Growth factors repair damaged neural circuits by inducing the growth of new branches from the remaining undamaged axons. However, these new branches are disorganized and bind the wrong targets, compromising their function.

Rachel Sherrard's team (B2A) and colleagues show that, following damage to the mouse olivocerebellar pathway, the neurotrophic factor BDNF induces correctly targeted cerebellar reinnervation by the remaining olivocerebellar axons, thereby restoring lost function. The results show that BDNF modulates Pax3 protein expression, which induces an increase in the polysialylated form of the neuronal adhesion molecule (PSA-NCAM) on axonal terminals, and promotes axonal growth and guidance.

These data show that limiting growth promotion to reinnervation neurons alone enables proper axon growth and guidance, and thus accurate neural circuit reconstruction.