Many behaviors, such as feeding, mental state, and even some neurological disorders are controlled by an extensive communication network, relaying signals between the brain and digestive tract. However, the technology necessary to understand this “brain–viscera interoceptive signaling” is limited.
Now, a new technology that is a multifunctional neural interface can be used to probe 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.
This work is published in Nature Biotechnology in the paper, “Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits.”
“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,” said Polina Anikeeva, PhD, professor in materials science and engineering at MIT and a member of MIT’s McGovern Institute for Brain Research.
“There’s continuous, bidirectional crosstalk between the body and the brain,” Anikeeva said. “For a long time, we thought that the brain is a tyrant that sends output into the organs and controls everything. But now we know that 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.”
Anikeeva was interested in probing the signals that pass between the brain and the nervous system of the gut. Sensory cells in the gut influence hunger and satiety via both neuronal communication and hormone release.
The electronic interface 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, Atharva Sahasrabudhe, a graduate student at MIT, used 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. The fibers are also designed so that they can be controlled wirelessly, using an external control circuit that can be temporarily affixed to the animal during an experiment.
Using this interface, the researchers performed a series of experiments to show that they could influence behavior through manipulation of the gut as well as the brain.
First, they used the fibers to deliver optogenetic stimulation to the ventral tegmental area (VTA) of the brain, which releases dopamine. They placed mice in a cage with three chambers, and when the mice entered one particular chamber, the researchers activated the dopamine neurons. The resulting dopamine burst made the mice more likely to return to that chamber in search of the dopamine reward.
Then, the researchers tried to see if they could also induce that reward-seeking behavior by influencing the gut. To do that, they used fibers in the gut to release sucrose, which also activated dopamine release in the brain and prompted the animals to seek out the chamber they were in when sucrose was delivered.
Next, the researchers found 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 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,” Anikeeva says.
The researchers found that the devices could optogenetically stimulate cells that produce cholecystokinin, a hormone that promotes satiety. When this hormone release was activated, the animals’ appetites were 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 very rich foods are consumed.
The researchers plan to use this interface to study neurological conditions that are believed to have a gut-brain connection. For instance, studies have shown that children with autism are far more likely than their peers to be diagnosed with GI dysfunction, while anxiety and irritable bowel syndrome share genetic risks.
“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.