These fibers could manipulate and monitor the connections between the brain and the digestive tract. [Image courtesy of the researchers]
Using fibers embedded with sensors, plus light sources for optogenetic stimulation, the researchers demonstrated this control in mice. The study showed that they could induce feelings of fullness or reward-seeking behavior by manipulating cells of the intestine. This could lead to the exploration of the correlations between digestive health and neurological conditions like 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,” Polina Anikeeva said in a post on the MIT website. Anikeeva serves as 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 MIT’s Research Laboratory of Electronics and a member of MIT’s McGovern Institute for Brain Research.
Anikeeva also authored the MIT study, which appeared in Nature Biotechnology. Lead authors include MIT graduate student Atharva Sahasrabudhe, Duke University postdoc Laura Rupprecht, MIT postdoc Sirma Orguc, and former MIT postdoc Tural Khudiyev.
The MIT team aimed to probe the signals that pass between the brain and the enteric nervous system — the nervous system of the gut. Sensory cells in the gut influence hunger and satiety by neuronal communication and hormone release. According to the team, it’s been historically difficult to work out the effects because there’s been no successful way of rapidly measuring 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,” said Sahasrabudhe. Sahasrabudhe led the development of the gut and brain probes.
How the engineers designed the probes connecting the brain and gut
The engineers designed an electronic interface comprised of flexible fibers capable of a range of functions, plus insertion into organs of interest. To create the fibers, they used thermal drawing, creating polymer filaments for embedding with electrodes and temperature sensors. Those filaments come in about as thin as a human hair, the researchers say.
MIT says the fibers also carry microscale, light-emitting devices that can optogenetically stimulate cells. Additionally, they carry microfluidic channels that could potentially deliver drugs.
Different parts of the body require different designs for the fibers, too. For the brain, the team created stiff fibers for deep threading. For digestive organs like the intestine, the design of the fibers was more delicate and rubbery so as to not damage the lining of the organs. However, they remain sturdy enough to withstand the environment of the digestive tract.
Finally, the team designed the fibers for wireless control capabilities through an external control circuit.
“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 said. “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.”
Putting it into practice
Using the developed interface, the researchers performed experiments to influence behavior by manipulating the gut and the brain. They first used the fibers to deliver optogenetic stimulation to the ventral tegmental area (VTA), which releases dopamine. After stimulation, they placed mice in a cage with three chambers. When they entered one specific chamber, the researchers activated the dopamine neurons. That proved to make the mice more likely to return to that chamber to seek out the dopamine reward.
Similarly, they tried to induce reward-seeking behavior by influencing the gut. They used fibers to release sucrose, which activated a dopamine release in the brain. That prompted the mice to seek the chamber in which they received a sucrose delivery.
Working with colleagues from Duke University, the team found they could induce the same behavior by skipping sucrose. Instead, they optogenetically stimulated nerve endings in the gut that provide input to the vagus nerve, which controls digestion. The team found their devices could optogenetically stimulate cells that produce cholecystokinin, a hormone that promotes satiety. This suppressed the appetite of the mice when the hormone release activated, despite several hours of fasting.
The team hopes to next use the interface to study neurological conditions believed to have a gut-brain connection.
“We can now begin asking, are those coincidences, or is there a connection between the gut and the brain? And maybe there is an opportunity for us to tap into those gut-brain circuits to begin managing some of those conditions by manipulating the peripheral circuits in a way that does not directly ‘touch’ the brain and is less invasive,” Anikeeva said.
