Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex

Neuroscience. 1996 Nov;75(2):339-44. doi: 10.1016/0306-4522(96)00301-6.


N-Methyl-D-aspartate receptors are fundamental for neuronal plasticity and development in the CNS. Most studies have examined postsynaptic roles of this receptor, but there are also indications for a presynaptic location and function. Here, we provide electrophysiological evidence for the existence of presynaptic N-methyl-D-aspartate receptors which can tonically facilitate glutamate release in the CNS. The N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoate reduced the frequency, but not amplitude, of glutamate-mediated spontaneous excitatory postsynaptic currents in layer II neurons of the rat entorhinal cortex. This effect was also observed in the presence of tetrodotoxin and when postsynaptic N-methyl-D-aspartate receptors were blocked by dialysis with dizocilpine maleate. When extracellular calcium was replaced with strontium, 2-amino-5-phosphonopentanoate reduced the "tail" of spontaneous excitatory postsynaptic currents that followed an evoked excitatory postsynaptic current. Finally, there was a tendency for paired-pulse facilitation of excitatory postsynaptic currents evoked at short (50 ms) intervals with postsynaptic N-methyl-D-aspartate receptors blocked) to be reduced by 2-amino-5-phosphonopentanoate, although this did not reach significance. These data strongly support the presence of presynaptic N-methyl-D-aspartate autoreceptors which may facilitate glutamate release in layer II of the entorhinal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Calcium / metabolism
  • Dizocilpine Maleate / pharmacology
  • Electrophysiology
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / metabolism*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, Presynaptic / drug effects
  • Receptors, Presynaptic / metabolism*


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Presynaptic
  • Glutamic Acid
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate
  • Calcium