Life Sciences Faculties

The analog computation at the chemical synapse that underlies cognition depends on a highly compartmentalized, tightly regulated, and complex network of interactions between synaptic activity and hundreds of proteins and the mechanisms that regulate them. For a top-down study of how the network operates in concert, I present a modular, versatile approach for combined imaging of multiprotein composition, activation states, ion and neurotransmitter fluxes, and mRNA translation across the same individual synapses. I will show how this approach extends to other subcellular systems such as mitochondria. I will discuss the use of Bayesian network inference to extract biological insight from high-dimensional, multimodal synapse distributions. Finally, I will present applications of this approach to identify convergent molecular phenotypes across autism and schizophrenia-associated genes, and for an in-depth study of the complex synaptic response to genetic and chemical perturbations of GluN2A.