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Unraveling connections between the brain and gut

Posted on June 24, 2023

The brain and the digestive tract are in constant communication, relaying signals that help to control feeding and other behaviors. This extensive communication network also influences our mental state and has been implicated in many neurological disorders.

MIT engineers have designed a new technology for probing those connections. Using fibers embedded with a variety of sensors, as well as light sources for optogenetic stimulation, the researchers have shown that they can control neural circuits connecting the gut and the brain, in mice.

In a new study, the researchers demonstrated that they could induce feelings of fullness or reward-seeking behavior in mice by manipulating cells of the intestine. In future work, they hope to explore some of the correlations that have been observed between digestive health and neurological conditions such as autism and Parkinson’s disease.

The electronic interface that the researchers designed consists of flexible fibers that can carry out a variety of functions and can be inserted into the organs of interest. To create the fibers, the researcher used a technique called thermal drawing, which allowed him to create polymer filaments, about as thin as a human hair, that can be embedded with electrodes and temperature sensors.

The filaments also carry microscale light-emitting devices that can be used to optogenetically stimulate cells, and microfluidic channels that can be used to deliver drugs.

The mechanical properties of the fibers can be tailored for use in different parts of the body. For the brain, the researchers created stiffer fibers that could be threaded deep into the brain. For digestive organs such as the intestine, they designed more delicate rubbery fibers that do not damage the lining of the organs but are still sturdy enough to withstand the harsh environment of the digestive tract.

The fibers are also designed so that they can be controlled wirelessly, using an external control circuit that can be temporarily affixed to the animal during an experiment.

Using this interface, the researchers performed a series of experiments to show that they could influence behavior through manipulation of the gut as well as the brain.

First, they used the fibers to deliver optogenetic stimulation to a part of the brain called the ventral tegmental area (VTA), which releases dopamine. They placed mice in a cage with three chambers, and when the mice entered one particular chamber, the researchers activated the dopamine neurons. The resulting dopamine burst made the mice more likely to return to that chamber in search of the dopamine reward.

Then, the researchers tried to see if they could also induce that reward-seeking behavior by influencing the gut. To do that, they used fibers in the gut to release sucrose, which also activated dopamine release in the brain and prompted the animals to seek out the chamber they were in when sucrose was delivered.

Next, working with colleagues from Duke University, the researchers found they could induce the same reward-seeking behavior by skipping the sucrose and optogenetically stimulating nerve endings in the gut that provide input to the vagus nerve, which controls digestion and other bodily functions.

The researchers now plan to use this interface to study neurological conditions that are believed to have a gut-brain connection. For instance, studies have shown that autistic children are far more likely than their peers to be diagnosed with GI dysfunction, while anxiety and irritable bowel syndrome share genetic risks.

News Source: MIT

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