Local calcium release in dendritic spines required for long-term synaptic depression

We have used rats and mice with mutations in myosin-Va to evaluate the rang e and function of IP3-mediated Ca2+ signaling in dendritic spines. In these mutants, the endoplasmic reticulum and its attendant IP3 receptors do not enter the postsynaptic spines of parallel fiber synapses on cerebellar Purk inje cells. Long-term synaptic depression (LTD) is absent at the parallel f iber synapses of the mutants, even though the structure and function of the se synapses otherwise appear normal. This loss of LTD is associated with se lective changes in IP3-mediated Ca2+ signaling in spines and can be rescued by photolysis of a caged Ca2+ compound. Our results reveal that IP3 must r elease Ca2+ locally in the dendritic spines to produce LTD and indicate tha t one function of dendritic spines is to target IP3-mediated Ca2+ release t o the proper subcellular domain.