubMed  CAS  Google Scholar 

  • Kiemel T, Gormley KM, Guan L, Williams TL, Cohen AH (2003) Estimating the strength and direction of functional coupling in the lamprey spinal cord. J Comput Neurosci 15(2):233–245

    Article  PubMed  Google Scholar 

  • Kettunen P, Hess D, El Manira A (2003) mGluR1, but not mGluR5, mediates depolarization of spinal cord neurons by blocking a leak current. J Neurophysiol 90(4):2341–2348

    Article  PubMed  CAS  Google Scholar 

  • Kotaleski JH, Grillner S, Lansner A (1999a) Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey. I. Segmental oscillations dependent on reciprocal inhibition. Biol Cybern 81(4):317–330

    Article  PubMed  CAS  Google Scholar 

  • Kotaleski JH, Lansner A, Grillner S (1999b) Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey. II. Hemisegmental oscillations produced by mutually coupled excitatory neurons. Biol Cybern 81(4):299–315

    Article  PubMed  CAS  Google Scholar 

  • Kozlov A, Kotaleski JH, Aurell E, Grillner S, Lansner A (2001) Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation. J Comput Neurosci 11(2):183–200

    Article  PubMed  CAS  Google Scholar 

  • Kozlov AK, Ullén F, Fagerstedt P, Aurell E, Lansner A, Grillner S (2002) Mechanisms for lateral turns in lamprey in response to descending unilateral commands: a modeling study. Biol Cybern 86(1):1–14

    Article  PubMed  Google Scholar 

  • Kozlov AK, Kotaleski JH, Wallén P, Grillner S, Lansner A (2003) Detailed and reduced models of the excitatory hemi-cord locomotor network in lamprey. Soc Neurosci Abstract 278.5

  • Lansner A, Ekeberg Ö, Grillner S (1997a) Realistic modeling of burst generation and swimming in lamprey. In: Stein PSG, Grillner S, Selverston AI, Stuart DG (eds) Neurons, networks, and motor behavior. MIT Press, Tucson, pp 165–171

    Google Scholar 

  • Lansner A, Hellgren Kotaleski J, Ullström M, Grillner S (1997b) Local spinal modulation of the calcium dependent potassium channel underlying slow adaptation in a model of the lamprey CPG. In: Bower JM (eds) Computational neuroscience: trends in research. Plenum, Big Sky, Oxford, pp 429–434

    Google Scholar 

  • Lansner A, Kotaleski JH, Grillner S (1998) Modeling of the spinal neuronal circuitry underlying locomotion in a lower vertebrate. Ann NY Acad Sci 860:239–249

    Article  PubMed  CAS  Google Scholar 

  • Marchetti C, Tabak J, Chub N, O’Donovan MJ, Rinzel J (2005) Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride. J Neurosci 25(14):3601–3612

    Article  PubMed  CAS  Google Scholar 

  • Ohta Y, Grillner S (1989) Monosynaptic excitatory amino acid transmission from the posterior rhombencephalic reticular nucleus to spinal neurons involved in the control of locomotion in lamprey. J Neurophysiol 62(5):1079–1089

    PubMed  CAS  Google Scholar 

  • Parker D (2003) Variable properties in a single class of excitatory spinal synapse. J Neurosci 23(8):3154–3163

    PubMed  CAS  Google Scholar 

  • Parker D, Grillner S (2000) The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord. Eur J Neurosci 12(6):2135–2146

    Article  PubMed  CAS  Google Scholar 

  • Rovainen CM (1974) Synaptic interactions of reticulospinal neurons and nerve cells in the spinal cord of the sea lamprey. J Comp Neurol 154(2):207–223

    Article  PubMed  CAS  Google Scholar 

  • Roberts A, Tunstall MJ (1990) Mutual re-excitation with post-inhibitory rebound: a simulation study on the mechanisms for locomotor rhythm generation in the spinal cord of Xenopus embryos. Eur J Neurosci 2(1):11–23

    Article  PubMed  Google Scholar 

  • Sillar KT, Roberts A (1993) Control of frequency during swimming in Xenopus embryos: a study on interneuronal recruitment in a spinal rhythm generator. J Physiol 472:557–572

    PubMed  CAS  Google Scholar 

  • Tabak J, Senn W, O’Donovan MJ, Rinzel J (2000) Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network. J Neurosci 20(8):3041–3056

    PubMed  CAS  Google Scholar 

  • Tegnér J, Kotaleski JH, Lansner A, Grillner S (1997) Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment. J Neurophysiol 77(4):1795–1812

    PubMed  Google Scholar 

  • Tråven HG, Brodin L, Lansner A, Ekeberg Ö, Wallén P, Grillner S (1993) Computer simulations of NMDA and non-NMDA receptor-mediated synaptic drive: sensory and supraspinal modulation of neurons and small networks. J Neurophysiol 70(2):695–709

    PubMed  Google Scholar 

  • Ullström M, Kotaleski JH, Tegnér J, Aurell E, Grillner S, Lansner A (1998) Activity-dependent modulation of adaptation produces a constant burst proportion in a model of the lamprey spinal locomotor generator. Biol Cybern 79(1):1–14

    Article  PubMed  Google Scholar 

  • Wadden T, Hellgren J, Lansner A, Grillner S (1997) Intersegmental coordination in the lamprey: simulations using a network model without segmental boundaries. Biol Cybern 76(1):1–9

    Article  Google Scholar 

  • Wallén P, Grafe P, Grillner S (1984) Phasic variations of extracellular potassium during fictive swimming in the lamprey spinal cord in vitro. Acta Physiol Scand 120(3):457–463

    Article  PubMed  Google Scholar 

  • Wallén P, Ekeberg Ö, Lansner A, Brodin L, Tråven H, Grillner S (1992) A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey. J Neurophysiol 68(6):1939–1950

    PubMed  Google Scholar 

  • Wolf E, Roberts A (1995) The influence of premotor interneuron populations on the frequency of the spinal pattern generator for swimming in Xenopus embryos: a simulation study. Eur J Neurosci 7(4):671–678

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

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

    A. K. Kozlov, A. Lansner & J. Hellgren Kotaleski

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

    A. K. Kozlov, S. Grillner & J. Hellgren Kotaleski

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  1. A. K. Kozlov
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  2. A. Lansner
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  3. S. Grillner
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  4. J. Hellgren Kotaleski
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Correspondence to A. K. Kozlov.

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Kozlov, A.K., Lansner, A., Grillner, S. et al. A hemicord locomotor network of excitatory interneurons: a simulation study. Biol Cybern 96, 229–243 (2007). https://doi.org/10.1007/s00422-006-0132-2

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  • DOI: https://doi.org/10.1007/s00422-006-0132-2

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