Mind-Blowing Breakthrough: MIT Engineers Unveil Game-Changing Tech to Control Hunger, Mood, and Defeat Diseases!

MIT engineers have now designed a new technology that can be used to test 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 the neural circuitry connecting the gut and brain in mice.

In a new study, researchers showed that they could induce feelings of satiety or reward-seeking behavior in mice by manipulating cells in the gut. 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.

“What’s exciting here is that we now have technology that can drive gut function and behaviors like eating. More importantly, we have the ability to start accessing the crosstalk between the gut and the brain with the millisecond precision of optogenetics, and we can do it in behavioral animals,” says Polina Anikeeva, the Matoula S. Salapatas Professor of Materials Science and Engineering, professor of brain and cognitive sciences, associate director of the MIT Electronics Research Laboratory, and a member of the McGovern Institute for MIT Brain Research. .

Anikeeva is the lead author of the new study, which appears today in Nature Biotechnology. The paper’s lead authors are MIT graduate student Atharva Sahasrabudhe, Duke University postdoc Laura Rupprecht, MIT postdoc Sirma Orguc, and MIT former postdoc Tural Khudiyev.

The brain-body connection

Last year, the McGovern Institute launched the K. Lisa Yang Brain-Body Center to study the interaction between the brain and other organs in the body. Research at the center focuses on illuminating how these interactions help shape behavior and overall health, with the goal of developing future therapies for a variety of diseases.

“There is continuous two-way crosstalk between the body and the brain,” says Anikeeva. “For a long time, we thought of the brain as a tyrant that sends information to the organs and controls everything. But now we know that there is a huge amount of feedback in the brain, and this feedback potentially controls some of the functions that we have.” have previously been attributed exclusively to central neural control.

Anikeeva, who runs the new center, was interested in investigating the signals that pass between the brain and the nervous system in the gut, also called the enteric nervous system. Sensory cells in the gut influence hunger and satiety through neural communication and hormone release.

Disentangling those hormonal and neural effects has been difficult because there hasn’t been a good way to quickly measure neural signals, which occur in milliseconds.

“To be able to perform gut optogenetics and then measure the effects on brain function and behavior, which requires millisecond precision, we needed a device that didn’t exist. So we decided to make it,” says Sahasrabudhe, who led the development. of intestinal and brain probes.

The electronic interface that the researchers designed consists of flexible fibers that can carry out a variety of functions and can be inserted into organs of interest. To create the fibers, Sahasrabudhe used a technique called thermal drawing, which allowed him to create polymer filaments, 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 like the intestine, they engineered more delicate rubbery fibers that don’t damage the lining of the organs but are tough enough to withstand the harsh environment of the digestive tract.

“To study the interaction between the brain and the body, it is necessary to develop technologies that can interact with the organs of interest and the brain at the same time, while recording physiological signals with a high signal-to-noise ratio,” Sahasrabudhe said. says. “We also need to be able to selectively stimulate different cell types in both organs in mice so that we can test their behaviors and perform causal analyzes of these circuits.”

The fibers are also designed so that they can be controlled wirelessly, using an external control circuit that can be temporarily attached to the animal during an experiment. This wireless control circuit was developed by Orguc, Schmidt Science Fellow, and Harrison Allen ’20, MEng ’22, who were co-advisors between the lab of Anikeeva and the lab of Anantha Chandrakasan, dean of the MIT School of Engineering and Vannevar Bush. Professor of Electrical and Computer Engineering.

driving behavior

Using this interface, the researchers ran a series of experiments to show that they could influence behavior through manipulation of the gut and 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 a particular chamber, the researchers activated dopamine neurons. The resulting dopamine burst made the mice more likely to return to that chamber in search of the dopamine reward.

The researchers then 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 triggered the release of dopamine in the brain and prompted the animals to seek the chamber they were in when the sucrose was delivered.

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

“Again, we got this place preference behavior that people have previously seen with stimulation in the brain, but now we’re not touching the brain. We’re just stimulating the gut and looking at control of central function from the periphery,” Anikeeva . she says.

Sahasrabudhe worked closely with Rupprecht, a postdoc in Professor Diego Bohorquez’s group at Duke, to test the ability of fibers to control feeding behaviors. They found that the devices could optogenetically stimulate cells that produce cholecystokinin, a hormone that promotes satiety. When this release of hormones was activated, the animals’ appetite was suppressed, even though they had been fasting for several hours. The researchers also demonstrated a similar effect when they stimulated cells that produce a peptide called PYY, which normally curbs appetite after consuming very rich foods.

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

“Now we can start to ask, are those coincidences or is there a gut-brain connection? And maybe there’s an opportunity for us to tap into those gut-brain circuits to start managing some of those conditions by manipulating the periphery.” “. circuits in a way that doesn’t directly ‘touch’ the brain and is less invasive,” says Anikeeva.