1-gram wireless microscope records 8,500 neurons in mice

A mouse runs, climbs and socializes, and the scientists watching its brain are, until now, working with a tether or a head held still. That constraint has shaped what neuroscience could see. A team from Tsinghua University and the Chinese PLA Medical School has built a wireless microscope that lets the animal move much more freely. The device, called Airscope, weighs 1 gram without its battery, and in a paper published in Nature the researchers report that it can image more than 8,500 neurons across a mouse's cortex, the outer layer of the brain.

To understand why the weight matters, it helps to know how these instruments work. Calcium imaging tracks neurons through a fluorescent signal that brightens when a cell fires, so a microscope that sees many cells at once can show how groups of neurons behave during an action. Conventional head-mounted microscopes of this kind typically weigh more than 3 grams, and the earlier wireless versions were too heavy and offered a narrower view. Airscope pairs a 2-megapixel sensor with just four aspheric lenses, a shape that the researchers say makes the device 2.84 times shorter than previous miniaturized microscopes while matching the neuron yield of benchtop mesoscopes. It images at single-cell resolution, about 4 micrometers, across a 6-millimeter (0.24-inch) field of view at 12.5 frames per second. Data compression lets it send megapixel images wirelessly, and a magnetically attached battery that can be swapped supports long recordings.

The team tested the device in mice living in a habitat of about 5 square meters (54 square feet) and in a large maze with 32 terminal arms. Cortical activity changed systematically with the terrain the mice crossed, according to Wu Jiamin of Tsinghua. In other experiments described in the paper, activity patterns across the dorsal cortex correlated with behavioral signs of social dominance, and population activity could predict which of two mice would win a competition. With two Airscopes on one animal, the researchers recorded the brain and spinal cord together during fear conditioning, and characterized the influence of the spinal cord on the cortex. Zhang Yuanlong, an assistant professor at Tsinghua, said the device lets animals move more freely, so that large-scale recordings can accompany a wider range of natural behaviors.

For neuroscientists, the gain is the ability to record large populations of neurons in animals doing something other than sitting still. The paper's authors say the recordings stay stable from the same region for more than 200 days, with signal quality comparable to a conventional benchtop microscope. The limits are real: every result described so far comes from mice. Dai Qionghai, the paper's corresponding author, said the device could later extend to immunology and oncology, enabling tracking of disease progression, but that is a direction the team has named, not a result it has shown.

For now, the immediate beneficiaries are research groups that study how behavior emerges from neural activity. Airscope gives them a way to record the brain in natural settings, where earlier tools forced a choice between precision and movement. The next test is whether other laboratories can reproduce these recordings, and the Nature version, still an early online release, is the document to read until final publication.