کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4321061 1291566 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Zinc Dynamics and Action at Excitatory Synapses
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Zinc Dynamics and Action at Excitatory Synapses
چکیده انگلیسی


• Ambient zinc levels are low (<10 nM), insufficient to occupy GluN2A-NMDA receptors
• Repetitive synaptic stimuli are required for zinc modulation of NMDA-EPSCs
• By targeting GluN2A-NMDARs, zinc controls synaptic integration and plasticity
• Zinc action is prominent at both hippocampal mossy fibers and SC-CA1 synapses

SummaryDecades 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 82, Issue 5, 4 June 2014, Pages 1101–1114
نویسندگان
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