title: Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.
abstract: The role of electrical activity in axon guidance has been extensively studied in vitro. To better understand its role in the intact nervous system, we imaged intracellular Ca(2+) in zebrafish primary motor neurons (PMN) during axon pathfinding in vivo. We found that PMN generate specific patterns of Ca(2+) spikes at different developmental stages. Spikes arose in the distal axon of PMN and were propagated to the cell body. Suppression of Ca(2+) spiking activity in single PMN led to stereotyped errors, but silencing all electrical activity had no effect on axon guidance, indicating that an activity-based competition rule regulates this process. This competition was not mediated by synaptic transmission. Combination of PlexinA3 knockdown with suppression of Ca(2+) activity in single PMN produced a synergistic increase in the incidence of pathfinding errors. However, expression of PlexinA3 transcripts was not regulated by activity. Our results provide an in vivo demonstration of the intersection of spontaneous electrical activity with the PlexinA3 guidance molecule receptor in regulation of axon pathfinding.
authors.affiliation: Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093, USA. pvplazas@gmail.com
authors.forename: Paola V
authors.initials: PV
authors.lastname: Plazas
authors.forename: Xavier
authors.initials: X
authors.lastname: Nicol
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D020013:Calcium Signaling; D055785:Gene Knockdown Techniques; D006801:Humans; D009046:Motor Neurons / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C489457:KCNJ2 protein, human; C524494:Plxna3 protein, zebrafish; D024661:Potassium Channels, Inwardly Rectifying; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D029961:Zebrafish Proteins