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Alternative pre-mRNA splicing is a common way of gene expression regulation in metazoans. The selective use of specific exons can be modulated in response to various manipulations that alter Ca++ signals, particularly in neurons. A number of splicing factors have also been found to be controlled by Ca++ signals. Moreover, pre-mRNA elements have been identified that are essential and sufficient to mediate Ca++-regulated splicing, providing model systems for dissecting the involved molecular components. In neurons, this regulation likely contributes to the fine-tuning of neuronal properties.