TY - JOUR
T1 - Modulation of excitatory synaptic transmission by glycine and zinc in cultures of mouse hippocampal neurons
AU - Forsythe, I. D.
AU - Westbrook, G. L.
AU - Mayer, M. L.
PY - 1988
Y1 - 1988
N2 - 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: glycind 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 μM glycine restored the slow EPSP to control levels. Furthermore, conditioned medium collected from atroglial-only cultures also potentiated the response to NMDA. Zinc (20-50 μM) 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. The characteristics of the glycine modulatory mechanism make it suited for a role as a tonic modulator, while zinc may have an acute mechanism of action.
AB - 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: glycind 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 μM glycine restored the slow EPSP to control levels. Furthermore, conditioned medium collected from atroglial-only cultures also potentiated the response to NMDA. Zinc (20-50 μM) 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. The characteristics of the glycine modulatory mechanism make it suited for a role as a tonic modulator, while zinc may have an acute mechanism of action.
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U2 - 10.1523/jneurosci.08-10-03733.1988
DO - 10.1523/jneurosci.08-10-03733.1988
M3 - Article
C2 - 2848107
AN - SCOPUS:0023811738
SN - 0270-6474
VL - 8
SP - 3733
EP - 3741
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -