Copper is an endogenous modulator of neural circuit spontaneous activity

Sheel C. Dodani, Alana Firl, Jefferson Chan, Christine I. Nam, Allegra T. Aron, Carl S. Onak, Karla M. Ramos-Torres, Jaeho Paek, Corey M. Webster, Marla B. Feller, Christopher J. Chang

Research output: Contribution to journalArticlepeer-review


For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3(CF3), a new fluorescent Cu+ sensor for one- and twophoton imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

Original languageEnglish (US)
Pages (from-to)16280-16285
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 18 2014
Externally publishedYes


  • Copper signaling
  • Fluorescent sensor
  • Molecular imaging
  • Neural activity

ASJC Scopus subject areas

  • General


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