AMPA receptor inhibition by synaptically released zinc
Author(s)Kalappa, Bopanna I.; Anderson, Charles T.; Tzounopoulos, Thanos; Goldberg, Jacob Michael; Lippard, Stephen J.
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Ionotropic glutamate AMPA receptors (AMPARs) play a fundamental role in normal function and plasticity of the brain, and they are also involved in many brain disorders. Despite the central role of AMPARs in neurobiology, the modulation of synaptic AMPA responses by endogenous modulators remains not well understood. Here, in three synapses found in two different brain areas, we provide the first evidence, to our knowledge, that endogenous zinc is coreleased with glutamate and modulates the strength of synaptic AMPAR responses. Because in many neocortical areas more than 50% of excitatory presynaptic terminals contain zinc within their glutamatergic vesicles, our findings establish zinc as a general neuromodulator that allows for fine-tuning and plasticity of glutamatergic fast synaptic transmission in the brain.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
Kalappa, Bopanna I.; Anderson, Charles T.; Goldberg, Jacob M.; Lippard, Stephen J. and Tzounopoulos, Thanos. “AMPA Receptor Inhibition by Synaptically Released Zinc.” Proceedings of the National Academy of Sciences 112, 51 (December 2015): 15749–15754 © 2015 National Academy of Sciences
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