Abstract
'Silent synapses' show responses from high-affinity NMDA receptors (NMDARs) but not low-affinity AMPA receptors (AMPARs), but gain AMPAR responses upon long-term potentiation (LTP). Using the rapidly reversible NMDAR antagonist l-AP5 to assess cleft glutamate concentration ([glu]cleft), we found that it peaked at <<170 microM at silent neonatal synapses, but greatly increased after potentiation. Cyclothiazide (CTZ), a potentiator of AMPAR, revealed slowly rising AMPA EPSCs at silent synapses; LTP shortened their rise times. Thus, LTP at silent synapses increased rate-of-rise and peak amplitude of [glu]cleft. Release probability reported by NMDARs remained unchanged during LTP, implying that [glu]cleft increases arose from immediately presynaptic terminals. Our data suggest that changes in the dynamics of fusion-pore opening contribute to LTP.
Publication types
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Research Support, Non-U.S. Gov't
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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Antihypertensive Agents / pharmacology
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Benzothiadiazines / pharmacology
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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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Extracellular Space / chemistry
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Extracellular Space / metabolism
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Glutamic Acid / pharmacokinetics*
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Patch-Clamp Techniques
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Pyramidal Cells / chemistry
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Pyramidal Cells / physiology
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Rats
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Receptors, N-Methyl-D-Aspartate / physiology
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Synapses / chemistry
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Synapses / drug effects
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Synapses / physiology*
Substances
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Antihypertensive Agents
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Benzothiadiazines
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Excitatory Amino Acid Antagonists
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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cyclothiazide