Zinc dynamics and action at excitatory synapses.
Neuron. 2014-06-01; 82(5): 1101-1114
DOI: 10.1016/j.neuron.2014.04.034
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1. Neuron. 2014 Jun 4;82(5):1101-14. doi: 10.1016/j.neuron.2014.04.034.
Zinc dynamics and action at excitatory synapses.
Vergnano AM(1), Rebola N(2), Savtchenko LP(3), Pinheiro PS(2), Casado M(1),
Kieffer BL(4), Rusakov DA(3), Mulle C(5), Paoletti P(6).
Author information:
(1)Ecole Normale Supérieure, Institut de Biologie de l’ENS (IBENS), F-75005
Paris, France; Inserm, U1024, F-75005 Paris, France; CNRS, UMR 8197, F-75005
Paris, France.
(2)Université de Bordeaux, Institut Interdisciplinaire de Neurosciences, F-33000
Bordeaux, France; CNRS UMR 5297, F-33000 Bordeaux, France.
(3)UCL Institute of Neurology, University College London, London, WC1N 3BG, UK.
(4)Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de
Strasbourg, CNRS, INSERM, 67404 Illkirch, France.
(5)Université de Bordeaux, Institut Interdisciplinaire de Neurosciences, F-33000
Bordeaux, France; CNRS UMR 5297, F-33000 Bordeaux, France. Electronic address:
.
(6)Ecole Normale Supérieure, Institut de Biologie de l’ENS (IBENS), F-75005
Paris, France; Inserm, U1024, F-75005 Paris, France; CNRS, UMR 8197, F-75005
Paris, France. Electronic address: .
Decades after the discovery that ionic zinc is present at high levels in
glutamatergic synaptic vesicles, where, when, and how much zinc is released
during synaptic activity remains highly controversial. Here we provide a
quantitative assessment of zinc dynamics in the synaptic cleft and clarify its
role in the regulation of excitatory neurotransmission by combining synaptic
recordings from mice deficient for zinc signaling with Monte Carlo simulations.
Ambient extracellular zinc levels are too low for tonic occupation of the
GluN2A-specific nanomolar zinc sites on NMDA receptors (NMDARs). However,
following short trains of physiologically relevant synaptic stimuli, zinc
transiently rises in the cleft and selectively inhibits postsynaptic
GluN2A-NMDARs, causing changes in synaptic integration and plasticity. Our work
establishes the rules of zinc action and reveals that zinc modulation extends
beyond hippocampal mossy fibers to excitatory SC-CA1 synapses. By specifically
moderating GluN2A-NMDAR signaling, zinc acts as a widespread activity-dependent
regulator of neuronal circuits.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2014.04.034
PMID: 24908489 [Indexed for MEDLINE]