title: Fast regulation of axonal growth cone motility by electrical activity.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, Bordeaux Neuroscience Institute, Université Bordeaux 2, 33077 Bordeaux, France.
authors.forename: Gaskon
authors.initials: G
authors.lastname: Ibarretxe
authors.forename: David
authors.initials: D
authors.lastname: Perrais
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jaskolski
authors.forename: Alice
authors.initials: A
authors.lastname: Vimeney
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000648:ultrastructure*; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020439:Growth Cones / Q000502:physiology* / Q000528:radiation effects*; D006624:Hippocampus / Q000166:cytology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology; D017470:Receptors, Glutamate / Q000172:deficiency; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D001569:Benzodiazepines; C079692:GYKI 53655; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid; D002118:Calcium