title: Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Oxford, U.K.
authors.forename: N
authors.initials: N
authors.lastname: Berretta
authors.forename: R S
authors.initials: RS
authors.lastname: Jones
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium