Summary: Researchers have created technology that allows them to probe and control neural circuits between the gut and the brain, demonstrating their ability to influence satiety or reward-seeking behavior in mice.
The interface uses flexible fibers embedded with sensors, temperature sensors and light sources for optogenetic stimulation. The goal is to use this technology to study the links between digestive health and neurological conditions such as autism and Parkinson’s disease.
This work reveals the potential to manage these conditions by manipulating peripheral circuits in a noninvasive manner.
Key facts:
- MIT researchers have developed technology that uses sensor-embedded fibers to control the neural circuits between the gut and the brain that affect feeding behavior in mice.
- This technology may offer insights into the relationship between digestive health and neurological conditions such as autism and Parkinson’s disease.
- The research holds promise for managing neurological conditions in a non-invasive manner by manipulating peripheral circuits.
The brain and digestive tract are in constant communication, transmitting signals that help control eating and other behaviors. This extensive communication network also affects our mental state and is implicated in many neurological disorders.
MIT engineers have now designed a new technology that can be used to study these connections.
Using fibers embedded with various sensors as well as light sources for optogenetic stimulation, researchers have shown that they can control the neural circuits connecting the gut and brain in mice.
In a new study, researchers have demonstrated that they can induce satiety or reward-seeking behavior in mice by manipulating gut cells.
In future work, they hope to explore some of the correlations seen between digestive health and neurological conditions such as autism and Parkinson’s disease.
“The exciting thing here is that we now have technology that can manage gut function and behaviors like eating. More importantly, we have the ability to start accessing the cross-talk between the gut and the brain with the millisecond precision of optogenetics, and we can do it in behaving animals,” says Polina Anikeeva, Matoula S Professor of Materials Science and Engineering Salapatas, professor of brain and cognitive sciences, associate director of the MIT Electronics Research Laboratory and member of the MIT McGovern Institute for Brain Research.
Anikeeva is the lead author of the new study, which appears today in Natural Biotechnologies. The paper’s lead authors are MIT graduate student Atharva Sahasrabudhe, Duke University postdoc Laura Rupprecht, MIT postdoc Sirma Orguk, and former MIT postdoc Tural Khudiev.
The brain-body connection
Last year, the McGovern Institute launched the K. Lisa Yang Center for Brain and Body to study the interaction between the brain and other organs of the body. Research at the center focuses on elucidating how these interactions help shape behavior and overall health, with the goal of developing future therapies for various diseases.
“There is a constant two-way interaction between the body and the brain,” says Anikeeva.
“For a long time we thought that the brain was a tyrant that sent information to the organs and controlled everything. But we now know that there is a lot of feedback back into the brain, and this feedback potentially controls some of the functions that we previously attributed exclusively to central nervous control.
Anikeeva, who directs the new center, was interested in studying the signals that pass between the brain and the nervous system of the gut, also called the enteric nervous system.
Sensory cells in the gut influence hunger and satiety through both neural communication and hormone release.
Disentangling these hormonal and neural effects has been difficult because there has not been a good way to rapidly measure neural signals that occur within milliseconds.
“To be able to do 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 do it,” says Sahasrabudhe, who led the development of the gut and brain probes.
The electronic interface the researchers are designing consists of flexible fibers that can perform various functions and can be inserted into the organs of interest.
To create the fibers, Sahasrabudhe used a technique called thermal drawing, which allows 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, researchers have created stiffer fibers that can be inserted deep into the brain.
For digestive organs like the intestines, they have designed more delicate rubber fibers that do not damage the lining of the organs, but are still strong enough to withstand the harsh environment of the digestive tract.
“In order to study the interaction between the brain and the body, it is necessary to develop technologies that can interact with the organs of interest as well as the brain simultaneously, recording physiological signals with a high signal-to-noise ratio,” Sahasrabudhe says.
“We also need to be able to selectively stimulate different cell types in both organs in mice so that we can test their behavior and perform causal analyzes of these circuits.”
The fibers are also designed to 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, a Schmidt research fellow, and Harrison Allen ’20, MEng ’22, who were co-advised between the Anikeeva lab and the lab of Anantha Chandrakasan, dean of the MIT School of Engineering and the Vannevar Bush Professor of electrical engineering and computer science.
Driving behavior
Using this interface, the researchers performed a series of experiments to show that they could influence behavior by manipulating 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 dopamine neurons.
The resulting dopamine rush made the mice more likely to return to that chamber in search of a dopamine reward.
The researchers then tried to see if they could also induce this reward-seeking behavior by affecting the gut. To do this, they used fiber in the gut to release sucrose, which also activated the release of dopamine in the brain and prompted the animals to seek out the chamber they were in when the sucrose was delivered.
Then, working with colleagues at Duke University, the researchers discovered 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.
“Again, we have this site preference that people have seen before with stimulation in the brain, but now we’re not touching the brain. We simply stimulate the intestines, and from the periphery we observe control over the central function,” says Anikeeva.
Sahasrabudhe worked closely with Rupprecht, a postdoctoral fellow in Professor Diego Bohorquez’s group at Duke, to test the fiber’s ability to control eating behavior. They discovered 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 eating very rich foods.
The researchers now plan to use this interface to study neurological conditions believed to have a connection between the gut and the brain. For example, studies show that children with autism are much more likely than their peers to be diagnosed with GI dysfunction, while anxiety and irritable bowel syndrome share genetic risks.
“Now we can start asking, are these coincidences or is there a connection between the gut and the brain?” And maybe there’s an opportunity to tap into those gut-brain circuits to start managing some of these conditions by manipulating the peripheral circuits in a way that doesn’t ‘touch’ the brain directly and is less invasive,” says Anikeeva.
Financing: The research was funded in part by the Hock E. Tan and K. Lisa Yang Center for Autism Research and the K. Lisa Yang Brain-Body Center at the McGovern Institute, National Institute of Neurological Disorders and Stroke, National Science Institute Center for Materials Science and Engineering Foundation (NSF), NSF Neurotechnology Center, National Center for Complementary and Integrative Health, National Institutes of Health Director’s Pioneer Award, National Institute of Mental Health, and National Institute of Diabetes and Digestive and Kidney Diseases.
About this gut-brain axis research news
Author: Sarah McDonnell
source: WITH
Contact: Sarah McDonnell-MIT
Image: Image credited to Neuroscience News
Original research: Free access.
“Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits” by Polina Anikeeva and others. Natural Biotechnologies
Summary
Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits
Progress in understanding brain and visceral interoceptive signaling has been hampered by the paucity of implantable devices suitable for studying the neurophysiology of both brain and peripheral organs during behavior.
Here, we describe multifunctional neural interfaces that combine the scalability and mechanical flexibility of thermally drawn polymer-based fibers with the complexity of microelectronic chips for organs as diverse as the brain and gut.
Our approach uses meter-long continuous fibers that can integrate light sources, electrodes, thermal sensors, and microfluidic channels in a miniaturized footprint. Combined with custom-made control modules, the fibers wirelessly deliver light for optogenetics and transfer data for physiological recording.
We validate this technology by modulating the mesolimbic reward pathway in the mouse brain. We then apply the fibers into the anatomically challenging intestinal lumen and demonstrate wireless control of the sensory epithelial cells that guide feeding behavior.
Finally, we show that optogenetic stimulation of vagal afferents from the intestinal lumen is sufficient to induce a reward phenotype in untethered mice.