With this award, Scott T. Laughlin from Stony Brook University, funded by the Chemistry of Life Processes Program in the Chemistry Division of the National Science Foundation, will investigate the use of synthetic molecules for mapping the connections between neurons in the brain. The human brain's ~90 billion neurons allow us to think, move, and respond to stimuli. The brain's amazing properties stem from neural circuits, which perform logical operations based on the timing of neural activity and the specific connections between neurons in a circuit. Strategies for visualizing and controlling neural activity abound, but there are very few methods that enable direct imaging of neural circuit connectivity, and those that exist are imperfect. Bridging the fields of chemistry and neuroscience enables a novel strategy that will facilitate the direct visualization of neural circuit connectivity in order to better understand the brain. Importantly, this work will expose graduate and undergraduate students to cutting-edge methods and ideas in chemistry and neuroscience.
The goal of this research is to create small molecules that illuminate the neurons that are connected to each other in a neural circuit. Currently, there are no known small molecules that display this property. However, there are a variety of naturally-occurring entities that mark neural circuits by moving through neural synapses, which are the functional connections between neurons. For example, some proteins called lectins can cross the synapse by virtue of their affinity for synapse cell surface sugars, but they are large, toxic, not easily altered, and slow to label consecutive neurons in a circuit. Interestingly, diverse lectins, from different organisms and with different sugar affinities share the ability to cross the synapse, suggesting that the most important property that endows lectins with the ability to cross the synapse is their general sugar affinity, and not a particular protein feature or specific sugar affinity. This research explores the idea that small molecules that mirror the trans-synaptic lectin's affinity for sugars will be able to cross the synapse and serve as tracers for mapping the brain's neural circuitry. The use of these trans-synaptic small molecules has the potential to enable an improved and detailed understanding of the brain.