Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16280-5. doi: 10.1073/pnas.1409796111. Epub 2014 Nov 5.

Copper is an endogenous modulator of neural circuit spontaneous activity.

Author information

1
Departments of Chemistry and.
2
Vision Sciences Graduate Program, Department of Optometry.
3
Departments of Chemistry and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
4
Molecular and Cell Biology.
5
Molecular and Cell Biology, Helen Wills Neuroscience Institute, and.
6
Departments of Chemistry and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720 Molecular and Cell Biology, Helen Wills Neuroscience Institute, and chrischang@berkeley.edu.

Abstract

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 two-photon 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.

KEYWORDS:

copper signaling; fluorescent sensor; molecular imaging; neural activity

PMID:
25378701
PMCID:
PMC4246333
DOI:
10.1073/pnas.1409796111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center