Stimulating or inhibiting particular neurons in an animal and observing the effects is the basis of countless neuroscience experiments. To achieve such control, researchers have two key methods at their disposal: pharmacology and optogenetics.
But methods for targeting drugs or light to specific neurons may interfere with the behavior or neuronal activity under observation. Animals generally need to be handled for drug injections, for example, while light stimulation often requires illuminating an animal’s skin or tethering the creature to a fiber optic cable.
To minimize disturbance to animals during experiments, engineers are developing small wireless devices containing light-emitting diodes (LEDs) or microfluidic channels (for drug delivery) that can be surgically implanted. But, as yet, such devices are inflexible, bulky, and only suitable for brain stimulation, for which they can be anchored to the skull, says neuroscientist Robert Gereau of Washington University in St. Louis. To stimulate nerves in the rest of the body, he adds, you need a device that “moves with the tissue. It can’t be rigid.”
To that end, Gereau and colleagues have built a device that consists of a tiny base unit (5 mm in diameter) and a long, soft, flexible cuff (approximately 20 mm x 2 mm). The base unit houses microfluidic reservoirs and pumps as well as electronics that control the pumps, illuminate a microscale LED sitting at the far end of the cuff, and collect power transmitted wirelessly from outside the animal, eliminating the need for a battery. Running the length of the cuff are microfluidic channels through which the reservoir fluids are pumped, and a wire connects the base to the LED. The base is sutured onto an animal’s back, with the cuff inserted into the body and attached to a nerve bundle of interest.
In proof-of-principle experiments, the team hooked up the device to the sciatic nerve in mice’s hind legs and showed that in animals engineered to have light-sensitive pain neurons, switching on the LED induced discomfort. Conversely, pumping an anesthetic to the sciatic nerve of wild-type mice increased the animals’ tolerance to pain.
The researchers “take two very distinct technologies . . . and combine them into one single device,” says pain researcher Gregory Corder of the University of Pennsylvania, who was not involved in the research. It can be used “in an awake, behaving animal without an experimenter being present in the room,” he adds. “It’s extremely impressive.”
Y. Zhang et al., “Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves,” Sci Adv, 5:eaaw5296, 2019.
|Peripheral nerve stimulation technique||Ease||Potential for behavioral confounding||Temporal precision of nerve activation||Spatial precision of nerve activation|
|Existing optogenetic and pharmacological methods||High. Products and protocols for light stimulation and injections are established and readily available.|
High. Researcher interaction is often required, which may cause fear.
|High for light stimulation; low for drug injections||Low|
|Implanted optofluidic device||Low. Surgery is required to implant the device, which is not yet readily available.||Unlikely. The device is remotely controlled.||High for both light- and drug-induced activations||High. The device is directly attached to nerve bundle.|