With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Dan Fu and his group at the University of Washington - Seattle are devising new ways of studying neurotransmitters - the small molecules (such as dopamine and acetylcholine) that play key roles as chemical messengers between neurons in the brain. Specifically, the Fu group is developing ultrasensitive imaging tools to probe the storage, release, and recycling of neurotransmitters. Better understanding of these dynamics is essential to understanding neuronal function in the brain. Professor Fu's approach uses powerful imaging techniques that rely on the unique spectra of neurotransmitters to quantitatively map their distribution in model neurons. The project aligns well with the BRAIN initiative by providing missing chemical information on neurotransmission. The ultimate goal is to gain insight into the roles of various neurotransmitters in modulating brain activities in fundamental processes such as learning and memory. The Fu group is leveraging their expertise in spectroscopy and microscopy to develop demonstrations and teaching laboratory experiments targeting students across all ages, especially underrepresented minority students in local high schools and community colleges, with the goal of enhancing their physical science skills and interests for future careers in science and engineering. These activities are designed to demystify "blackbox" research spectrometers by using 3D printing and off-the-shelf consumer products to build cheap spectrometers for classroom use. The impact of these new instruments and labs will be amplified by online dissemination to resource-limited colleges and high schools through a dedicated website and YouTube instructional videos.
Existing tools for studying small molecule neurotransmitters (e.g. amperometry and cyclic voltammetry) are often limited to detection of extracellular molecules and lack the capability of quantifying spatially resolved vesicular neurotransmitter content. Stimulated Raman scattering (SRS) microscopy is an emerging pulsed-laser chemical imaging technique that efficiently excites intrinsic molecular vibrations. To enable use of SRS for noninvasive monitoring of the distribution and dynamics of various neurotransmitters, the Fu group is developing new SRS imaging techniques based on a combination of ultrafast laser engineering, pulse shaping, Fourier-transform detection, and new microscopy instrumentation to improve the sensitivity of SRS microscopy by 50-fold. This improvement will enable measurement of neurotransmitter content of single vesicles and multiplex detection of different neurotransmitters in neuronal cells. Following validation by electrochemical measurements, the approach will provide the first nonperturbative measurements of neurotransmitter distribution, release percentage, and recycling time in model neuronal cells. The educational plan of this CAREER proposal focuses on developing low-cost, modular instruments and designing science labs to fill unmet needs in (1) educating undergraduate students on fundamentals of instrument science and technology, and (2) enhancing academic preparation of underrepresented minority (URM) high school students for STEM education.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
