High resolution optical approaches to study dendritic signaling

研究树突信号传导的高分辨率光学方法

• 批准号: 250127-2012
• 负责人: DeKoninck, Paul
• 金额: $ 3.86万
• 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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570826
• 关键词: resolution; optical; approaches; study; dendritic

To understand how the brain works, we must learn how its components, the brain cells and particularly the neurons, transmit information and communicate. The main sites of neurotransmission are the billions of tiny synapses. Great progress toward understanding synaptic transmission has been made 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, much remains unknown about how they operate and interact during neurotransmission. To fully understand how synapses work, we need to resolve their molecular components and elementary signals within living neural circuits and to monitor them at length and time scales relevant to neurotransmission. Because synapses are so tiny (<1/1000 of a millimeter), we must push the limits of spatial resolution of our microscopes. Because neuronal communication is so rapid (milliseconds), we must also push our imaging to fast speed. Thus our efforts are focussed on the optimization of microscopy methods to understand how molecules inside neurons respond to and translate the electrical activity of neurons. Our approaches involve the preparation of cultures of neurons from the rat hippocampus. We introduce in these neurons genes which we modify to encode synaptic proteins containing a fluorescent tag. We then use advanced optical microscopes, most of which assembled in the laboratory, using special lasers and optical lenses, to track the fluorescent signals inside the neurons and their synapses as they communicate. We also use other types of fluorescent probes, such as nanocrystals and organic probes. Our main question is how do neurons encode their electrical activity into biochemical activity intracellularly. Through this Neurophotonics Research Program we hope to contribute to improve our understanding of the fundamental mechanisms that neurons use to communicate and to adapt their modes of communication to support learning and memory. Our Program is at the interface between Optics and Neurobiology. It trains a new generation of Highly Qualified Personel in Biophotonics, supported by an NSERC Training Program in Biophotonics.

要了解大脑是如何工作的，我们必须了解它的组成部分，脑细胞，特别是神经元，是如何传递信息和交流的。神经传递的主要部位是数十亿个微小的突触。通过对突触分子成分的识别以及突触信号的电化学性质，在理解突触传递方面取得了很大进展。然而，对于这些成分和信号的大部分，在神经传递过程中它们是如何运作和相互作用的，仍然未知。为了充分了解突触是如何工作的，我们需要在活的神经回路中解析它们的分子组成和基本信号，并在与神经传递相关的长度和时间尺度上监测它们。因为突触非常微小（小于1/1000毫米），我们必须突破显微镜空间分辨率的极限。因为神经元之间的交流是如此之快（毫秒级），我们也必须加快成像速度。因此，我们的努力集中在显微镜方法的优化上，以了解神经元内部的分子如何响应和翻译神经元的电活动。