Decoding vagal firing patterns in gut to brain signalling

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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.