Elsevier

Brain Research

Volume 576, Issue 2, 3 April 1992, Pages 197-202
Brain Research

Glycine is required for NMDA receptor activation: electrophysiological evidence from intact rat hippocampus

https://doi.org/10.1016/0006-8993(92)90680-8Get rights and content

Abstract

Fimbrial/commissural stimulation evokes a prolonged negative field potential in stratum radiatum of CA1 region of the rat hippocampus, in situ, upon activation of N-methyl-d-aspartate (NMDA)_receptors. This activity can be induced by iontophoresis of NMDALA (50 nA) or glycine (50–100 nA) during low-frequency stimulation. 7-Cl-Kynurenate (10–30 nA) fully antagonized the NMDA receptor-mediated negative wave induced not only by glycine (N = 3) but also by NMDLA (N = 9), suggesting that activation of NMDA receptors is not possible without glycine binding. 7-Cl-Kynurenate also depressed the extracellular negative d.c. potential shifts appearing during iontophoresis of NMDLA. Stimulation with brief, high-frequency trains evoked a negative wave of 2.1 ± 0.2mV and 176 ± 4ms(N = 20) on the hippocampal field response following the last stimulus. Ketamine (100–200nA, N = 6) and MK-801 (50–200nA, N = 7) blocked the negative wave by 74 ± 13 and 62 ± 8%, respectively, while glycine (100 nA) potentiated it by 35 ± 2% (N = 6), indicating that it had a component mediated by NMDA receptors. 7-Cl-Kynurenate (100 nA) antagonized this activity at a comparable rate to the NMDA receptor antagonists (67 ± 8%, N = 4). A similar negative wave of 0.9 ± 0.2mV and 41 ± 3ms(N = 12) was evoked in hippocampal slices by high-frequency orthodromic stimulation. Potentiation of this activity upon lowering Mg2+ in ACSF from 1.3 to 0.5 mM further supported that it had an NMDA-mediated component. The negative wave was depressed by iontophoresis of MK-801 (34 ± 1%, N = 2) and 7-Cl-kynurenate (39 ± 12%, N = 5). Perfusion with 7-Cl-kynurenate (10–30 μM, N = 4), MK-801 (100 μM, N = 3) and 2.6 mM Mg2+ (N= 3) also inhibited this wave by 47 ± 14, 32 ± 15 and 54 ± 5%, respectively. Antagonism by 7-Cl-kynurenate of the part of the hippocampal field potential sensitive to NMDA receptor antagonists suggests that binding of endogenous glycine to the NMDA receptor is required for NMDA receptor activation.

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