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，它将有关内部器官的信息发送到大脑，特别是有关已被吞咽进入肠道的物质（例如微生物，食物，脂肪酸和药物）的信息。许多这样的物质（情绪物质）对大脑神经细胞有影响，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，而其他物质可能具有相反的作用。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（在玻璃皿上做实验）准备，通过这种准备，我可以监听迷走神经从小鼠肠的一小段中带走的电信号。电脉冲的模式将根据它们平均发生的频率、它们是否以脉冲串的形式发生、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内发生的频率进行分析。我认为，摄入的情绪物质对大脑和行为有特殊的影响，有一个特定的迷走神经代码，识别物质和对大脑的影响。然后，我将通过重复体外实验来研究长期食用的影响，这些实验是在动物被喂食单一情绪物质14天后进行的。我还建议测试情绪物质的量（浓度）和给药时间对测量的迷走神经代码的影响，以及这与情绪和行为的影响如何相关。这项计划的成功将大大增加我们对肠道与大脑交流的理解，因为它破解了迷走神经如何影响动物日常生活中的情绪和行为的密码。这也将帮助我们确定新的物质或营养素，改善情绪，从而提高农业动物在长途运输或禁闭等环境压力下的适应力。在本提案的最初5年之后，抗抑郁剂、情绪改善迷走神经代码的识别可以帮助我们开发和编程电流脉冲参数，用于更有效的情绪改变迷走神经刺激装置，其从畜牧业到人类健康广泛有用。从长远来看，我们也将寻求确定其他迷走神经代码相关的食欲和改变的痛苦的肠刺激区的情感成分，其中感觉迷走神经功能也有牵连。

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.