Coincidence detection in single dendritic spines mediated by calcium release.
Cerebellar long-term depression (LTD) is a calcium-dependent process in which coincident activity of parallel fiber (PF) and climbing fiber (CF) synapses causes a long-lasting decrease in PF synaptic strength onto Purkinje cells. Here we show that pairing CF activation with bursts of PF activity triggers large (>10 microM) calcium signals in Purkinje cell dendrites. When PFs are densely activated, signals span whole dendritic branchlets and are mediated by voltage-dependent calcium entry. When PFs are sparsely activated, however, signals are restricted to single spines and blocked by metabotropic glutamate receptor antagonists. Single-spine signals and sparse-stimulation LTD are also blocked by thapsigargin, indicating that calcium must be released from stores. Single-spine signals and sparse-stimulation LTD are greatest when PF activation precedes the CF activation within 50-200 ms. This timing rule matches the properties of several forms of motor learning, providing a link between behavior and functional properties of cerebellar synaptic plasticity.
Wang
S S
SS
Biological Computation Research Department, Bell Laboratories, Lucent Technologies, 600 Mountain Avenue, Murray Hill, New Jersey 07974, USA.
Denk
W
W
Häusser
M
M
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001565:Benzoates; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019284:Thapsigargin / Q000494:pharmacology
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; C056723:FG 9041; D019284:Thapsigargin; C079693:4-carboxyphenylglycine; D005998:Glycine