Increasing the Frequency of Spontaneous Rhythmic Activity Disrupts Pool-Specific Axon Fasciculation and Pathfinding of Embryonic Spinal Motoneurons

Abstract

Rhythmic spontaneous bursting activity, which occurs in many developing neural circuits, has been considered to be important for the refinement of neural projections but not for early pathfinding decisions. However, the precise frequency of bursting activity differentially affects the two major pathfinding decisions made by chick lumbosacral motoneurons. Moderate slowing of burst frequency was shown previously to cause motoneurons to make dorsoventral (D-V) pathfinding errors and to alter the expression of molecules involved in that decision. Moderate speeding up of activity is shown here not to affect these molecules or D-V pathfinding but to strongly perturb the anteroposterior (A-P) pathfinding process by which motoneurons fasciculate into pool-specific fascicles at the limb base and then selectively grow to muscle targets. Resumption of normal frequency allowed axons to correct the A-P pathfinding errors by altering their trajectories distally, indicating the dynamic nature of this process and its continued sensitivity to patterned activity.