A major focus of modern neuroscience is understanding the role of neuromodulators in neural circuit function and development, in behavior, and their dysfunction in neurological disease. Neural circuit research has been revolutionized by powerful new optical techniques. Here we propose to use new near-infrared optical nanosensor technology to image dopamine. As a proof of principle, we will use this sensor to monitor dopamine release under physiological conditions in both the developing and adult retinas. The ability to combine neuromodulator imaging with other physiological measures in a well-defined neural circuit will greatly advance our understanding of neuromodulation, allowing us to elucidate its many impacts on normal and pathological circuits.
We will develop a new optical nanosensor to time-resolve dopamine release in a functional neural circuit. Large field imaging will enable to determine the spatiotemporal gradients of dopamine under physiological conditions. New near-infrared two-photon microscopy will enable us to integrate optical sensing of neuromodulators with two- photon calcium imaging of neural activity. This work will greatly expand the optical toolbox available for studying neural circuits.
