Calcium signaling and the development of specific neuronal connections.

During the development of the brain, synaptic connections between nerve cells are being established with remarkable specificity. This is achieved by a series of steps: first, axons grow to their terminal areas. Second, axons and dendrites contact each other and select among potential synaptic partners. Third, after synapses have become functional, the fine-tuning of synaptic connections optimizes emerging networks to perform their specific functions. Here, I summarize the evidence for a central role of intracellular calcium signaling in all three stages of the development of specific synaptic connections. In particular, calcium signaling has the capacity to integrate information from a wide array of extracellular factors that are known to regulate neuronal development, such as molecular cues or neuronal activity. Calcium signaling, in turn, directs structural as well as functional adaptations in individual neurons that underlie the establishment of synaptic specificity. Importantly, evidence is accumulating that errors in calcium-dependent network maturation are associated with neurodevelopmental disorders. Therefore, understanding the role of calcium in setting up brain networks may not only advance our insights into mechanisms of normal brain development, but also help identifying the causes of diseases such as autism or mental retardation.