Abstract
Competitive synaptic remodeling is an important feature of developmental plasticity, but the molecular mechanisms remain largely unknown. Calcium/calmodulin-dependent protein kinase II (CaMKII) can induce postsynaptic changes in synaptic strength. We show that postsynaptic CaMKII also generates structural synaptic rearrangements between cultured cortical neurons. Postsynaptic expression of activated CaMKII (T286D) increased the strength of transmission between pairs of pyramidal neuron by a factor of 4, through a modest increase in quantal amplitude and a larger increase in the number of synaptic contacts. Concurrently, T286D reduced overall excitatory synaptic density and increased the proportion of unconnected pairs. This suggests that connectivity from some synaptic partners was increased while other partners were eliminated. The enhancement of connectivity required activity and NMDA receptor activation, while the elimination did not. These data suggest that postsynaptic activation of CaMKII induces a structural remodeling of presynaptic inputs that favors the retention of active presynaptic partners.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / genetics
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Anesthetics, Local / pharmacology
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Animals
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Animals, Newborn
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Aspartic Acid / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Count
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Cell Surface Extensions / physiology
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Cerebral Cortex / cytology
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Cerebral Cortex / physiology
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Dizocilpine Maleate / pharmacology
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Drug Interactions
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / genetics
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Excitatory Postsynaptic Potentials / physiology
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Fluorescent Dyes
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Gene Expression Regulation, Enzymologic*
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Green Fluorescent Proteins
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Immunohistochemistry
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Luminescent Proteins / metabolism
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Lysine / analogs & derivatives*
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Lysine / metabolism
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Mutation / physiology
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Nerve Tissue Proteins / metabolism
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Neuronal Plasticity / physiology
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Neurons / drug effects
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Neurons / physiology*
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Organ Culture Techniques
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Pyridinium Compounds / metabolism
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Quaternary Ammonium Compounds / metabolism
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Rats
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Rats, Long-Evans
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Synapses / enzymology*
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Synapses / genetics
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Synapsins / metabolism
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Synaptic Transmission / physiology
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Tetrodotoxin / pharmacology
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Threonine / genetics
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Transfection
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Valine / analogs & derivatives*
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Valine / pharmacology
Substances
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Anesthetics, Local
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Excitatory Amino Acid Antagonists
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FM1 43
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Fluorescent Dyes
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Luminescent Proteins
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Nerve Tissue Proteins
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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Synapsins
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postsynaptic density proteins
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Green Fluorescent Proteins
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Threonine
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Aspartic Acid
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Tetrodotoxin
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Dizocilpine Maleate
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2-amino-5-phosphopentanoic acid
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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biocytin
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Valine
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Lysine
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Alanine