Title | Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Plazas PV, Nicol X, Spitzer NC |
Journal | Proc Natl Acad Sci U S A |
Volume | 110 |
Issue | 4 |
Pagination | 1524-9 |
Date Published | 2013 Jan 22 |
ISSN | 1091-6490 |
Keywords | Animals, 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. |
DOI | 10.1073/pnas.1213048110 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 23302694 |
PubMed Central ID | PMC3557035 |
Grant List | NS15818 / NS / NINDS NIH HHS / United States NS57690 / NS / NINDS NIH HHS / United States |
Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.
Category:
Spitzer Laboratory