Spontaneous calcium transients in developing cortical neurons regulate axon outgrowth

Growth cones of cortical axons pause for many hours in preparation for axon branching. They become large and complex compared with small advancing growth cones. We wanted to investigate whether calcium transients regulate the advance of mammalian CNS growth cones. We found that spontaneous calcium transients in developing cortical neurons have characteristic patterns, frequencies, and amplitudes. Importantly, neurons with large paused growth cones exhibit high-frequency spontaneous calcium transients, which are rare in those with small advancing growth cones. The incidence, frequencies, and amplitudes of calcium transients are inversely related to rates of axon outgrowth. The transients are mediated primarily by L-type voltage-gated calcium channels, and silencing them with channel blockers promotes axon outgrowth. Thus calcium transients regulate growth cone advance by direct effects on the growth cone.