Axonic Neurotransmission In Neural Circuit Formation And Function

神经回路形成和功能中的轴突神经传递

• 批准号: EP/Y024311/1
• 负责人: Rafael Almeida
• 金额: $ 161.61万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY024311%2F1
• 关键词: Axonic; Neurotransmission; Neural; Circuit; Formation

This project will be the first in-depth in vivo examination of the hypothesis that axonic neurotransmission is a fundamental mode of cellular communication and neuronal circuit regulation using zebrafish as a model organism.A key goal in neuroscience is to understand how behaviour emerges from neurotransmission between brain cells. That neurons communicate at synapses using neurotransmitters is well known. But neurons also secrete neurotransmitters away from synapses, and how this occurs and impacts associated cells is, by contrast, poorly understood. My live-imaging studies of neurotransmitter release in individual zebrafish neurons revealed extensive axonic neurotransmission, whereby neurons release neurotransmitters along their axons, away from synapses. This was as frequent as synaptic release, which begs the questions of how axonic neurotransmission occurs and what purposes it serves. Unlike transmission at discrete synaptic sites, axon-released neurotransmitters can potentially diffuse broadly and reach many neurons and glia - now appreciated as active participants in circuit function. The impact of axon-released neurotransmitters in vivo is poorly understood because it has not been examined in a model in which it can be easily visualized and manipulated. Therefore, it remains unclear whether axonic transmission is a specialized mechanism that neurons employ to regulate circuit function in certain conditions.I will now undertake the ambitious task of examining the full impact of axon-released neurotransmitters in vivo. To do this, I will exploit the amenability of zebrafish for live imaging and the genetic toolkit I developed to elucidate mechanisms of axonic transmission, the elicited responses in target cells, and its effects on circuit function and behaviour. AxonicTransmission will provide key insights into the fundamental principles of cellular communication in the nervous system.

这个项目将是第一个深入的活体研究假设，轴突神经传递是一个基本的模式，细胞通信和神经元电路调节使用斑马鱼作为一个模型organis.A神经科学的一个关键目标是了解行为如何出现从脑细胞之间的神经传递。众所周知，神经元通过神经递质在突触上进行交流。但是神经元也会分泌远离突触的神经递质，相比之下，人们对这种情况如何发生以及如何影响相关细胞知之甚少。我对单个斑马鱼神经元中神经递质释放的实时成像研究揭示了广泛的轴突神经传递，神经元沿着它们的轴突释放神经递质，远离突触。这就像突触释放一样频繁，这就引出了轴突神经传递如何发生以及它起什么作用的问题。与离散突触部位的传递不同，轴突释放的神经递质可能广泛扩散并到达许多神经元和神经胶质-现在被认为是电路功能的积极参与者。轴突释放的神经递质在体内的影响知之甚少，因为它还没有在一个模型中，它可以很容易地可视化和操纵检查。因此，轴突传递是否是神经元在特定条件下调节回路功能的一种特殊机制仍不清楚。我现在将承担一项雄心勃勃的任务，研究轴突释放的神经递质在体内的全部影响。为此，我将利用斑马鱼的顺从性进行实时成像，并开发遗传工具包来阐明轴突传递的机制，在靶细胞中引起的反应及其对电路功能和行为的影响。AxonicTransmission将为神经系统中细胞通信的基本原理提供关键见解。