MIT’s Latest Breakthrough: Investigating Neural Circuits That Impact Hunger, Mood, and Diseases

Engineers at MIT have pioneered a cutting-edge technology to examine the intricate relationship between the brain and the digestive system. By employing fibers embedded with light sources and sensors for optogenetic stimulation, they have successfully demonstrated its potential in mice. Manipulating intestinal cells led to sensations of satiety or reward-driven behavior. This breakthrough presents new opportunities to explore the connection between digestive well-being and neurological disorders like autism and Parkinson’s disease.

Understanding the Link Between the Brain and the Gut

MIT engineers have developed an innovative optogenetic technology capable of manipulating the neurological connections between the brain and the gut. This breakthrough holds promise in unraveling the correlation between digestive health and neurological conditions.

Constant communication occurs between the brain and the digestive tract, transmitting signals that regulate feeding habits and other behaviors. This intricate network of communication also influences our mental state and plays a role in various neurological disorders.

To investigate these connections, MIT engineers devised a technology utilizing fibers embedded with diverse sensors and light sources. Through their research on mice, they demonstrated the ability to control neural circuits connecting the gut and the brain.

In their study, the researchers successfully induced sensations of satiety or reward-seeking behavior in mice by manipulating intestinal cells. Moving forward, they aim to delve into the observed associations between digestive health and neurological conditions like autism and Parkinson’s disease.

The innovative fibers embedded with sensors and light sources enable manipulation and monitoring of the connections between the brain and the digestive tract. (Image courtesy of the researchers)

Excitingly, Polina Anikeeva, the Matoula S. Salapatas Professor in Materials Science and Engineering, professor of brain and cognitive sciences, director of the K. Lisa Yang Brain-Body Center, associate director of MIT’s Research Laboratory of Electronics, and a member of MIT’s McGovern Institute for Brain Research, shared, “The exciting thing here is that we now have technology that can drive gut function and behaviors such as feeding. 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 behaving animals.”

Anikeeva is the senior author of the groundbreaking study, published in the journal Nature Biotechnology on June 22. The lead authors of the paper include Atharva Sahasrabudhe, an MIT graduate student, Laura Rupprecht, a postdoc from Duke University, Sirma Orguc, an MIT postdoc, and Tural Khudiyev, a former MIT postdoc.

The Brain-Body Connection

Last year, the McGovern Institute established the K. Lisa Yang Brain-Body Center to study the interplay between the brain and other organs in the body. The center’s research focuses on elucidating how these interactions shape behavior and overall health, with the ultimate goal of developing future therapies for various diseases.

“For a long time, we thought the brain is a tyrant that sends output into the organs and controls everything. But now we know there’s a lot of feedback back into the brain, and this feedback potentially controls some of the functions that we have previously attributed exclusively to the central neural control,” explained Anikeeva regarding the continuous bidirectional crosstalk between the brain and the body.

The team sought to investigate the signals exchanged between the brain and the enteric nervous system, which refers to the nervous system of the gut. Sensory cells in the gut influence hunger and satiety through both neuronal communication and hormone release.

Unraveling the effects of these hormonal and neural interactions has proven challenging due to the absence of a suitable method to rapidly measure neuronal signals, which occur within 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,” shared Sahasrabudhe, the driving force behind the development of the gut and brain probes.

The researchers created an electronic interface consisting of flexible fibers capable of fulfilling multiple functions and being inserted into targeted organs. Sahasrabudhe employed a technique called thermal drawing to produce polymer filaments as thin as a human hair, which could be embedded with electrodes and temperature sensors.

The filaments also contained microscale light-emitting devices for optogenetic stimulation and microfluidic channels for drug delivery.

The mechanical properties of the fibers were tailored to suit different body parts. For instance, stiffer fibers were designed for brain applications, enabling their insertion deep into the organ. Delicate, rubbery fibers were developed for digestive organs like the intestine, ensuring they wouldn’t harm the organ lining while withstanding the harsh digestive environment.

Sahasrabudhe elaborated, “To study the interaction between the brain and the body, it is necessary to develop technologies that can interface with organs of interest as well as the brain at the same time, while recording physiological signals with a high signal-to-noise ratio. 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 analyses of these circuits.”

Additionally, the fibers were designed for wireless control. An external control circuit, temporarily attached to the animal during an experiment, enabled wireless manipulation. This wireless control circuit was developed by Orguc, a Schmidt Science Fellow, and Harrison Allen ’20, MEng ’22, who were co-advised by the Anikeeva lab and the lab of Anantha Chandrakasan, dean of MIT’s School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science.

Driving Behavior

Utilizing this interface, the researchers conducted a series of experiments to demonstrate their ability to influence behavior by manipulating both the gut and the brain.

Initially, they employed the fibers to provide optogenetic stimulation to a brain region known as the ventral tegmental area (VTA), responsible for dopamine release. The mice were placed in a three-chambered enclosure, and upon entering a particular chamber, the researchers activated the dopamine neurons. The resulting dopamine surge increased the mice’s likelihood of returning to that chamber in search of the rewarding dopamine experience.

Next, the researchers sought to induce similar reward-seeking behavior by targeting the gut. They achieved this by using gut fibers to release sucrose, which also triggered dopamine release in the brain, prompting the animals to seek out the chamber where sucrose was administered.

Working alongside colleagues from Duke University, the researchers discovered that they could elicit the same reward-seeking behavior by bypassing sucrose and optogenetically stimulating nerve endings in the gut that provide input to the vagus nerve. The vagus nerve controls digestion and other bodily functions.

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

Sahasrabudhe collaborated closely with Rupprecht, a postdoc in Professor Diego Bohorquez’s group at Duke, to evaluate the fibers’ capacity to control feeding behaviors. They successfully demonstrated that the devices could optogenetically stimulate cells producing cholecystokinin, a hormone that promotes satiety. Activation of this hormone suppressed the animals’ appetites, even after hours of fasting. The researchers also replicated a similar effect by stimulating cells producing a peptide called PYY, which typically reduces appetite after consuming rich foods.

Moving forward, the researchers intend

Frequently Asked Questions (FAQs) about gut-brain connections

More about gut-brain connections

• MIT News: New technology can probe the neural circuits that influence hunger, mood, and diseases
• Research paper in Nature Biotechnology: Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits