Decoding vagal firing patterns in gut to brain signalling

解码肠道迷走神经放电模式到大脑的信号传导

• 批准号: RGPIN-2021-03816
• 负责人: Kunze, Wolfgang
• 金额: $ 2.62万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763686
• 关键词: Decoding; vagal; firing; patterns; gut

In animals the sensory vagus is an important nerve that sends information about the internal organs to the brain, and in particular about substances (e.g. microbes, foods, fatty acids and drugs) that have been swallowed to enter the intestine. Many such substances (mood substances) have effects on brain nerve cells that can alter mood and behaviour in different ways. Some mood substances can be antidepressant or antianxiety while others may have opposite effects. Despite the importance of this gut to brain connection, how the vagus codes sensory signals that travel from the gut remains a mystery. To break this code, I will use an out of the body (experiment on a glass dish) preparation with which I can listen in to electrical signals that the vagus nerve carries away from short segments of mouse intestine. The patterns of electrical impulses will be analysed according to how frequently they occur on average, whether they occur in bursts, the time intervals between bursts, the duration of the bursts and how frequently they occur within bursts. I propose that ingested mood substances that have a particular effect on the brain and behaviour have a specific vagal code that identifies the substance and the effect on the brain. I will then study the effects of longer term consumption by repeating the in vitro experiments after the animals have been fed with a single mood substance for 14 days. I also propose to test the effects of varying the amount (concentrations) of the mood substances and the timing of the administration on the measured vagal code and how this correlates with effects on mood and behaviour. Success in this program will greatly increase our understanding of gut to brain communication by cracking the code for how the vagus could influence animal mood and behaviour in daily life. This will also help us identify new substances or nutrients that improve mood and thus increase resilience in animals in agriculture subject to environmental stress such as long haul transportation or confinement. Beyond the initial 5 years of the present proposal, identification of antidepressant, mood improving vagal codes may help us to develop and program current pulse parameters for more effective mood altering vagal nerve stimulus devices broadly useful from animal husbandry to human health. In the longer term we will also seek to identify other vagal codes related to appetite and alteration in the emotional component of painful intestinal stimuli-areas for which sensory vagal nerve function has also been implicated.

在动物中，感觉迷走神经是一种重要的神经，将有关内部器官的信息发送到大脑，尤其是有关已吞噬进入肠道的物质（例如微生物，食物，脂肪酸和药物）的物质（例如微生物，食物，脂肪酸和药物）。许多这样的物质（情绪物质）对脑神经细胞具有影响，可以以不同的方式改变情绪和行为。某些情绪物质可能是抗抑郁药或抗焦虑，而另一些可能具有相反的影响。尽管这种肠道对大脑连接的重要性很重要，但迷走神经代码如何从肠道传播的感觉信号仍然是一个谜。为了打破此代码，我将使用一个从体内（玻璃盘上的实验）制备的准备，我可以听到迷走神经远离鼠标肠的短段的电信号。电脉冲的模式将根据平均发生的频率进行分析，无论它们是出现在突发中，爆发之间的时间间隔，爆发的持续时间以及它们在突发中发生的频率。我建议摄取对大脑和行为具有特殊影响的情绪物质具有特定的迷走神经代码，可识别物质和对大脑的影响。然后，我将通过在动物被单个情绪物质喂养14天后重复体外实验来研究长期消耗的影响。我还建议测试改变情绪物质的数量（浓度）的影响以及管理对所测量迷走神经代码的影响，以及这与情绪和行为的影响如何相关。该计划的成功将大大提高我们对肠道对大脑沟通的理解，从而破解迷走神经如何影响日常生活中的动物情绪和行为的代码。这也将帮助我们确定改善情绪的新物质或营养，从而提高农业动物的弹性，但会受到环境压力，例如长期运输或限制。除了本提案的最初5年之外，对抗抑郁药的识别，改善迷走神经代码的情绪可能有助于我们开发和编程当前的脉冲参数，以更有效地改变迷走神经刺激设备，从而从畜牧业到人类健康广泛有用。从长远来看，我们还将寻求确定与食欲有关的其他迷走神经代码，并改变了痛苦的肠道刺激疗法的情绪成分，也涉及感官迷走神经功能。