Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses

Neuron. 2008 Jan 10;57(1):121-34. doi: 10.1016/j.neuron.2007.11.023.


The physiological conditions under which adenosine A2A receptors modulate synaptic transmission are presently unclear. We show that A2A receptors are localized postsynaptically at synapses between mossy fibers and CA3 pyramidal cells and are essential for a form of long-term potentiation (LTP) of NMDA-EPSCs induced by short bursts of mossy fiber stimulation. This LTP spares AMPA-EPSCs and is likely induced and expressed postsynaptically. It depends on a postsynaptic Ca2+ rise, on G protein activation, and on Src kinase. In addition to A2A receptors, LTP of NMDA-EPSCs requires the activation of NMDA and mGluR5 receptors as potential sources of Ca2+ increase. LTP of NMDA-EPSCs displays a lower threshold for induction as compared with the conventional presynaptic mossy fiber LTP; however, the two forms of LTP can combine with stronger induction protocols. Thus, postsynaptic A2A receptors may potentially affect information processing in CA3 neuronal networks and memory performance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Long-Term Potentiation / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission / methods
  • Mossy Fibers, Hippocampal / physiology*
  • Mossy Fibers, Hippocampal / ultrastructure
  • N-Methylaspartate / pharmacology*
  • Phenethylamines / pharmacology
  • Pyrimidines / pharmacology
  • Receptor, Adenosine A2A / physiology*
  • Synapses / drug effects*
  • Synapses / physiology
  • Synapses / ultrastructure
  • Triazoles / pharmacology


  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Phenethylamines
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Triazoles
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • N-Methylaspartate
  • Adenosine
  • Calcium