Seminars

Our brain functions depend on connections between billions of neurons. These connections or synapses are believed to be disrupted in many neuropsychiatric disorders including autism, schizophrenia, and Alzheimer's disease. However, molecular mechanisms underlying synaptic function and dysfunction are largely unknown. Recently, we have developed a technique termed SLENDR to image endogenous proteins in the brain tissue using CRISPR-Cas9 mediated in vivo genome editing. By inserting a tag sequence into a gene of interest, SLENDR enables us to image a tagged endogenous protein with high specificity and contrast in small neuronal compartments such as synapses. In addition, we have recently developed fluorescence resonance energy transfer (FRET)-based biosensors for multiple small GTPases, and imaged their activities at single synapses by using two-photon fluorescence lifetime imaging (2pFLIM). I will discuss how these tools can help to understand molecular regulation of synapses in healthy and diseased brain.