Tools to decipher neuronal signaling and compoutation

破译神经元信号和计算的工具

• 批准号: RGPIN-2015-04499
• 负责人: DeKoninck, Yves
• 金额: $ 7.43万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613003
• 关键词: Tools; decipher; neuronal; signaling; compoutation

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.

我的NSERC项目的目标是了解神经信号和计算的生物物理决定因素。也就是说，识别细胞间信号传递和神经回路中信息处理的信号整合的底物。在此背景下，我的研究主要集中在1)突触的结构和功能组织如何影响细胞间的信息传递；2)突触机制如何与神经细胞的内在特性相互作用以形成信息编码。为了实现这一目标，我不断寻求开发新颖的、可行的方法和分析工具。我们开发了：1)信号分析工具，以解决我们的实验工具允许我们解决的生物物理事件；2)新颖的高分辨率显微镜和纳米技术工具，以解决突触排列背后的结构决定因素；3)基于计算机的建模，以确定突触机制如何决定单个神经元和小神经回路的信息编码。