Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3

PAOLA V. PLAZAS; XAVIER NICOL; NICHOLAS C. SPITZER

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2012

0027-8424

The role of electrical activity in axon guidance has been extensivelystudied in vitro. To better understand its role in the intact nervoussystem, we imaged intracellular Ca2+ in zebrafish primary motorneurons (PMNs) during axon pathfinding in vivo. We found thatPMNs generate specific patterns of Ca2+ spikes at different developmentalstages. Spikes arose in the distal axon of PMN and werepropagated to the cell body. Suppression of Ca2+ spiking activity insingle PMNs led to stereotyped errors, but silencing all electricalactivity had no effect on axon guidance, indicating that an activitybasedcompetition rule regulates this process. This competition wasnot mediated by synaptic transmission. Combination of PlexinA3knockdown with suppression of Ca2+ activity in single PMNs produceda synergistic increase in the incidence of pathfinding errors.However, expression of PlexinA3 transcripts was not regulatedby activity. Our results provide an in vivo demonstration of theintersection of spontaneous electrical activity with the PlexinA3guidance molecule receptor in regulation of axon pathfinding.