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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 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,” says Polina Anikeeva, a professor of brain and cognitive sciences, and associate director of MIT’s Research Laboratory of Electronics, and a member of MIT’s McGovern Institute for Brain Research. Anikeeva is also the senior author of the new study, which is published in Nature Biotechnology.
Last year, the McGovern Institute launched 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 overall health, with a goal of developing future therapies for a variety of diseases.
“There’s continuous, bidirectional crosstalk between the body and the brain,” Anikeeva says. “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 into the brain, and this potentially controls some of the functions that we have previously attributed exclusively to the central neural control.”
As part of the center’s work, Anikeeva set out to probe 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 via both the neuronal communication and hormone release.
Untangling those hormonal and neural effects has been difficult because there hasn’t been a good way to rapidly measure the 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,” says MIT graduate student Atharva Sahasrabudhe, who led the development of the gut and brain probes and is one of the paper’s lead authors.
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, Sahasrabudhe 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.
“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 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 behaviors and perform causal analyses of these circuits.”
The researchers now plan to use the interface they developed 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.