Local Calcium Signalling by Inositol-1,4,5-trisphosphate in Purkinje Cell Dendrites

The second messenger inositol-1,4,5-trisphosphate (InsP3) releases Ca2+ from intracellular Ca2+ stores by activating specific receptors on the membranes of these stores. In many cells, InsP3 is a global signalling molecule that liberates Ca2+ throughout the cytoplasm. However, in neurons the situation might be different, because synaptic activity may produce InsP3 at discrete locations. Here we characterize InsP3 signalling in postsynaptic cerebellar Purkinje neurons, which have a high level of InsP3 receptors. We find that repetitive activation of the synapse between parallel fibres and Purkinje cells causes InsP3-mediated Ca2+ release in the Purkinje cells. This Ca2+ release is restricted to individual postsynaptic spines, where both metabotropic glutamate receptors and InsP3 receptors are located, or to multiple spines and adjacent dendritic shafts. Focal photolysis of caged InsP3 in Purkinje cell dendrites also produces Ca2+ signals that spread only a few micrometres from the site of InsP3 production. Uncaged InsP3 produces a long-lasting depression of parallel-fibre synaptic transmission that is limited to synapses where the Ca2+ concentration is raised. Thus, in Purkinje cells InP3 acts within a restricted spatial range that allows it to regulate the function of local groups of parallel-fibre synapses.