Abstract
We have used rats and mice with mutations in myosin-Va to evaluate the range 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 Purkinje cells. Long-term synaptic depression (LTD) is absent at the parallel fiber synapses of the mutants, even though the structure and function of these synapses otherwise appear normal. This loss of LTD is associated with selective 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 release Ca2+ locally in the dendritic spines to produce LTD and indicate that one function of dendritic spines is to target IP3-mediated Ca2+ release to the proper subcellular domain.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Benzoates / pharmacology
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Calcium Channels / deficiency
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Calcium Channels / metabolism
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Calcium Signaling / physiology*
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Cerebellum / cytology
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Cerebellum / metabolism
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Glycine / analogs & derivatives
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Glycine / pharmacology
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In Vitro Techniques
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Inositol 1,4,5-Trisphosphate Receptors
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Intermediate Filament Proteins / deficiency
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Intermediate Filament Proteins / genetics
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Mice
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Mice, Neurologic Mutants
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Myosin Heavy Chains*
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Myosin Type V*
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Patch-Clamp Techniques
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Purkinje Cells / metabolism
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Purkinje Cells / ultrastructure
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Rats
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Rats, Mutant Strains
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Receptors, Cytoplasmic and Nuclear / deficiency
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Receptors, Cytoplasmic and Nuclear / metabolism
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Synaptic Transmission / genetics
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Time
Substances
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Benzoates
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Calcium Channels
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Excitatory Amino Acid Antagonists
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ITPR1 protein, human
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Inositol 1,4,5-Trisphosphate Receptors
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Intermediate Filament Proteins
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Myo5a protein, mouse
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Myo5a protein, rat
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Receptors, Cytoplasmic and Nuclear
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6-Cyano-7-nitroquinoxaline-2,3-dione
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4-carboxyphenylglycine
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2-Amino-5-phosphonovalerate
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Myosin Type V
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Myosin Heavy Chains
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Glycine