Decoding vagal firing patterns in gut to brain signalling

点击翻译按钮获取中文摘要

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.