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    Activity-dependent changes in extracellular Ca2+ and K+ reveal pacemakers in the spinal locomotor-related network.
    Neuron 2013 Mar;77(6):1047-54
    Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS and Aix-Marseille Université, F-13385 Marseille, France.
    Changes in the extracellular ionic concentrations occur as a natural consequence of firing activity in large populations of neurons. The extent to which these changes alter the properties of individual neurons and the operation of neuronal networks remains unknown. Here, we show that the locomotor-like activity in the isolated neonatal rodent spinal cord reduces the extracellular calcium ([Ca(2+)]o) to 0.9 mM and increases the extracellular potassium ([K(+)]o) to 6 mM. Such changes in [Ca(2+)]o and [K(+)]o trigger pacemaker activities in interneurons considered to be part of the locomotor network. Experimental data and a modeling study show that the emergence of pacemaker properties critically involves a [Ca(2+)]o-dependent activation of the persistent sodium current (INaP). These results support a concept for locomotor rhythm generation in which INaP-dependent pacemaker properties in spinal interneurons are switched on and tuned by activity-dependent changes in [Ca(2+)]o and [K(+)]o.

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    The persistent sodium current generates pacemaker activities in the central pattern generator for locomotion and regulates the locomotor rhythm.
    J Neurosci 2008 Aug;28(34):8577-89
    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.
    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. Read More
    Low-threshold calcium currents contribute to locomotor-like activity in neonatal mice.
    J Neurophysiol 2012 Jan 12;107(1):103-13. Epub 2011 Oct 12.
    Dept. of Neuroscience, Univ. of Minnesota, 321 Church St., Minneapolis, MN 55455, USA.
    In this study, we examined the contribution of a low-threshold calcium current [I(Ca(T))] to locomotor-related activity in the neonatal mouse. Specifically, the role of I(Ca(T)) was studied during chemically induced, locomotor-like activity in the isolated whole cord and in a genetically distinct population of ventromedial spinal interneurons marked by the homeobox gene Hb9. In isolated whole spinal cords, cycle frequency was decreased in the presence of low-threshold calcium channel blockers, which suggests a role for I(Ca(T)) in the network that produces rhythmic, locomotor-like activity. Read More
    Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life.
    J Neurosci 2013 Feb;33(8):3352-62
    Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA.
    Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst firing and are distinguished by a lower "leak" membrane conductance compared with adjacent nonbursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (K(ir)) channels at physiological membrane potentials. Read More
    Properties of a distinct subpopulation of GABAergic commissural interneurons that are part of the locomotor circuitry in the neonatal spinal cord.
    J Neurosci 2011 Mar;31(13):4821-33
    Department of Physiology and Center for Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.
    Commissural inhibitory interneurons (INs) are integral components of the locomotor circuitry that coordinate left-right motor activity during movements. We have shown that GABA-mediated synaptic transmission plays a key role in generating alternating locomotor-like activity in the mouse spinal cord (Hinckley et al., 2005a). Read More