Role of calcium signaling in axon-dendrite interactions during synapse development

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During the development of the nervous system, axons and dendrites establish contacts some of which will be stabilized and mature into synapses, whereas others will be eliminated. Very little is known about the turnover rate of such contacts. Moreover, while it is clear that patterns of neuronal activity shape synaptic connectivity, the specific activity patterns or signaling factors, which determine the fate of a given contact, have not been identified. Dendritic filopodia are neuronal processes that facilitate contact formation with axons. Recently, we were able to show that the growth of filopodia is characteristically correlated with and regulated by dendritic calcium signaling. Now, we have developed new strategies to image axonal and dendritic structure and calcium signaling simultaneously in hippocampal slices from developing rats or mice. We propose experiments, which take advantage of these technical advances to investigate the structural and functional interactions between dendrites and axons that precede synapse formation. We will describe how axons and dendrites initiate contact and determine the turnover rates of contacts. Subsequently, we will investigate whether calcium transients are generated when dendrites and axons form contacts and finally we will determine whether specific patterns of calcium signaling regulate the establishment, maturation, or elimination of synaptogenic contacts. These experiments will help to understand better, how neurons select synaptic partners and establish specific neuronal networks, which underlie the functions of the brain.