The Journal of Neuroscience, July 18, 2007, 27(29):7684-7695; doi:10.1523/JNEUROSCI.1070-07.2007
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Cellular/Molecular
Fast Regulation of Axonal Growth Cone Motility by Electrical Activity
Gaskon Ibarretxe,
David Perrais,
Frédéric Jaskolski,
Alice Vimeney, and
Christophe Mulle
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, Bordeaux Neuroscience Institute, Université Bordeaux 2, 33077 Bordeaux, France
Correspondence should be addressed to Christophe Mulle, Laboratoire Physiologie Cellulaire de la Synapse, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, Bordeaux Neuroscience Institute, Université Bordeaux 2, 146 rue Léo Saignat, 33077 Bordeaux, France. Email: mulle{at}u-bordeaux2.fr
Axonal growth cones are responsible for the correct guidance of developing axons and the establishment of functional neural networks. They are highly motile because of fast and continuous rearrangements of their actin-rich cytoskeleton. Here we have used live imaging of axonal growth cones of hippocampal neurons in culture and quantified their motility with a temporal resolution of 2 s. Using novel methods of analysis of growth cone dynamics, we show that transient activation of kainate receptors by bath-applied kainate induced a fast and reversible growth cone stalling. This effect depends on electrical activity and can be mimicked by the transient discharge of action potentials elicited in the neuron by intracellular current injections at the somatic level through a patch pipette. Growth cone stalling induced by electrical stimulation is mediated by calcium entry from the extracellular medium as well as by calcium release from intracellular stores that define spatially restricted microdomains directly affecting cytoskeletal dynamics. We propose that growth cone motility is dynamically controlled by transient bursts of spontaneous electrical activity, which constitutes a prominent feature of developing neural networks in vivo.
Key words: growth cone; motility; development; kainate receptors; electrical activity; calcium microdomains
Received Sept. 16, 2006;
revised May 29, 2007;
accepted May 30, 2007.
Correspondence should be addressed to Christophe Mulle, Laboratoire Physiologie Cellulaire de la Synapse, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, Bordeaux Neuroscience Institute, Université Bordeaux 2, 146 rue Léo Saignat, 33077 Bordeaux, France. Email: mulle{at}u-bordeaux2.fr
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