1. We identify synthetic and naturally occurring molecules that are able to pass across the neural synapse, and we modify their structures using synthetic chemistry. Once applied to neurons at the beginning of a circuit, these molecules move throughout the brain, allowing us to take detailed pictures of neural circuitry.
Fluorescent molecules are designed to travel to the synapse once introduced to neurons of interest
The fluorescent probes interact with synapse cell surface receptors to facilitate labeling connected neurons
2. We create reactive probes that concentrate at the synapse where they undergo reaction to label connected neurons.
Reactive, neurotransmitter analogs are loaded into vesicles and released at the synapse
Neurotransmitter analogs convert pro-fluorescent molecules on connected cells into fluorophores
R = Bioorthogonal reactive group for reaction with corresponding groups at the synapse