Mice Play Quake II in Virtual Space

A marine named Bitterman runs through the virtual landscape of Quake II carrying a blaster, a railgun, a rocket launcher, or a shotgun and shooting anyone in his way. Quake II –- one of the all-time popular first person shooter video games –- involves an assault on an alien planet, Stroggos, mounted in retaliation for Strogg attacks on Earth. You must shoot the aliens before they shoot you.

Here’s a video of the classic commercial advertising the release of Quake II on Nintendo and PlayStation gaming platforms:

Molecular biologist David Tank at Princeton University and his colleagues have created a special hacked version of Quake II using its underlying physics engine. But this game is for mice, not people. And don’t expect to see helmeted mice in camouflage fatigues packing heat in virtual space any time soon.

Tank’s special custom version of Quake II is actually a novel approach to the study of how the brain’s hippocampus creates maps of its surroundings. “The mouse is playing a video game," says Tank. The harnessed mouse walks atop a floating styrofoam ball –- essentially a treadmill –- and navigates through virtual corridors:

The mouse’s ball is kept aloft by a jet of air. It is surrounded by sensors taken from optical computer mice (like the ones you use to control your computer’s cursor) that read the ball’s movement as the mouse runs through the corridors. Wired reports that rather than “earning points or power-ups,” the mice were rewarded with sips of water from a head-side nozzle.

Dr. Tank’s research involves persistent neural activity in experiments that use advanced electro-physiological, imaging, and genetic techniques. His innovative gaming platform for rodents is a clever way of overcoming the problem of tracking individual neurons in moving animals. Along with Christopher Harvey, Forrest Collman, and Daniel Dombeck, Dr. Tank co-authored a paper on the Quake II experiment, recently published in Nature, titled “Intracellular dynamics of hippocampal place cells during virtual navigation.”

With mice running around the virtual landscapes of Quake II, researchers can record the response of individual neurons.

Using place cells, the researchers made the first direct measurements of the cellular activity associated with spatial navigation. Place cells are neurons in the hippocampus that exhibit a high rate of firing whenever an animal is in a specific location in an environment. Place cell neurons are distinct from other neurons with spatial firing properties. These other neurons include grid cells, border cells, head direction cells, and spatial view cells.

In mice, spatial navigation involves at least four different cell types located in the hippocampus and surrounding regions. Place cells increase their activity when the animal is near a place field. Grid cells, in contrast, fire periodically as the animal traverses a space. Head direction cells, as their name implies, fire when the animal is facing a particular direction. Only recently identified, border encode the animal’s distance from the borders within its environment.

David Tank - Photo credit: molbio.princeton.eduIn the virtual environment, Dr. Tank and colleagues found that place cells behaved as expected. All cells generated short, regular bursts of nervous impulses, separated by intervals of about one tenth of a second in recordings taken during the experiment. This produced a low level of background theta oscillation with a frequency of 6-10 cycles-per-second, which is characteristic of the hippocampus. The researchers found that individual place cells appeared to be modulated by location. As the mouse entered a given place field, the corresponding place cell increased its firing rate.

The hippocampus is one of many brain structures that show a characteristic oscillation –- theta rhythm -– in an EEG recording. The oscillation has been observed in all mammalian species tested. In both rats and humans, it is associated with real or virtual movement through space. Now, with mice running around the virtual landscapes of Quake II, researchers can record the response of individual neurons. The custom Quake II virtual environment can also be used in combination with other experimental techniques such as two-photon laser scanning microscopy. “One of the major research areas of neuroscience is the development of techniques to study the brain at cellular resolution,” says Tank. “The information of the nervous system is contained in the activity of individual neurons.”

Such precision may be decisive in determining how cells in the mammalian cortex encode location –- our “sense of direction” –- and ultimately how we find our way around, whether in a virtual world like Stroggos or on Earth.

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