Electrical activity modulates growth cone guidance by diffusible factors

Brief periods of electrical stimulation of cultured Xenopus spinal neurons resulted in a marked alteration in the turning responses of the growth cone induced by gradients of attractive or repulsive guidance cues. Netrin-1-in duced attraction was enhanced, and the repulsion induced by myelin-associat ed glycoprotein (MAG) or myelin membrane fragments was converted to attract ion. The effect required the presence of extracellular Ca2+ during electric al stimulation and appeared to be mediated by an elevation of both cytoplas mic Ca2+ and cAMP. Thus, electrical activity may influence the axonal path finding of developing neurons, and intermittent electrical stimulation may be effective in promoting nerve regeneration after injury.