Coincidence detection in single dendritic spines mediated by calcium release

Cerebellar long-term depression (LTD) is a calcium-dependent process in whi ch coincident activity of parallel fiber (PF) and climbing fiber (CF) synap ses causes a long-lasting decrease in PF synaptic strength onto Purkinje ce lls. Here we show that pairing CF activation with bursts of PF activity tri ggers large (>10 muM) calcium signals in Purkinje cell dendrites. When PFs are densely activated, signals span whole dendritic branchlets and are medi ated by voltage-dependent calcium entry. When PFs are sparsely activated, h owever, signals are restricted to single spines and blocked by metabotropic glutamate receptor antagonists. Single-spine signals and sparse-stimulatio n LTD are also blocked by thapsigargin, indicating that calcium must be rel eased from stores. Single-spine signals and sparse-stimulation LTD are grea test when PF activation precedes the CF activation within 50-200 ms. This t iming rule matches the properties of several forms of motor learning, provi ding a link between behavior and functional properties of cerebellar synapt ic plasticity.