Details

Autor(en) / Beteiligte

• Kalappa, Bopanna I.
• Anderson, Charles T.
• Goldberg, Jacob M.
• Lippard, Stephen J.
• Tzounopoulos, Thanos

Titel

AMPA receptor inhibition by synaptically released zinc

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-12, Vol.112 (51), p.15749-15754

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.