MIT probe modulates neural circuits in gut and brain

26 Jun 2023

Device integrates LEDs, electrodes, thermal sensors and microfluidic channels.

Studying the complex operations of neural circuits connecting the brain and the major organs such as the digestive tract requires inventive optical devices able to operate in situ during normal behavior.

In particular, the signals that pass between the brain and the nervous system of the gut, called the enteric nervous system, are known to influence hunger and satiety via both neuronal communication and hormone release, but understanding the details will need suitable implanted optical instruments.

A project at MIT has now developed a new technology for probing these connections, and designed a device intended to be both implantable and capable of remaining operational for extended periods.

Described in Nature Biotechnology, the device is based on meters-long continuous fibers that can support integrated light sources, electrodes, thermal sensors and microfluidic channels in a miniature footprint.

MIT has previously investigated methods to improve the stimulation and detection of fluorescence in living tissues, for example by modulating the frequency of the fluorescent light emitted by the sensor so that it can be more easily distinguished from tissue autofluorescence.

The new device was designed to address the shortage of suitable implantable bio-integrated multifunctional devices. There remains a need for monolithic and scalable fabrication approaches that do not compromise the design flexibility, multimodality, sophistication and biocompatibility of bioelectronic interfaces, according to the project team.

"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," said Atharva Sahasrabudhe from MIT. "So we decided to make it."

Neurological conditions with a gut-brain connection

The team's design involved multifunctional bioelectronic interfaces based on polymer fibers embedded with solid-state components, manufactured through thermal drawing processes. Initially manufactured in long lengths, the fibers can then be sectioned into thousands of individual small probes for animal studies.

Such fibers can host multiple independently addressable microLED chips for optogenetics stimulation, and MIT successfully mounted blue and green light sources at 470 and 527 nanometers along the fiber surface. The device architecture allows thermal sensors and microfluidic channels for drug delivery to be incorporated as well.

The assembled device can be controlled wirelessly using a bespoke external control circuit christened NeuroStack, that can be temporarily affixed to the animal during an experiment.

"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," said Sahasrabudhe. "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."

In trials researchers used the probe and its microLEDs to optogenetically sense and modulate neural activity in the brain and the gut of freely behaving animals, finding that risk-reward behavior could be induced by stimulating the gut rather than the brain. This suggests that the device could be valuable in the study of neurological conditions believed to have a gut-brain connection.

"We can now begin asking if those are coincidences, or if there is a connection between the gut and the brain," said MIT's Polina Anikeeva. "Here is an opportunity for us 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."