Researchers at Northwestern University have developed new virtual reality (VR) goggles for mice. The device provides a more immersive experience for mice living in a laboratory environment, allowing researchers for the first time to study responses to overhead threats. By more realistically simulating natural environments, researchers can more accurately and precisely study the neural circuits underlying behavior.
An advanced leap forward in virtual reality glasses
The new goggles are a leap forward from current state-of-the-art systems that simply surround mice with computers or projection screens. In the current system, mice can still see the laboratory environment peeking out from behind the screen, and the flat nature of the screen cannot convey three-dimensional (3D) depth. Another drawback was that the researchers couldn't easily mount the screen above the mice's heads to simulate overhead threats, such as looming prey.
New VR goggles solve all these problems. And, as VR technology becomes more commonplace, the goggles could also help researchers gain insights into how the human brain adapts and responds to repeated VR experiences—an area that is currently poorly understood.
The research results were published in the journal Neuron on December 8. This is the first time researchers have used a VR system to simulate high-altitude threats.
"We've been using VR systems to study mice for the past 15 years," said Daniel Dombeck of Northwestern University, the study's senior author. "To date, labs have used large computers or projection screens to surround the animals. For humans, it's like watching TV in your living room. You You can still see the couch and the wall. The cues around you are telling you that you're not in the scene. Now think about wearing VR goggles, like the Oculus Rift, which takes up your entire field of view, and each eye sees a different scene, which is what mice have been missing."
Dombeck is professor of neurobiology in Northwestern University's Weinberg College of Arts and Sciences. His laboratory is a leader in developing VR-based systems and high-resolution laser imaging systems for animal research.
The value of virtual reality
While researchers can observe animals in nature, it is difficult to image real-time brain activity patterns as animals come into contact with the real world. To overcome this problem, researchers integrated VR technology into the laboratory environment. In these experimental settings, animals use a treadmill to navigate a scene, such as a virtual maze, projected onto a surrounding screen.
Neurobiologists can use tools to see and map the brain of a mouse as it travels through virtual space, rather than having it run through a natural environment or a physical maze. Ultimately, this helps researchers understand general principles of how activated neural circuits encode information in a variety of behaviors.
"VR basically recreates a real environment," Dombeck said. "We had a lot of success with this VR system, but the animals may not be as immersed in it as they would be in a real environment. Getting mice to pay attention to the screen and ignore the lab surrounding them requires a lot of training."
With recent advances in hardware miniaturization, Dombeck and his team wondered if they could develop VR glasses that more faithfully reproduce real-life environments. They used custom-designed lenses and tiny organic light-emitting diode (OLED) displays to create tiny goggles.
The system, called Microrodent Stereoscopic Illumination VR (iMRSIV), consists of two lenses and two screens - one on each side of the head, to provide 3D visual illumination for each eye. This provides a 180-degree field of view for each eye, allowing the mouse to be fully immersed and excluded from its surroundings.
Unlike human VR goggles, the iMRSIV (pronounced "immersive") system doesn't wrap around the mouse's head. Instead, the goggles were attached to the experimental apparatus and fit snugly against the mouse's face. Since the mice were running in place on the treadmill, the goggles still covered the mouse's field of vision.
"We designed and built a custom holder for the goggles," said study co-first author John Issa, a postdoc in Dombeck's lab. "The entire optical display - screen and lens - surrounds the subject at all times."
By mapping the brains of mice, Dombeck and his team found that the brains of mice wearing goggles activated in a manner very similar to that of freely moving animals. And, in side-by-side comparisons, the researchers noticed that mice wearing the goggles integrated into the scene faster than mice using a traditional VR system.
"We did the same training paradigm as in the past, but the mice wearing the goggles learned faster," Dombeck said. "After the first training session, they were able to complete the task. They knew where to run and looked for rewards in the right places. We thought they might actually not need that much training because they could engage with the environment in a more natural way."
High-altitude threats simulated for the first time
Next, the researchers used the eyepiece to simulate a high-altitude threat—something not possible with current systems. Because the imaging technology hardware is already mounted above the mouse, the computer screen has nowhere to mount it. However, the sky above mice is an area where animals often seek out important information, sometimes of life or death.
"The top of the mouse's visual field is very sensitive and can detect predators, such as birds, coming from above," said co-first author Dom Pinke, a research specialist in Dombeck's lab. "It's not a learned behavior, it's an imprinted behavior. It's already established in the mouse brain."
To create an imminent threat, the researchers projected an expanding dark disk at the top of the goggles—the top of the mice's field of vision. In experiments, mice either ran faster or froze after noticing the disk. Both behaviors are common responses to overhead threats. Researchers were able to record neural activity and study these responses in detail.
"In the future, we would like to study situations where mice are not prey but predators," Issa said. "For example, we could look at the brain activity of mice when they chase flies. This activity involves a lot of depth perception and distance estimation. These are things we can start to capture."
In addition to opening the door to more research, Dombeck hopes the goggles will open doors for new researchers. Because the goggles are relatively inexpensive and require little lab setup, he believes the goggles could make neurobiological research more accessible.
"Traditional VR systems are quite complex," Dombeck said. "They are expensive and bulky. They require a lab with a lot of space. Also, if it takes a long time to train mice to complete a task, it limits the number of experiments. We are still improving, but our goggles are small, relatively cheap, and very user-friendly. This could lead to greater use of VR technology in other labs."
Reference: "Full-field virtual reality goggles for mice" published in Neuron by Domonkos Pinke, John B. Issa, Gabriel A. Dara, Gergely Dobos, and Daniel A. Dombeck on December 8, 2023.
DOI:10.1016/j.neuron.2023.11.019
Compiled source: ScitechDaily