ETHZ-led group shows that nervous system directly influences immune system

29 Sep 2020

Optogenetics researchers in Switzerland and US have optically stimulated nerve fibers in living mice.

Researchers at ETH Zurich – in collaboration with colleagues from EPFL in Lausanne, both in Switzerland, and Harvard Medical School, Cambridge, MA – have developed a laser-based system that allows them to optically stimulate individual nerve fibers in living mice.

Through this process, they have demonstrated that the nervous system has a direct influence on the immune system.

Over the past ten years, a new method has literally shed more light on the brain: optogenetics allows scientists to dstimulate genetically-modified nerve cells and investigate their functioning within the complex network inside the skull. This technique represents a revolution in neuroscience, say the Swiss-US team, but to date, it could only be applied to study the central nervous system, and not the peripheral nervous system.

A team of electrical engineers led by Qiuting Huang, a professor at the Institute for Integrated Systems at ETH Zurich, have developed a system that connects implantable LEDs with a tiny device on the subject’s head which can be controlled from a tablet via Bluetooth. They have stimulated, with great precision, nerve fibers in the bodies of freely-moving mice, as the scientists report in Nature Biotechnology.

“Our goal was to develop an integrated platform as small as possible. Together, the chip, the battery and the antenna for wireless signal transmission weigh less than one gram – and occupy less than one cubic centimetre,” explained Huang.

While the chip technology enables high integration density of electronic circuits, there are limits to miniaturization, particularly with batteries; the smaller the volume, the greater the energy density. This, in turn, increases the risk that batteries might ignite.

The team originally intended to develop this platform for a project to measure oxygen saturation and blood pressure, but right from the outset of the design phase, they endeavored to ensure the widest possible application for the chip.

“Because our system is programmable, we were able to take the electronic circuits that we had been intending to use to measure oxygen saturation in blood and re-purpose them to control the implanted light emitting diodes,” said contributing scientist Philipp Schönle.

Made for each other

The group has been collaborating with Stéphanie Lacour’s group at EPFL for five years. “Our sophisticated electronics and their soft bioelectronic sensors were made for each other,” said Huang. Advances in material sciences and electronics build on each other – and interconnect with each other. “Together, we have developed an approach that allows us to stimulate a specific nerve fiber in the body of the mouse at precise points in time,” added Schönle.

At Harvard Medical School, a research group led by Clifford Woolf wrapped the implants around the sciatic nerve. Without damaging the nerve, over several days, they managed to repeatedly use blue light flashes to activate specific nerve cells – known as the “nociceptors”, which specialize in the transmission of pain signals.

To their surprise, the researchers discovered that repeated optical stimulation of these nociceptors produced a slight reddening in one of the mouse’s hind paws, a clear sign of inflammation.

Scientists had previously assumed that pain and inflammation were two different processes that arose independently. “But now we have been able to prove conclusively that the neurons responsible for pain sensations can also generate an inflammatory immune response,” said Woolf. As the researchers explain in the Nature Biotechnology article, these results may potentially point the way to new approaches in such areas as the treatment of chronic pain, or persistent inflammation.

Huang believes that electrical engineering will play an increasingly important role in human health in the future. He highlights the term “electroceuticals” – a combination of electronics and pharmaceuticals – which is already being discussed among experts.