Postfusional regulation of cleft glutamate concentration during LTP at 'silent synapses'

Nat Neurosci. 2000 Apr;3(4):330-6. doi: 10.1038/73895.


'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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Benzothiadiazines / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Extracellular Space / chemistry
  • Extracellular Space / metabolism
  • Glutamic Acid / pharmacokinetics*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Patch-Clamp Techniques
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / physiology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / chemistry
  • Synapses / drug effects
  • Synapses / physiology*


  • Antihypertensive Agents
  • Benzothiadiazines
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • cyclothiazide