High-resolution optical approaches to study dendritic signaling

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Understanding the mechanisms by which nerve cells transmit information and adapt their communication has progressed through the identification of the molecular components of synapses as well as the electrochemical nature of synaptic signals. However, for the majority of these components and signals, we know little about how they operate, propagate and interact during neurotransmission. To fully understand how synapses work, we must be able to resolve their molecular components and elementary signals within living neural circuits and to monitor them at length and time scales relevant to neurotransmission. Toward this aim, we have developed a Neurophotonics Research Program focussing on the development of advanced optical methods -in some cases beyond the resolution of light- to resolve the spatial and temporal dynamics of proteins and signals during synaptic transmission and to determine how these dynamics affect synaptic function. This Program is at the interface between Optics and Neurobiology. It bridges recent advances in optical methods, fluorescent probes, and cellular and molecular neuroscience. It trains a new generation of HQP in Biophotonics, supported by our Training Program in Biophotonics.***The general goal of our Program is to understand how temporally- and spatially-encoded dendritic electrical signals are decoded into specific information. We wish to understand how neuronal activities are decoded from the initial electrical signals at the membrane into i) transient intracellular signals and then into ii) longer-lasting biochemical signals iii) and synaptic plasticity***To study these problems, our Research Program has progressed in the last term, particularly on the design and improvements of optical methods to resolve and manipulate signaling events in dendrites of cultured neurons with improved spatial and temporal resolutions.***We specifically ask: How is electrical activity propagated from spines to dendrite? How does CaMKII decode the frequencies of calcium oscillations in dendrites? How does CaMKII propagate long-lasting memory? We address these questions by combining optical methods to monitor changes in membrane potentials, calcium imaging, FRET-FLIM to monitor protein interactions and activation, and optical nanoscopy to resolve protein interactions at the nanoscale. ***Our Research Program should help understanding the molecular processes that neurons use to encode their synaptic and electrical activities inside their dendrites. It will continue to advance optical methods to push the limits of resolution of live imaging in neurons. Our Research Program, at the interface between cellular neurobiology and optics, mainly trains physicists, engineers and chemists, who combine their skills to advance our knowledge of neuronal function and to improve our methods for advancing cellular and molecular neuroscience.*****