MIT engineers have actually established an innovation to study the interplay in between the brain and gastrointestinal system by using fibers embedded with sensors and light sources for optogenetic stimulation. “For a long time, we thought the brain is a tyrant that sends output into the controls and organs everything. Now we understand theres a lot of feedback back into the brain, and this feedback potentially manages some of the functions that we have actually formerly attributed solely to the central neural control.”
For the brain, the researchers created stiffer fibers that might be threaded deep into the brain. They used the fibers to provide optogenetic stimulation to a part of the brain called the ventral tegmental area (VTA), which launches dopamine.
In a new research study, the scientists showed that they might cause sensations of fullness or reward-seeking habits in mice by manipulating cells of the intestinal tract. In future work, they intend to explore a few of the connections that have been observed in between digestion health and neurological conditions such as autism and Parkinsons disease.
These flexible fibers, which are embedded with sensing units and lights, can be utilized to manipulate and monitor the connections in between the brain and the gastrointestinal tract. Credit: Courtesy of the scientists
” The amazing thing here is that we now have technology that can drive gut function and behaviors such as feeding. We have the capability to start accessing the crosstalk in between the gut and the brain with the millisecond precision of optogenetics, and we can do it in behaving animals,” states Polina Anikeeva, the Matoula S. Salapatas Professor in Materials Science and Engineering, a professor of brain and cognitive sciences, director of the K. Lisa Yang Brain-Body Center, associate director of MITs Research Laboratory of Electronics, and a member of MITs McGovern Institute for Brain Research.
Anikeeva is the senior author of the new research study, which was published on June 22 in the journal Nature Biotechnology. The papers lead authors are MIT graduate trainee Atharva Sahasrabudhe, Duke University postdoc Laura Rupprecht, MIT postdoc Sirma Orguc, and previous MIT postdoc Tural Khudiyev.
The brain-body connection
In 2015, the McGovern Institute released the K. Lisa Yang Brain-Body Center to study the interplay between the brain and other organs of the body. Research at the center focuses on illuminating how these interactions help to shape behavior and general health, with an objective of developing future treatments for a range of illness.
” Theres continuous, bidirectional crosstalk between the body and the brain,” Anikeeva states. “For a long period of time, we believed the brain is a tyrant that sends output into the controls and organs whatever. However now we know theres a great deal of feedback back into the brain, and this feedback possibly manages a few of the functions that we have actually previously attributed solely to the main neural control.”
Duke University postdoc Laura Rupprecht, MIT graduate trainee Atharva Sahasrabudhe, and MIT postdoc Sirma Orguc in the laboratory. Credit: Courtesy of the researchers
As part of the centers work, Anikeeva set out to probe the signals that pass in between the brain and the nerve system of the gut, likewise called the enteric nervous system. Sensory cells in the gut impact appetite and satiety by means of both the neuronal communication and hormonal agent release.
Untangling those hormonal and neural results has been challenging since there hasnt been a great way to quickly measure the neuronal signals, which occur within milliseconds.
” To be able to carry out gut optogenetics and after that determine the effects on brain function and behavior, which requires millisecond accuracy, we required a device that didnt exist. We decided to make it,” says Sahasrabudhe, who led the advancement of the gut and brain probes.
The electronic user interface that the researchers developed consists of versatile fibers that can perform a range of functions and can be inserted into the organs of interest. To produce the fibers, Sahasrabudhe utilized a technique called thermal illustration, which enabled him to create polymer filaments, about as thin as a human hair, that can be embedded with electrodes and temperature sensing units.
The filaments also bring microscale light-emitting devices that can be utilized to optogenetically stimulate cells, and microfluidic channels that can be used to provide drugs.
The mechanical properties of the fibers can be customized for use in different parts of the body. For the brain, the scientists developed stiffer fibers that might be threaded deep into the brain. For digestive organs such as the intestine, they developed more delicate rubbery fibers that do not damage the lining of the organs but are still tough enough to withstand the harsh environment of the gastrointestinal system.
” To study the interaction between the body and the brain, it is necessary to establish innovations that can user interface with organs of interest in addition to the brain at the very same time, while taping physiological signals with high signal-to-noise ratio,” Sahasrabudhe states. “We likewise need to be able to selectively promote different cell key ins both organs in mice so that we can evaluate their behaviors and perform causal analyses of these circuits.”
The fibers are also designed so that they can be controlled wirelessly, utilizing an external control circuit that can be temporarily attached to the animal throughout an experiment. This wireless control circuit was developed by Orguc, a Schmidt Science Fellow, and Harrison Allen 20, MEng 22, who were co-advised between the Anikeeva lab and the laboratory of Anantha Chandrakasan, dean of MITs School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science.
Driving habits
Using this interface, the scientists carried out a series of experiments to show that they could influence habits through manipulation of the gut along with the brain.
First, they utilized the fibers to deliver optogenetic stimulation to a part of the brain called the forward tegmental location (VTA), which releases dopamine. They positioned mice in a cage with 3 chambers, and when the mice went into one particular chamber, the scientists triggered the dopamine neurons. The resulting dopamine burst made the mice more likely to return to that chamber in search of the dopamine reward.
The scientists tried to see if they could likewise induce that reward-seeking habits by influencing the gut. To do that, they used fibers in the gut to release sucrose, which likewise triggered dopamine release in the brain and triggered the animals to look for out the chamber they remained in when sucrose was provided.
Next, working with colleagues from Duke University, the scientists discovered they might cause the very same reward-seeking behavior by avoiding the sucrose and optogenetically promoting nerve endings in the gut that provide input to the vagus nerve, which manages food digestion and other bodily functions.
” Again, we got this place choice 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,” Anikeeva says.
Sahasrabudhe worked closely with Rupprecht, a postdoc in Professor Diego Bohorquez group at Duke, to check the fibers ability to manage feeding habits. They found that the devices might optogenetically stimulate cells that produce cholecystokinin, a hormonal agent that promotes satiety. When this hormonal agent release was triggered, the animals hungers were reduced, despite the fact that they had actually been fasting for several hours. The scientists likewise showed a similar effect when they promoted cells that produce a peptide called PYY, which usually curbs appetite after really rich foods are taken in.
The researchers now plan to utilize this user interface to study neurological conditions that are believed to have a gut-brain connection. Research studies have shown that autistic children are far more most likely than their peers to be identified with GI dysfunction, while anxiety and irritable bowel syndrome share genetic risks.
” We can now start asking, are those coincidences, or exists a connection in between the brain and the gut? And perhaps there is an opportunity for us to take advantage of those gut-brain circuits to begin handling some of those conditions by controling the peripheral circuits in such a way that does not directly touch the brain and is less invasive,” Anikeeva states.
Referral: “Multifunctional microelectronic fibers make it possible for wireless modulation of gut and brain neural circuits” by Atharva Sahasrabudhe, Laura E. Rupprecht, Sirma Orguc, Tural Khudiyev, Tomo Tanaka, Joanna Sands, Weikun Zhu, Anthony Tabet, Marie Manthey, Harrison Allen, Gabriel Loke, Marc-Joseph Antonini, Dekel Rosenfeld, Jimin Park, Indie C. Garwood, Wei Yan, Farnaz Niroui, Yoel Fink, Anantha Chandrakasan, Diego V. Bohórquez and Polina Anikeeva, 22 June 2023, Nature Biotechnology.DOI: 10.1038/ s41587-023-01833-5.
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, the National Institute of Neurological Disorders and Stroke, the National Science Foundation (NSF) Center for Materials Science and Engineering, the NSF Center for Neurotechnology, the National Center for Complementary and Integrative Health, a National Institutes of Health Directors Pioneer Award, the National Institute of Mental Health, and the National Institute of Diabetes and Digestive and Kidney Diseases.
MIT engineers have actually developed a technology to study the interaction in between the brain and digestion system by using fibers embedded with sensing units and source of lights for optogenetic stimulation. The technology has been demonstrated in mice, where adjustment of cells in the intestinal tract resulted in feelings of fullness or reward-seeking habits. This opens new possibilities for checking out the link in between digestive health and neurological conditions such as autism and Parkinsons disease.
Deciphering Connections Between the Brain and Gut
MIT engineers have actually established a brand-new optogenetic innovation that can manipulate the neurological connections in between the brain and gut, potentially providing insights into the links between gastrointestinal health and neurological conditions.
The brain and the gastrointestinal system are in constant communication, relaying signals that help to manage feeding and other behaviors. This extensive communication network likewise influences our frame of mind and has been linked in lots of neurological disorders.
MIT engineers have actually developed a brand-new technology for penetrating those connections. Using fibers embedded with a range of sensing units, along with source of lights for optogenetic stimulation, the researchers have shown that they can manage neural circuits linking the gut and the brain, in mice.
