 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 8, 3733-3741, Copyright © 1988 by Society for Neuroscience
Modulation of excitatory synaptic transmission by glycine and zinc in cultures of mouse hippocampal neurons
ID Forsythe, GL Westbrook and ML Mayer
Laboratory of Developmental Neurobiology, NICHD, Bethesda, Maryland 20892.
The monosynaptic EPSP between cultured hippocampal neurons is mediated by
activation of 2 classes of excitatory amino acid receptors. Kainate or
quisqualate receptors generate a fast conventional EPSP, while NMDA
receptors mediate a slow, voltage-sensitive EPSP. Recently, 2 substances
have been shown to modulate the activity of the NMDA receptor-channel
complex: glycine increases the probability of channel opening, while zinc
acts as a noncompetitive antagonist. Since these substances are present in
the CNS and thus may function as neuromodulators, we have examined their
role in excitatory synaptic transmission in hippocampal cultures using the
whole-cell-patch- recording technique. The slow, NMDA-receptor-mediated
EPSP was strikingly dependent on the presence of a conditioning substance
that gradually accumulated in the extracellular fluid during a 30 min
incubation in physiological saline. Washout of the conditioned medium
eliminated the slow EPSP, and perfusion with physiological saline
containing 1 microM glycine restored the slow EPSP to control levels.
Furthermore, conditioned medium collected from astroglial-only cultures
also potentiated the response to NMDA. Zinc (20-50 microM) overcame the
potentiation of the response by glycine and resulted in a reversible block
of the slow EPSP, providing the first evidence for a direct action of zinc
on excitatory synaptic transmission. Our results show that the expression
of the slow EPSP may be subject to regulation by several endogenous
substances: positive modulation by glycine (or a glycine-like substance),
which can be released from astroglial cells, and negative modulation by
physiological levels of zinc.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
|
|
 
N. Lavoie, M. R. Peralta III, M. Chiasson, K. Lafortune, L. Pellegrini, L. Seress, and K. Toth
Extracellular chelation of zinc does not affect hippocampal excitability and seizure-induced cell death in rats
J. Physiol.,
January 1, 2007;
578(1):
275 - 289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Cote, M. Chiasson, M. R Peralta III, K. Lafortune, L. Pellegrini, and K. Toth
Cell type-specific action of seizure-induced intracellular zinc accumulation in the rat hippocampus
J. Physiol.,
August 1, 2005;
566(3):
821 - 837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Harris, W. J. Brecht, Q. Xu, R. W. Mahley, and Y. Huang
Increased tau Phosphorylation in Apolipoprotein E4 Transgenic Mice Is Associated with Activation of Extracellular Signal-regulated Kinase: MODULATION BY ZINC
J. Biol. Chem.,
October 22, 2004;
279(43):
44795 - 44801.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. G. Smart, A. M. Hosie, and P. S. Miller
Zn2+ Ions: Modulators of Excitatory and Inhibitory Synaptic Activity
Neuroscientist,
October 1, 2004;
10(5):
432 - 442.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y. Yang, W. Ge, Y. Chen, Z. Zhang, W. Shen, C. Wu, M. Poo, and S. Duan
Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine
PNAS,
December 9, 2003;
100(25):
15194 - 15199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Atkinson, S. C. Bell, M. De Vivo, L. R. Kowalski, S. M. Lechner, V. I. Ognyanov, C.-S. Tham, C. Tsai, J. Jia, D. Ashton, et al.
ALX 5407: A Potent, Selective Inhibitor of the hGlyT1 Glycine Transporter
Mol. Pharmacol.,
December 1, 2001;
60(6):
1414 - 1420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Horning and P. Q. Trombley
Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms
J Neurophysiol,
October 1, 2001;
86(4):
1652 - 1660.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-J. Eom, E. Y. Kim, J. E. Lee, H. J. Kang, J. Shim, S. U. Kim, B. J. Gwag, and E.-J. Choi
Zn2+ Induces Stimulation of the c-Jun N-Terminal Kinase Signaling Pathway through Phosphoinositide 3-Kinase
Mol. Pharmacol.,
April 16, 2001;
59(5):
981 - 986.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
W. Danysz and C. G. Parsons
Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications
Pharmacol. Rev.,
December 1, 1998;
50(4):
597 - 664.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Trepel, K. R. Duffy, V. D. Pegado, and K. M. Murphy
Patchy Distribution of NMDAR1 Subunit Immunoreactivity in Developing Visual Cortex
J. Neurosci.,
May 1, 1998;
18(9):
3404 - 3415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Paoletti, P. Ascher, and J. Neyton
High-Affinity Zinc Inhibition of NMDA NR1-NR2A Receptors
J. Neurosci.,
August 1, 1997;
17(15):
5711 - 5725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Erickson, G. Hollopeter, S. A. Thomas, G. J. Froelick, and R. D. Palmiter
Disruption of the Metallothionein-III Gene in Mice: Analysis of Brain Zinc, Behavior, and Neuron Vulnerability to Metals, Aging, and Seizures
J. Neurosci.,
February 15, 1997;
17(4):
1271 - 1281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-S. Rioult-Pedotti
Intrinsic NMDA-Induced Oscillations in Motoneurons of an Adult Vertebrate Spinal Cord Are Masked by Inhibition
J Neurophysiol,
February 1, 1997;
77(2):
717 - 730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
.gif?ad=17923&adview=true)
