Abstract
Activity-dependent synaptic delivery of GluR1-, GluR2L-, and GluR4-containing AMPA receptors (-Rs) and removal of GluR2-containing AMPA-Rs mediate synaptic potentiation and depression, respectively. The obvious puzzle is how synapses maintain the capacity for bidirectional plasticity if different AMPA-Rs are utilized for potentiation and depression. Here, we show that synaptic AMPA-R exchange is essential for maintaining the capacity for bidirectional plasticity. The exchange process consists of activity-independent synaptic removal of GluR1-, GluR2L-, or GluR4-containing AMPA-Rs and refilling with GluR2-containing AMPA-Rs at hippocampal and cortical synapses in vitro and in intact brains. In GluR1 and GluR2 knockout mice, initiation or completion of synaptic AMPA-R exchange is compromised, respectively. The complementary AMPA-R removal and refilling events in the exchange process ultimately maintain synaptic strength unchanged, but their long rate time constants ( approximately 15-18 hr) render transmission temporarily depressed in the middle of the exchange. These results suggest that the previously hypothesized "slot" proteins, rather than AMPA-Rs, code and maintain transmission efficacy at central synapses.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anesthetics, Local / pharmacology
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Animals
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Animals, Newborn
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Brain / cytology*
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Electric Stimulation / methods
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Green Fluorescent Proteins / metabolism
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In Vitro Techniques
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Long-Term Potentiation / radiation effects
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Long-Term Synaptic Depression / radiation effects
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Magnesium / pharmacology
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Mice
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Mice, Knockout
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Neuronal Plasticity / radiation effects
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Neurons / drug effects
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Neurons / physiology*
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Neurons / radiation effects
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Neurons / virology
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Patch-Clamp Techniques / methods
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Rats
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Receptors, AMPA / classification
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Receptors, AMPA / deficiency
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Receptors, AMPA / genetics
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Receptors, AMPA / physiology*
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Synaptic Transmission / radiation effects
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Tetrodotoxin / pharmacology
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Time Factors
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Transfection / methods
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Vibrissae / innervation
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Vibrissae / physiology
Substances
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Anesthetics, Local
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Receptors, AMPA
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Green Fluorescent Proteins
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Tetrodotoxin
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Magnesium
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glutamate receptor ionotropic, AMPA 2
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glutamate receptor ionotropic, AMPA 1