Concluding Remarks And Future Directions

Significant advances have been made to provide the requisite methodology for understanding how zinc functions in the brain and CNS. Central to this goal is the development of new tools that can be utilized for studying Zn2+ in biological environments. We have highlighted recent progress in the design, synthesis, and characterization of fluorescent Zn2+ sensors and their application for real-time optical imaging in living systems. Because much of this work is still in its early stages, there are tremendous opportunities for scientists interested in problems at the bioinorganic chemistry/neuroscience interface. New tactics are required for expanding the repertoire of available imaging agents for Zn2+ and related analytes. Directions for future Zn2+ sensor design include improved ratiometric sensors for quantitation of endogenous Zn2+ pools, probes that span a wider range of Kd values, reagents that shift excitation/emission profiles towards the infrared region, and responsive fluorophores that can be targeted to specific intracellular and extracellular locations.

Of particular interest for the characterization of vesicular Zn2+ and its synaptic translocation are lipophilic probes with moderate binding affinities and fast response times. In addition, new instrumental advances for Zn2+ detection in vivo are emerging to complement these improved reagents, including optical microscopes with multiphoton excitation and the fabrication of fiber-optic probes. Taken together, these results demonstrate the value of fluorescent probes for Zn2+ and show their potential for imaging this ion in real time and space in living systems. As the tool kit for Zn2+ metalloneurochemistry continues to grow, so will our insight into how Zn2+ contributes to the function of our minds (see also the Addendum in [236]).

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