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

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 during axon pathfinding in vivo. We found that generate specific patterns of Ca(2+) spikes at different developmental stages. Spikes arose in the distal axon of duanyu1451 and were propagated to the cell body. Suppression of Ca(2+) spiking activity in single duanyu1451 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 duanyu1451 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.

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