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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742696
• 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，感觉迷走神经是一条重要的神经，它向大脑传递有关内脏器官的信息，特别是有关被吞咽进入肠道的物质（如微生物、食物、脂肪酸和药物）的信息。许多这类物质（情绪物质）对脑神经细胞有影响，可以以不同的方式改变情绪和行为。一些情绪物质可以抗抑郁或抗焦虑，而其他物质可能有相反的效果。尽管肠道对大脑连接很重要，但迷走神经如何编码来自肠道的感觉信号仍然是一个谜。为了破解这个密码，我将使用一种体外（在一个玻璃盘子上实验）的装置，通过它我可以听到迷走神经从老鼠肠道的一小段带走的电信号。电脉冲的模式将根据它们平均发生的频率、它们是否在爆发中发生、爆发之间的时间间隔、爆发的持续时间以及它们在爆发中发生的频率来分析。我认为，摄入的对大脑和行为有特殊影响的情绪物质有一个特定的迷走神经密码，可以识别物质和对大脑的影响。然后，我将在动物喂食单一情绪物质14天后，通过重复体外实验来研究长期消费的影响。我还建议测试改变情绪物质的数量（浓度）和给药时间对测量的迷走神经代码的影响，以及这与情绪和行为的影响之间的关系。通过破解迷走神经在日常生活中如何影响动物情绪和行为的密码，这个项目的成功将大大增加我们对肠道与大脑沟通的理解。这也将帮助我们确定新的物质或营养物质，改善情绪，从而增加农业动物在长途运输或禁闭等环境压力下的恢复能力。在本建议的最初5年之后，确定抗抑郁药、改善情绪的迷走神经编码可能有助于我们开发和编程当前的脉冲参数，以更有效地改变情绪的迷走神经刺激装置，广泛应用于畜牧业和人类健康。从长远来看，我们还将寻找其他迷走神经编码，这些编码与食欲和肠道疼痛刺激的情绪成分的改变有关——感觉迷走神经功能也与这些区域有关。