Wi-fi optogenetic units sync neurons amongst mice | Spectrum
Tiny device: A new optogenetic device can be implanted completely under the skin of a mouse and controlled wirelessly so that the animals can move freely during the experiments.
Courtesy of Yiyuan Yang
Two new wireless devices can synchronize the neural activity of multiple mice at the same time, allowing researchers to study how brain-to-brain synchronization underlies social behavior.
The devices, described in Nature Neuroscience in May, use optogenetics, a technique that uses pulses of light to activate or silence neurons designed to express light-sensitive proteins called opsins. The same technique was used to study the role of the hormone oxytocin in social behavior relevant to autism.
Traditional optogenetic devices rely on a stream of cables that can limit both the speed and distance of animals’ movements, making it difficult to study the relationship between neural activity and social behavior.
Researchers have developed wireless, battery-powered optogenetic devices that can be attached to an animal’s head, but these devices are often bulky and distracting. “Mice tend to gnaw at the head-mounted devices, so we wanted fully subdermal implants,” said John Rogers, director of the Querrey Simpson Institute for Bioelectronics at Northwestern University in Evanston, Illinois.
Rogers and his colleagues have developed a thin device about 1.2 millimeters thick that they can attach under the skin on the head of a mouse. It has two micro-LED lights attached to the ends of sharp probes that can be injected into the skull and controlled independently.
The team has also developed a larger, more powerful device that can be mounted on an animal’s back. It has four micro LEDs on the tips of metal coils that extend up the neck and into the skull. The larger device can stretch and flex to accommodate the wide range of motion of a mouse.
Both devices are powered wirelessly and can be controlled in real time from a nearby computer, allowing researchers to modulate the optical intensity, pulse duration and frequency of each light on up to 256 animals simultaneously without interfering with their movement.
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Social synchronization: Synchronized stimulation of the medial prefrontal cortex increases social behavior in mice. Courtesy of Yiyuan Yang
In a series of experiments, the researchers implanted the rear-mounted devices in mice and then monitored their movements as they explored a rectangular cage. The wireless devices did not reduce the activity or speed of the animals compared to mice without the device, while mice with a wired optogenetic device were sluggish and less moving.
The devices remained functional in the mice for more than nine weeks without damaging the brain tissue, the study shows. And similar implants from the team remained functional for longer without causing any significant damage, says Rogers. “We’ve had animals that have worn these devices essentially their entire lives, 2 years or more until they die of natural causes.”
The team then tested the devices on mice engineered to express an opsin protein in dopamine neurons in the ventral tegmental area, a region of the brain involved in reward processing and social behavior. They placed a mouse with the optogenetic device in a cage with a toy and another mouse of the same sex. Stimulating the dopamine neurons almost doubled the time mice spent interacting with the other animal, but didn’t change the amount spent near the toy, suggesting that the device was successfully targeting the social reward circuitry .
According to previous research, brain activity between people is synchronized during social interactions. This synchronicity between the brains can strengthen social bonding and can be compromised in people with autism, although research on the topic has produced mixed results.
Rogers’ team investigated whether synchronized stimulation of the medial prefrontal cortex, a region of the brain involved in social behavior and cognition, would increase social bonding in mice. They constructed three mice to express the opsin protein in pyramidal neurons of the medial prefrontal cortex and then implanted an optogenetic device in each animal.
They stimulated two of the animals at the same frequency and gave the third animal a unique rhythm. The “paired” mice showed more social behavior – they approached their partner and sniffed him – while the third animal showed typical, non-social behavior.
The devices can be used to conduct even larger, population-based behavioral studies on hundreds of animals simultaneously over long periods of time, says Rogers. And they could help provide insights into the mechanisms underlying atypical social behaviors, say Rogers and his colleagues.