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The Journal of Neuroscience, August 20, 2008, 28(34):8577-8589; doi:10.1523/JNEUROSCI.1437-08.2008

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Behavioral/Systems/Cognitive
The Persistent Sodium Current Generates Pacemaker Activities in the Central Pattern Generator for Locomotion and Regulates the Locomotor Rhythm

Sabrina Tazerart, Laurent Vinay, and Frédéric Brocard

Laboratoire Plasticité et Physio-Pathologie de la Motricité, Unité Mixte de Recherche 6196, Centre National de la Recherche Scientifique, Université Aix-Marseille, F-13402 Marseille Cedex 20, France

Correspondence should be addressed to Dr. Frédéric Brocard, Laboratoire Plasticité et Physio-Pathologie de la Motricité, Unité Mixte de Recherche 6196, Centre National de la Recherche Scientifique, 31 chemin Joseph Aiguier, F-13402 Marseille Cedex 20, France. Email: brocard{at}dpm.cnrs-mrs.fr

Rhythm generation in neuronal networks relies on synaptic interactions and pacemaker properties. Little is known about the contribution of the latter mechanisms to the integrated network activity underlying locomotion in mammals. We tested the hypothesis that the persistent sodium current (I_NaP) is critical in generating locomotion in neonatal rodents using both slice and isolated spinal cord preparations. After removing extracellular calcium, 75% of interneurons in the area of the central pattern generator (CPG) for locomotion exhibited bursting properties and I_NaP was concomitantly upregulated. Putative CPG interneurons such as commissural and Hb9 interneurons also expressed I_NaP-dependent (riluzole-sensitive) bursting properties. Most bursting cells exhibited a pacemaker-like behavior (i.e., burst frequency increased with depolarizing currents). Veratridine upregulated I_NaP, induced riluzole-sensitive bursting properties, and slowed down the locomotor rhythm. This study provides evidence that I_NaP generates pacemaker activities in CPG interneurons and contributes to the regulation of the locomotor activity.

Key words: neonatal rat; spinal cord; locomotion; central pattern generator; rhythm; riluzole

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Received April 4, 2008; revised June 4, 2008; accepted July 2, 2008.

Correspondence should be addressed to Dr. Frédéric Brocard, Laboratoire Plasticité et Physio-Pathologie de la Motricité, Unité Mixte de Recherche 6196, Centre National de la Recherche Scientifique, 31 chemin Joseph Aiguier, F-13402 Marseille Cedex 20, France. Email: brocard{at}dpm.cnrs-mrs.fr

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