The intricate communication network between the brain and the digestive tract plays a vital role in regulating feeding behaviors and mental states. Recent research has suggested its involvement in various neurological disorders. To explore these connections, engineers at MIT have introduced a novel technology that enables the manipulation of neural circuits linking the gut and the brain in mice. By utilizing specially designed fibers embedded with sensors and light sources for optogenetic stimulation, the researchers demonstrated their ability to induce sensations of fullness or reward-seeking behavior by manipulating intestinal cells.

The study, published in Nature Biotechnology, represents a significant advancement in understanding the interplay between the brain and other organs in the body. The researchers are particularly interested in exploring the correlations observed between digestive health and neurological conditions such as autism and Parkinson’s disease. Their breakthrough lies in the millisecond precision of optogenetics, allowing for the investigation of gut-brain interactions in behaving animals.

Professor Polina Anikeeva, a leading author of the study and director of the K. Lisa Yang Brain-Body Center at MIT, highlights the significance of the technology, stating, “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.”

The researchers focused on the enteric nervous system, the nervous system of the gut, which influences hunger, satiety, and hormone release. Previous attempts to understand the hormonal and neural effects faced challenges due to the lack of a rapid measurement technique for neuronal signals, which occur within milliseconds.

To overcome this limitation, the team developed an electronic interface comprising flexible fibers capable of various functions and suitable for insertion into specific organs. The fibers, created using thermal drawing, consist of polymer filaments as thin as a human hair, embedded with electrodes, temperature sensors, microscale light-emitting devices for optogenetic stimulation, and microfluidic channels for drug delivery.

The mechanical properties of the fibers are customized for different areas of the body. For brain-related studies, stiffer fibers enable deep insertion, while delicate and rubbery fibers designed for digestive organs prevent damage to the organ lining while withstanding the harsh digestive environment.

Wireless control of the fibers is achieved through an external control circuit, temporarily attached to the animal during experiments. The wireless control circuit allows for precise manipulation of the gut and brain, enabling the researchers to influence behavior effectively.

Using the fiber interface, the researchers conducted a series of experiments that demonstrated their ability to manipulate behavior through gut and brain control. They successfully delivered optogenetic stimulation to the ventral tegmental area (VTA) of the brain, inducing dopamine release and encouraging mice to seek out specific chambers associated with dopamine rewards. By releasing sucrose through the gut fibers, they observed a similar reward-seeking behavior triggered by dopamine activation in the brain. Additionally, by optogenetically stimulating nerve endings in the gut connected to the vagus nerve, which regulates digestion and bodily functions, the researchers achieved place preference behavior without directly affecting the brain.

Furthermore, the team explored the control of feeding behaviors by optogenetically stimulating cells that produce specific hormones related to satiety. When cells producing cholecystokinin or PYY were activated, the animals’ appetites were suppressed, even after fasting or consuming rich foods.

Moving forward, the researchers plan to utilize this fiber interface to investigate neurological conditions believed to be associated with the gut-brain connection. By exploring the potential connection between the gut and the brain, they aim to develop less invasive methods of managing conditions such as autism and anxiety, manipulating peripheral circuits without directly affecting the brain.

By Impact Lab