Activity-dependent neuronal differentiation prior to synapse formation: the functions of calcium transients.

Spinal cord neurons become excitable prior to synapse formation, and generate spontaneous calcium transients that regulate aspects of their differentiation before neuronal networks are established. Calcium spikes, generated by calcium-dependent action potentials and calcium-induced calcium release (CICR), regulate transcription. Growth cone calcium transients, produced by calcium influx through unidentified channels that triggers CICR, control the rate of axon outgrowth in response to environmental cues. Filopodial calcium transients, generated by calcium influx through channels activated by beta1 integrins, signal information about the molecular identity of the substrate and regulate growth cone turning. All three classes of calcium transients appear to use a frequency code to implement their effects. Oscillations of second messengers in embryonic neurons and perhaps more generally in other differentiating cells may behave like a kinetic quilt, demonstrating patchy fluctuations in concentrations that orchestrate the complex processes of development.