Tools to decipher neuronal signaling and compoutation

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The objective of my NSERC program is to understand the biophysical determinants of neural signalling and computation. That is, to identify the substrates of cell to cell signalling and of signal integration that underlie information processing in neural circuits. In this context, my research has focused on 1) how the structural and functional organizations of synapses affects information transfer between cells and 2) how synaptic mechanisms interact with the intrinsic properties of nerve cells to shape information coding. To achieve this, I continuously seek to develop novel, enabling approaches and analytical tools. We develop: 1) signal analysis tools to resolve biophysical events at the limits of what our experimental tools allow us to address, 2) novel, high-resolution microscopy and nanotechnology tools to resolve structural determinants underlying synaptic arrangements, and 3) computer-based modeling to identify how synaptic mechanisms determine information coding by individual neurons and small neural circuits.***1) Properties of receptor/channels at functional synapses***Modification of the strength of synaptic transmission involve several mechanisms (receptor numbers, properties, positioning, etc.); to understand the basics of synaptic plasticity, we develop approaches to resolve channel numbers at live synapses: Two approaches will be pursued:***1a) A modification of our noise analysis algorithm***1b) An adaptation of our SpIDA image analysis approach to structurally resolve receptor numbers at synapses.***2) High-resolution live cell imaging and micromanipulation***Activity-dependent spine reshaping are an important determinants of synaptic funciton. To follow the structural dynamics of submicron-scale cellular compartments, we develop high-resolution approaches:***2a) We exploit Atomic Force Microscopy as ultimate micropositionners and micromanipulators i) to study forces underlying ligand-receptor interaction and ii) to artificially engineer network topologies in neuronal cultures.***2b) We developed high-resolution SLAM Microscopy and will continue to explore resolution enhancement using other beam shaping and polarization approaches.***3- Cl- dynamics and information processing***We study the multiple impacts of altered Cl- dynamics on neural computation using different, complementary computational approaches:***3a) We will explore how Cl- dynamics affect information transfer combining electrodiffusion modeling and a low dimensional generic model.***3b) Cost of inhibition: we will investigate the advantage of maintaining hyperpolarizing inhibition given its energy cost.******   The research is relevant to the training of personnel with background in mathematics, computer sciences and physics (photonics and nanotechnology) who have an interest in applying their expertise in computational approaches to the understanding of neurobiological mechanisms.**