It is the world's first device to image brain activity at the cellular scale in freely moving mice.

Roughly the size of a dime and weighing only 1.1 grams, the miniaturized microscope developed by Mark Schnitzer, assistant professor of biology and of applied physics, captured the first images of firing neurons and circulating red blood cells in the brains of active mice—a feat that has never before been accomplished.

Described in a paper published Oct. 5 in the online edition of Nature Methods, the microscope can collect images at up to 3-micron resolution and speeds of 100 frames per second, allowing scientists to perform real-time observations of the underlying cellular processes in the brain that are responsible for behavior in mice.

Previously, experiments correlating behavior and brain activity in mice were not possible due to the bulky size and mass of microscopes, which would weigh down the animals.

Incorporating super-lightweight materials and miniaturized optics into their design, Schnitzer and colleagues at Howard Hughes Medical Institute solved this problem, thereby giving mice full motion capability with the microscope attached.

Tethered via fiber-optic cables to a high-speed camera that feeds images into a computer, the microscope sits directly on top of the open cranial cavity on the head of a mouse.

Injecting a fluorescent dye into the brain or bloodstream prior to imaging causes certain cells to "light up," enabling the microscope to zero in on the cells of interest. The microscope has two different-sized lenses for reaching either surface or deep-brain tissue.

Using the microscope to study brain disease could help scientists determine how neurons misfire or blood flow goes awry in conditions such as ataxia, stroke or other neuropsychiatric diseases.

The research was funded by the National Science Foundation, the Office of Naval Research, the Packard and Beckman Foundations, Stanford University, the International Human Frontier Science Program Organization and training grants from the National Institutes of Health.

Kayvon Sharghi is a science-writing intern at the Stanford News Service.

To read a recent New York Times article about related work by Mark Schnitzer, Scott Delp and others, please click here.