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This article is part of the supplement: Twenty First Annual Computational Neuroscience Meeting: CNS*2012

Open Access Poster presentation

Modeling [Ca2+]o- and [K+]o-dependent oscillations in spinal Hb9 interneurons

Natalia A Shevtsova1*, Sabrina Tazerart23, Laurent Vinay2, Frédéric Brocard2 and Ilya A Rybak1

Author Affiliations

1 Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA

2 Institut de Neurosciences de la Timone (UMR7289), CNRS and Aix-Marseille Université, Marseille 13385, France

3 Departments of Surgery and Anatomy and Neurobiology, Dalhousie University, Halifax NS B3H 3A7, Canada

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BMC Neuroscience 2012, 13(Suppl 1):P49  doi:10.1186/1471-2202-13-S1-P49


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/13/S1/P49


Published:16 July 2012

© 2012 Shevtsova et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Poster presentation

The spinal interneurons in newborn rodents, when synaptically isolated by removing the extracellular calcium ([Ca2+]o), demonstrate intrinsic rhythmic bursting activity that can be suppressed by riluzole, a blocker of the persistent sodium current (INaP) [2]. This finding led to the suggestion that lowering of [Ca2+]o may enhance INaP by shifting its activation threshold toward more negative voltages, and raised the question of functional relevance of this finding to generation of locomotor rhythm. To assess this issue, a series of experiments was performed in vitro using the isolated spinal cord preparation from the neonatal rat with measurements of [Ca2+]o and extracellular potassium concentration ([K+]o) during pharmacologically induced fictive locomotion. We demonstrated that with the onset of fictive locomotion, [Ca2+]o reduced from 1.2 up to 0.9 mM whereas [K+]o increased from 4 up to 6 mM. At the same time, a special study performed on the isolated genetically identified Hb9 excitatory interneurons showed that, at [Ca2+]o= 1 mM and [K+]o=5 mM, 12% of Hb9 cells expressed intrinsic INaP-dependent bursting, and at the concentrations typical for fictive locomotion ([Ca2+]o= 0.9 mM and [K+]o=6 mM), as many as 50% of identified Hb9 interneurons expressed INaP-dependent bursting. Importantly, the threshold of [Ca2+]o to generate bursting decreased as [K+]o increased. The analysis of Hb9 neuron behavior during slow ramp increase of voltage revealed that lowering [Ca2+]o from 1.2 to 0.9 mM induced a negative shift (~ -3 mV) in the INaP half-activation voltage (V1/2NaP). In contrast, V1/2NaP was not changed when [K+]o increased from 4 to 6 mM.

To theoretically investigate the effect of changing [Ca2+]o and [K+]o on the Hb9’s pacemaker properties and firing behavior, we developed a single-compartment computational model of Hb9 neuron. In this model, we explicitly simulated a negative shift of V1/2NaP occurring with the reduction of [Ca2+]o.. At [K+]o=6 mM, our model exhibited tonic activity at V1/2NaP = –50 mV (Fig. 1A, left). The rhythmic bursting emerged at V1/2NaP = –51 mV, and further shifting V1/2NaP to the left produced stable bursting (Fig. 1A, right). In turn, an increase in [K+]o reduced the potassium reversal potential and hence all voltage-gated potassium currents (IK), which provided an additional augmentation of INaP-dependent bursting [1]. To study a synergistic effect of [Ca2+]o and [K+]oon the emergence of bursting activity, we modeled a population of 50 uncoupled neurons with randomly distributed parameters (see Fig. 1B). Our simulations have shown that shifting V1/2NaP towards more negative values induced by reducing [Ca2+]o may play a major role in emergence of bursting activity in the population of spinal interneurons. We have also demonstrated that accumulation of [K+]ocan facilitate the emergence of INaP-dependent bursting via the reduction of IK.

thumbnailFigure 1. A. Switching from tonic to bursting activity in the modeled neuron by shifting V1/2NaP to more negative value. B. The synergistic effect of [Ca2+]o and [K+]ochanges on emergence of bursting activity in the modeled population of 50 uncoupled cells.

In summary we suggest that co-regulation of INaP and IK by the corresponding changes in [Ca2+]o and [K+]o may convert activity of spinal interneurons from asynchronous/tonic to the synchronized bursting. This activity-dependent switching in firing behavior may represent a fundamental mechanism for locomotor rhythm generation in the spinal cord.

References

  1. Rybak IA, Shevtsova NA, St-John WM, Paton JFR, Pierrefiche O: Endogenous rhythm generation in the pre-Bötzinger complex and ionic currents: modelling and in vitro studies.

    Eur J Neurosci 2003, 18:239-257. PubMed Abstract | Publisher Full Text OpenURL

  2. Tazerart S, Vinay L, Brocard F: The persistent sodium current generates pacemaker activities in the central pattern generator for locomotion and regulates the locomotor rhythm.

    J Neurosci 2008, 28:8577-8589. PubMed Abstract | Publisher Full Text OpenURL