Hungarian researchers have developed virtual reality glasses for mice.

The BrainVisionCenter Research Institute and Competence Center (BVC), in collaboration with the HUN-REN Institute of Experimental Medicine, has developed a unique virtual reality (VR) headset optimized for mice. This innovation opens new horizons in the study of brain function and the development of vision-restoring brain-computer interfaces. The device, named Moculus, is the first to enable the realistic simulation of natural vision in experimental animals. While previously it took experimental animals 5–9 days to learn to differentiate between two images, with the new device, this learning process can now be 100 times faster. This means that studying the mechanisms of vision is now possible within an hour.

Their newly developed virtual reality system, combined with rapid 3D imaging, has enabled rodents to perform fast visual learning tasks in as little as one day. Moculus provides a more realistic virtual presence for mice in the VR world through a lifelike, stereoscopic display, significantly accelerating the learning process.

Over the past 20–30 years, neuroscientists, pharmaceutical companies, and corporations have developed numerous virtual reality tools to study the vision of experimental animals. However, these tools all relied on two-dimensional projections to represent virtual spaces, assuming that experimental animals, like humans, could understand and reconstruct the surrounding 3D reality from two-dimensional projections, such as the flat image of a television screen. Recent research, however, has revealed that this assumption is incorrect. For rodents, two-dimensional projections do not provide a realistic experience, which distorts the results.

This was illustrated with a simple yet convincing example: mice ran across a virtual abyss displayed on traditional VR screens without hesitation. In contrast, they almost immediately stopped and even retreated backward when the abyss was presented using the newly developed Moculus system, as they perceived it to be realistic.

In other words, the Moculus project demonstrated that mice can only perceive the world in three dimensions if the virtual reality is precisely calculated and projected in a way tailored to their vision, replicating how they see reality. This is because, unlike humans, mice lack sufficient capacity for abstract visual thinking.

The Moculus VR system includes a specialized treadmill that records and transmits data on the mouse’s movements, two screens, and an optical imaging system designed to match them. This system provides a field of view wider than 180 degrees, which is essential for mice, allowing them to interact naturally with the virtual environment. Meanwhile, researchers can use two-photon microscopy to precisely map the brain activity patterns of the mice. Mapping these patterns offers insights into how animals learn and the neural mechanisms that regulate decision-making. These studies not only enhance our understanding of fundamental brain functions but also contribute to the development of therapeutic solutions for neurological disorders, such as vision impairments.

The essence of learning lies in the fact that these rich neuronal representations compete with one another. During learning, a kind of “competitive process” takes place in the brain among spatiotemporal neuronal representations. The goal of this competition is to encode behaviorally relevant information, such as rewards or punishments. Researchers have demonstrated that feedback derived from rewards and punishments serves as the critical information that continuously teaches and reprograms the functioning of the entire neural network at the cellular level. This process ultimately determines the “winning” representation, which dominates the encoding, while the coding of other previously competing information decreases and returns to baseline activity.

**Moculus Measurements:** a) The experimental setup: the virtual reality glasses, Moculus, combined with two-photon microscopy measurements while the mouse performs a discrimination learning task. b) Calcium signals measured in the visual cortex under control and aversive stimuli conditions.

According to the current state of the literature, neuronal activity in the visual cortex increases by only about 10% as a result of learning. However, the most recent studies report even more surprising findings, including cases of 0% change in activity or even decreases in activity. It is important to note that in these earlier studies, training mice took at least 5–9 days, providing ample time for various processes to reorganize brain activity patterns.

The ultra-fast learning capability provided by Moculus has, for the first time, enabled the capture of a snapshot of brain activity before reorganization processes have begun. The results revealed that the functioning of vision differs significantly from previously established textbook data. The brain can temporarily activate nearly all neurons in the visual cortex to perform visual tasks, thereby maximizing its computational capacity to ensure the richest possible representation of the specific visual components.

The study of mice using VR headsets opens new possibilities in neurobiological research and can contribute to a more comprehensive understanding of the human brain’s functioning. The project’s most significant achievement is that the new tool generates spatiotemporal brain activity patterns that encode specific visual elements of the environment with unparalleled precision and depth. This capability allows vision restoration devices based on 3D acousto-optical microscopy to reactivate neuronal activity more accurately than ever before, enabling the creation of much more precise artificial vision.

**Competing Networks**: a) The effects of learning can be detected as early as 30 minutes into the session, both in movement speed and calcium signals. However, the shift in calcium signals is more pronounced than the speed response, demonstrating that these are genuine anticipatory signals rather than mere projections of speed changes onto calcium signals. b) At the beginning of learning, speed increases in both aversive and control zones, but after prolonged training, the mouse recognizes the conditioning signal, and the phenomenon persists only in the aversive zone. c) A similar pattern is observed in calcium signals.

The mouse VR system has generated significant interest in the market for neuroscience research tools, as no similar device is currently available. One of its major advantages is its compact, modular design, which allows it to be easily integrated with various electrophysiological or imaging equipment, such as two-photon microscopes.

The project is the result of a collaboration between the BrainVisionCenter, founded in 2021 by Botond Roska, Balázs Rózsa (Director), and the Ministry of Innovation and Technology, and the HUN-REN Institute of Experimental Medicine. The research was supported by grants ERC-682426 (VISIONby3DSTIM), GINOP-2016, NKP-2017, VKE-2018, GINOP-2021-00061, PM/20453-15/2020, KFI-2018-097, AMPLITUDE, GYORSÍTÓSÁV-2021-04, GINOP_PLUSZ-00143, GYORSÍTÓSÁV-2022-064, NL-2022-012, KK-2022-05, ED-2021-00190, ED-2022-00208, and Gergely Szalay’s NKFIH/143650 research fellowship.

Gergely Dobos, Balázs Rózsa, and Gergely Szalay are the inventors of the PCT/HU2020/050029 patent.

Publication: Moculus: an immersive virtual reality system for mice incorporating stereo vision

DOI: 10.1038/s41592-024-02554-6