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Updated: Aug 21, 2026
Longitudinal Two-Photon Imaging of Dorsal Hippocampal CA1 in Live Mice
Published on: June 19, 2019
ZP8, a neuronal zinc sensor with improved dynamic range; imaging zinc in hippocampal slices with two-photon
Christopher J Chang1, Elizabeth M Nolan, Jacek Jaworski
1Department of Chemistry, Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Abstract:
The synthesis of a difluorofluorescein monocarboxaldehyde platform and its use for preparing ZP8, a new member of the Zinpyr family of neuronal Zn(2+) sensors, are described. By combining an aniline photoinduced electron transfer (PET) switch and an electron-withdrawing fluorescein scaffold, ZP8 displays reduced background fluorescence and improved dynamic range compared to previous ZP probes. The bright sensor undergoes an 11-fold increase in fluorescence intensity upon Zn(2+) complexation (Phi = 0.03-0.35) with high selectivity over cellular concentrations of Ca(2+) and Mg(2+). In addition, sensors in the ZP family have been utilized for optical imaging in biological samples using two-photon microscopy (TPM). The cell-permeable ZP3 probe is capable of identifying natural pools of labile Zn(2+) within the mossy fiber synapses of live hippocampal slices using TPM, establishing the application of this technique for monitoring endogenous Zn(2+) stores.
