An ultra-thin, flexible probe that can record and stimulate neurons in the brains of mice

Researchers have designed an ultra-thin, flexible and minimally invasive neural probe that is capable of not only recording neural activity, but also stimulating specific sets of neurons using light.

Described in a new study in Nature Communications, the probe is about one-fifth the width of a human hair and would be ideal for studying small and moveable areas of the nervous system, such as the spinal cord or the peripheral nerves (the nerves outside the brain and spinal cord that relay information between the brain and the rest of the body). 

“This is where you’d need a really small, flexible probe that can fit in between vertebrae to interface with neurons and can bend as the spinal cord moves,” says co-senior author Axel Nimmerjahn, associate professor in the Waitt Advanced Biophotonics Centre at the Salk Institute for Biological Studies, US.

The neural probe can also be implanted for longer periods because it’s more compatible with biological tissue and less prone to triggering an immune response.

“For chronic neural interfacing, you want a probe that’s stealthy – something that the body doesn’t even know is there but can still communicate with neurons,” says study co-senior author Donald Sirbuly, professor of nanoengineering at the Jacobs School of Engineering at the University of California San Diego, US.

What sets this probe apart from other existing ultra-thin, flexible probes is that it consists of both an electrical channel and an optical channel that can record the electrical activity of neurons and stimulate specific sets of neurons using light.

“Having this dual modality – electrical recording and optical stimulation – in such a small footprint is a unique combination,” explains Sirbuly.

New neural probe a feat of clever engineering

The electrical channel contains an ultra-thin polymer electrode (that can conduct electricity), whereas the optical channel contains an ultra-thin optical fibre that transmits light. Putting the two together in the same neural probe took some very clever engineering.

The channels had to be insulated to stop them from interfering with each other, while fitting into a tiny probe with a diameter of just eight to 14 micrometres. The researchers also had to make sure the probe was flexible, durable, biocompatible and able to perform just as well as existing state-of-the-art neural probes.

Once fabricated, the neural probes were implanted into the brains of live mice for up to one month, during which they caused hardly any inflammation of the brain tissue.

The probes were able to record electrical activity from neurons with high sensitivity and could also be used to stimulate neurons in the mice’s cortex to move their whiskers.

“Currently, we know relatively little about how the spinal cord works, how it processes information, and how its neural activity might be disrupted or impaired in certain disease conditions,” says Nimmerjahn.

“It has been a technical challenge to record from this dynamic and tiny structure, and we think that our probes and future probe arrays have the unique potential to help us study the spinal cord – not just understand it on a fundamental level, but also have the ability to modulate its activity.”

And because virtually any microfibre length can be achieved, the fabrication process could be used to develop neural probes that can reach even deeper brain regions. With the probe’s stiffness decreasing with length, however, changes to the design – such as a dissolvable sugar coating or rigid polymer layers – may be needed to prevent bending.