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-2019-05982
• 负责人: Kunze, Wolfgang
• 金额: $ 2.33万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684222
• 关键词: Decoding; vagal; firing; patterns; gut

Decoding vagal firing patterns in gut to brain signalling.***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) 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 that different mood substances that stimulate the vagus nerve but have opposite effects on behaviour and the brain will activate differing brain regions or have opposing effects on the brain regions. After feeding the substances, I will measure brain activity using a validated marker for brain neuron activation (cFos) in brain sections taken once the mice have been killed at the end of the experiment.***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. Ultimately, identification of antidepressant, mood improving vagal codes may help develop and program current pulse parameters for vagal nerve stimulus devices broadly useful from animal husbandry to human health.

在肠道中解码迷走神经的发射模式。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，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。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食14天后重复体外实验来研究长期消耗的影响。喂食物质后，我将使用经过验证的脑神经元激活标记（CFO）测量大脑活动，一旦在实验结束时杀死小鼠。***在该程序中的成功将大大提高我们对肠道通信的理解，从而通过如何在日常生活中影响动物的情绪和行为来破解对动物的情绪和行为的破解。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。最终，鉴定抗抑郁药，改善迷走神经代码的情绪可能有助于开发和编程迷走神经刺激设备的当前脉冲参数，从动物畜牧业到人类健康广泛有用。