Presynaptic NR2B-containing NMDA autoreceptors mediate gluta-matergic synaptic transmission in the rat visual cortex.
N-methyl-D-aspartate (NMDA) receptors (NMDA-Rs) have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study investigated the subunit composition of the presynaptic NMDA-Rs in layer II/III pyramidal neurons of the rat visual cortex. We recorded evoked a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (eEPSCs) using whole-cell voltage clamp with the open-channel NMDA receptor (NMDA-R) blocker, (+)-5-Methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801), in the recording pipette. We found that the paired-pulse ratio (PPR) by two successive stimuli with inter-pulse intervals of 50 ms was significantly increased by D-APV, a selective NMDA-R antagonist. Using a specific antagonist for NR2B-NMDA-Rs, (alphaR,betaS)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol hydrochloride (Ro 25-6981), instead of d-2-amino-5-phosphonovalerate (D-APV), we found that the PPR of eEPSCs was also significantly increased. Moreover, Zn(2+), an NR2A-NMDA-R antagonist, did not influence on the PPR. These results suggest that presynaptic NR2B-containing NMDA-Rs are located in layer II/III pyramidal neurons of the rat visual cortex, and that presynaptic NR2B-containing NMDA autoreceptors but not NR2A-containing NMDA autoreceptors mediate glutamate release in the rat visual cortex. Moreover, these findings may be clinically relevant to schizophrenia, where enhancing NMDA-R function is considered to be a promising strategy for treatment of the disease.
Li
Yan-Hai
YH
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China. liyanhai@mail.xjtu.edu.cn
Wang
Jue
J
Zhang
Guangjun
G
D000818:Animals; D000831:Animals, Newborn; D017660:Autoreceptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology* / Q000502:physiology*
D017660:Autoreceptors; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid