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Activity-Dependent Changes in Extracellular Ca2+ and K+ Reveal Pacemakers in the Spinal Locomotor-Related Network
Journal article   Open access   Peer reviewed

Activity-Dependent Changes in Extracellular Ca2+ and K+ Reveal Pacemakers in the Spinal Locomotor-Related Network

Frédéric Brocard, Natalia A Shevtsova, Mouloud Bouhadfane, Sabrina Tazerart, Uwe Heinemann, Ilya A Rybak and Laurent Vinay
Neuron (Cambridge, Mass.), v 77(6), pp 1047-1054
20 Mar 2013
PMID: 23522041
url
https://doi.org/10.1016/j.neuron.2013.01.026View
Published, Version of Record (VoR) Open

Abstract

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 ([Ca2+]o) to 0.9 mM and increases the extracellular potassium ([K+]o) to 6 mM. Such changes in [Ca2+]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 [Ca2+]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 [Ca2+]o and [K+]o. ► Steady-state [Ca2+]o and [K+]o in the locomotor network change during locomotion ► [Ca2+]o and [K+]o start to change before the onset of locomotion ► Changes in [Ca2+]o and [K+]o trigger pacemaker properties in interneurons ► Pacemaker properties result from an upregulation of the persistent sodium current The mechanisms involved in the generation of the locomotor rhythm remain largely unknown. Brocard et al. find that pacemaker interneurons whose properties are switched on and tuned by network activity-dependent changes in extracellular Ca2+ and K+ play a central role.

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