In dark rooms, surrounded by illuminated screens, figures scuttle, duck, and navigate through twisting corridors and mazes. This isn’t the elaborate setup of a teen gaming lair; rather, it’s a high-end virtual reality system built for neuroscience’s favorite mammals: rodents.
Tour a neuroscience lab fifteen years ago and you might see rats or mice swimming in circular water tanks or exploring T-shaped physical mazes as part of research on memory, spatial navigation and vision. By studying how rodents perform on these tasks, researchers try to understand similar brain functions in humans, which in turn could help find treatments for conditions like Alzheimer’s disease, ADHD and autism. Today though, a growing number of labs around the world are turning to virtual reality as a new experimental approach to answer the same questions about the brain.
Inside a Virtual Reality Lab
Have you ever been to a show at a planetarium, sitting inside a dome viewing images of the night sky? Aman Saleem, Ph.D., a Professor of Systems Neuroscience and the Sir Henry Dale Fellow at University College London says VR setups in neuroscience labs are “like planetariums for mice” – in which one mouse can move around and even control the projected images. By interacting with a simulated environment projected onto a physical dome, a rodent receives visual sensory inputs. These inputs activate sensory neural circuits in the brain, which in turn activate other circuits. Researchers then study the resulting brain activity through techniques like electrical recordings and fluorescence microscopy.
Depending on what brain regions are being studied, labs create different VR environments for their rodents. Saleem, who studies how vision is used to navigate space, places mice in planetarium domes on free-moving treadmills. These mice see down a long, black-and-white VR corridor and their movements control the scene.
“If the mouse runs forward, it goes forward in the corridor, Saleem explains. “If it walks backwards, it’s going to go backwards in the corridor – just like in the real world.”
The mouse’s head is held fixed so that Saleem can view real-time electroencephalogram (EEG) recordings, which measure electrical activity in the brain. From electrodes implanted in its primary visual cortex and hippocampus, images are received from the eyes to create a “map” of the hallway for navigation and movement. Saleem hopes this will help him understand how vision and navigation are linked.
Mayank Mehta, Ph.D., is the director of the Keck Center for Neurophysics and Professor of Physics and Astronomy, Neurology, and Electrical and Computer Engineering at the University of California, Los Angeles. The simulated environments found in his lab reflect his interests in memory and learning. Mehta uses VR to investigate questions such as how does the healthy brain learn? How does the brain abstract out concepts and remember things? And what goes wrong in conditions like Alzheimer’s and ADHD? To study this, Mehta invokes abstract idea creation in rats, through assigning them one of the most complex tasks they can do.
“We ask the rat to solve a complicated maze in VR,” Mehta explains.
Rats are placed on a moving sphere inside a planetarium dome and, given a little incentive, they learn quickly to perform tasks like navigating to spotlights.
“They have to figure out, what is the shortcut? Where is the reward? What is the bad place? What is the good place? When they do the right thing, they get a drop of sugar water, which they love,” Mehta says. “Surprisingly, neurons in the hippocampus show new signals, never seen before in rodents, but very similar to those in the human brain. This means that rodents in VR illuminate human brain function or pathology. A great tool for pharmaceutical companies!”
It’s important to Mehta that his rats learn in a stress-free environment so that his findings reflect the activity of a normal, healthy brain. Instead of restraining his rats’ heads, he fits them with “tuxedo vests.”
“They happily walk around all over the lab in their tuxedos,” Mehta says. “It mimics how their mothers pick them up from the back. When they don’t want it, they can still slip out of the vest. And they take naps in VR. That’s the gold standard, where they feel comfortable enough to fall asleep.”
And his setup minimizes stress too.
“When the rats look somewhere, they can see their own paws. They can see their whiskers. They can see their shadows. There is no dizziness,” Mehta explains.
Pros and Cons
Neuroscientists who use VR say the control it provides in experiments is invaluable. In traditional physical maze tasks, rodents move freely and respond to many sensory stimuli that are difficult to track. In VR though, “we can easily manipulate the visual environment and more easily understand how we go from vision to memory,” Saleem says.
VR is also compatible with experimental techniques that can study the brain on a finer level. VR environments restrict the movement area of animals and sometimes also restrain their heads, allowing researchers to use instruments like intracellular electrodes one micron in diameter.
“We can look at the transformation across different brain areas and track how information is processed,” Saleem says. “So we can do research that is otherwise not possible.”
However, rodent behavior in VR may not track with behavior in real life. Like humans who know a racing game at the arcade isn’t real because it lacks the sensory data of real life, rats in VR mazes are aware that their experience doesn’t sync with smell, feel, and sound. Research from the Mehta lab has shown that the hippocampal neurons of rodents, which are involved in space perception, fire differently when the animals are in VR simulations as opposed to similar environments in the real world.
Whether the “virtual” aspect of virtual reality is a detriment depends on the research question being asked. For his research on learning and memory, Mehta believes that VR actually improves the predictive power of animal models.
“Rats strongly rely on touch with their whiskers and smell, but when humans are learning and using memory, we primarily use our eyes and ears,” Mehta explains. “In VR, rats are removed of their ability to rely on their touch and olfaction, so they are a better approximation of humans.”
To understand other questions about the brain, VR may not be a good fit. For instance, Mehta notes that diseases related to the motor cortex, such as Parkinson’s and amyotrophic lateral sclerosis (ALS), require greater testing in real-world conditions.
Ultimately, Saleem says, “any scientific method has its limitations, and VR is the same. The important thing is to not overinterpret the data and to be aware that it is collected from a controlled virtual environment. This is the only way that we can actually do science – by cutting out the thousand different influences on the brain that we have in the real world and starting from a simplified view.”
The Future of VR
Drawing parallels between lab VR and the reality-bending classic movie The Matrix? You’re not alone. The high-tech implications of rodent VR aren’t lost on Saleem, a self-described “enthusiast about science fiction.” He’s embraced his status as “master architect” of the electrophysiology rigs in his lab, which contain microelectrode and amplifier equipment for recording the electrical activity of neurons. The rigs are named after The Matrix characters Neo, Trinity, and Morpheus. Another of Saleem’s lab rooms was christened the Holodeck, from Star Trek’s simulation devices of the same name. Saleem notes that, while comparisons to science fiction are “a little extreme, given that they are completely artificial, our VR aims to immerse animals in a similar way.”
And Saleem and Mehta promise that VR in the lab is much more positive than its counterparts in dystopian sci-fi.
“Our animals are happy and comfortable and ultimately we hope that findings from VR will help humans,” Mehta says. “In fact, our recent findings show that VR can boost both beneficial brain rhythms and neuroplasticity, with possible applications for learning and memory prostheses. I’m really excited for future applications that will arise as we develop more authentic reality systems.”
- A growing number of labs around the world are turning to virtual reality as a new experimental approach to answer key questions about the brain. This includes animal-based VR studies.
- Depending on what brain regions are being studied, labs create different VR environments for their rodents.
- For research on learning and memory, some scientists believe VR improves the predictive power of animal models.
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D’Isa, R., Comi, G. & Leocani, L. Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze. Sci Rep 11, 21177 (2021). https://doi-org.stanford.idm.oclc.org/10.1038/s41598-021-00402-7
Aghajan, Z., Acharya, L., Moore, J. et al. Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality. Nat Neurosci 18, 121–128 (2015). https://doi.org/10.1038/nn.3884
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Phoebe Hall is the assistant director of biomedical communications at Brown University. She is the staff writer for Medicine@Brown magazine, covering health and science research and clinical work by faculty, alumni, and students. She earned her bachelor’s in ecology and evolutionary biology at UConn and her master’s from the Medill School of Journalism at Northwestern. Before coming to Brown in 2013, Phoebe worked as a newspaper reporter and editor, the managing editor of the alumni magazine of Connecticut College, an environmental lab technician, and a zookeeper. She’s passionate about clear, balanced, and accurate science journalism, and the value of mentorship. She lives with her husband and their cat on Narragansett Bay in Rhode Island, where she can ride her bike to work and the beach.
Mayank Mehta, Ph.D., is Director of the Keck Center for Neurophysics and Professor of Physics and Astronomy, Neurology, and Electrical and Computer Engineering at University of California, Los Angeles. His lab’s research focuses on fundamental questions in neurophysics around the general themes of learning and memory, space-time perception and sleep, with the goals of greater understanding neural circuit dynamics and elucidating novel ways to treat learning and memory disorders.
Aman Saleem, Ph.D., is Professor of Systems Neuroscience and Sir Henry Dale Fellow at University College London. His lab uses computational and experimental approaches to understand how the brain uses visual images observed by the eyes for natural functions such as navigation.