Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites

The second messenger inositol-1,4,5-trisphosphate (InsP 3 ) releases Ca 2+ from intracellular Ca 2+ stores by activating specific receptors on the membranes of these stores 1 . In many cells, InsP 3 is a global signalling molecule that liberates Ca 2+ throughout thecytoplasm 1 , 2 . However, in neurons the situation might be different 3 , 4 , because synaptic activity may produce InsP 3 at discrete locations. Here we characterize InsP 3 signalling in postsynaptic cerebellar Purkinje neurons, which have a high level of InsP 3 receptors 5 . We find that repetitive activation of the synapse between parallel fibres and Purkinje cells causes InsP 3 -mediated Ca 2+ release in the Purkinje cells. This Ca 2+ release is restricted to individual postsynaptic spines, where both metabotropic glutamate receptors 6 , 7 and InsP 3 receptors 5 are located, or to multiple spines and adjacent dendritic shafts. Focal photolysis of caged InsP 3 ( ref. 8 ) in Purkinje cell dendrites also produces Ca 2+ signals that spread only a few micrometres from the site of InsP 3 production. Uncaged InsP 3 produces a long-lasting depression of parallel-fibre synaptic transmission that is limited to synapses where the Ca 2+ concentration is raised. Thus, in Purkinje cells InP 3 acts within a restricted spatial range that allows it to regulate the function of local groups of parallel-fibre synapses.