| Autor: |
Dodani SC; Departments of Chemistry and., Firl A; Vision Sciences Graduate Program, Department of Optometry., Chan J; Departments of Chemistry and., Nam CI; Departments of Chemistry and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720., Aron AT; Departments of Chemistry and., Onak CS; Departments of Chemistry and., Ramos-Torres KM; Departments of Chemistry and., Paek J; Departments of Chemistry and., Webster CM; Molecular and Cell Biology., Feller MB; Molecular and Cell Biology, Helen Wills Neuroscience Institute, and., Chang CJ; 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. |
| Abstrakt: |
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. |
