Decoding vagal firing patterns in gut to brain signalling

在动物中，感觉迷走神经是一种重要的神经，它向大脑发送关于内部器官的信息，特别是关于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。许多这样的物质(情绪物质)对脑神经细胞有影响，可以通过不同的方式改变情绪和行为。有些情绪物质可以是抗抑郁或抗焦虑的，而另一些则可能起到相反的作用。尽管这种肠道与大脑的连接很重要，但迷走神经如何编码从肠道传来的感觉信号仍然是一个谜。为了破解这个密码，我将使用体外准备(在玻璃盘子上进行实验)，用它我可以监听迷走神经从小鼠肠道短段带走的电信号。电脉冲的模式将根据它们平均出现的频率、它们是否以脉冲串的形式出现、脉冲串之间的时间间隔、脉冲串的持续时间以及它们在脉冲串中的出现频率来分析。我认为，摄入对大脑和行为有特殊影响的情绪物质具有特定的迷走神经代码，以识别该物质和对大脑的影响。然后，我将在给动物喂食一种单一情绪物质14天后，通过重复体外实验来研究长期摄入的影响。我还建议测试不同情绪物质的量(浓度)和给药时间对测量的迷走神经代码的影响，以及这与对情绪和行为的影响是如何关联的。通过破解迷走神经如何影响动物在日常生活中的情绪和行为的密码，这个项目的成功将极大地增加我们对肠道到大脑沟通的理解。这也将帮助我们确定改善情绪的新物质或营养物质，从而提高农业动物在长途运输或禁闭等环境压力下的韧性。除了本提案的最初5年之外，识别抗抑郁药物、改善情绪的迷走神经代码可能有助于我们开发和编程当前的脉冲参数，以便更有效地改变情绪迷走神经刺激设备，从畜牧业到人类健康都广泛使用。从长远来看，我们还将寻求识别与食欲和疼痛肠道刺激情绪成分变化相关的其他迷走神经编码--这些区域的感觉迷走神经功能也已被牵连。

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.