Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.

TitleActivity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.
Publication TypeJournal Article
Year of Publication2013
AuthorsPlazas PV, Nicol X, Spitzer NC
JournalProc Natl Acad Sci U S A
Volume110
Issue4
Pagination1524-9
Date Published2013 Jan 22
ISSN1091-6490
KeywordsAnimals, Animals, Genetically Modified, Axons, Calcium Signaling, Gene Knockdown Techniques, Humans, Motor Neurons, Neural Pathways, Potassium Channels, Inwardly Rectifying, Receptors, Cell Surface, Recombinant Proteins, Synaptic Transmission, Zebrafish, Zebrafish Proteins
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.

DOI10.1073/pnas.1213048110
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID23302694
PubMed Central IDPMC3557035
Grant ListNS15818 / NS / NINDS NIH HHS / United States
NS57690 / NS / NINDS NIH HHS / United States
Category: 
Spitzer Laboratory