While individual neurons are themselves sophisticated processors, the true computing power of the brain emerges from the massive connections each neuron makes with thousands of other neurons (i.e., connectome). Yet, how the brain connectome gives rise to its sophisticated functions and how it is altered by neuropsychiatric diseases remain largely unknown. The Lu Lab, working at the interface of chemistry and neuroscience, focuses on developing essential biochemical tools, advanced microscopy techniques, and computation to understand brain connectivity.

Multiscale Brain Circuit Imaging

With their unique morphologies, neurons in the brain operate across multiple scales, projecting micrometer-diameter axons over millimeters or even centimeters to form nanoscale connections via synapses. Each neuron orchestrates thousands of synaptic connections, creating an extremely complex network that underlies our behaviors and thoughts. Capturing the structural features of the brain across multiple scales remains challenging. We develop novel electron microscopy and X-ray microscopy along with tissue processing methods to reveal brain circuits with greater scope and detail.

Multiplexed Molecular Labeling

Neurons exhibit extraordinary molecular diversity, which underpins their distinct ways of processing and transmitting signals. Integrating this molecular information with connectomic imaging is crucial for understanding how brain circuits function. Simultaneously labeling disease-related biomarkers further helps identify underlying abnormalities. We develop miniaturized protein binders and use them to build a multiplexed molecular imaging platform compatible with ultrastructural imaging. This approach correlates molecular and structural details for a comprehensive understanding of brain circuits in health and diseases.