A One-Gram Wireless Microscope Records 8,500 Neurons in a Freely Moving Mouse

October 20 — According to Xinhua, Chinese scientists have built what is currently the world’s lightest wireless mesoscopic microscope. Weighing just 1 gram, it can record neural activity in the mouse cortex at single-cell resolution across a 6-millimetre field of view, capturing more than 8,500 neurons in a single mouse at once — 25 times as many as comparable existing devices. The work was published online in the journal Nature on the evening of the 19th.

Recording large numbers of neurons across large brain regions at single-cell resolution while several animals move and socialise freely could reveal how the brain controls complex behaviour. However, existing microscopes that resolve individual neurons, even when they can see large areas of cortex, still require the mouse’s head to be fixed under the instrument or tethered by a cable — which makes it hard for the animal to move freely and obstructs studies of neural activity and behaviour in natural conditions.

A team led by Dai Qionghai, an academician of the Chinese Academy of Engineering and a professor at Tsinghua University, working with Dai Pu’s team at the Chinese PLA General Hospital, used integrated design and systematic optimisation to build the ultra-light wireless mesoscopic microscope Airscope. With only four aspheric lenses, it achieves single-cell resolution (4 to 6 micrometres) across a 6-millimetre field of view.

“Wireless, lightweight, wide-field and high-throughput are Airscope’s distinguishing features,” said Wu Jiamin, an associate professor in Tsinghua’s Department of Automation. Conventional head-mounted miniature microscopes usually weigh more than 3 grams, which affects the mouse’s freedom of movement. Airscope not only frees the animal from cables and is lighter, but also uses a 2-megapixel image sensor to compress data at the device’s edge, allowing megapixel images to be transmitted wirelessly.

With this device, which the animals can wear, the team unlocked many kinds of complex free exploration by mice in natural conditions, completing experiments that were previously hard to do because of cables or device weight. For example, they recorded cortical activity in several mice exploring a natural habitat of 5 square metres at the same time, and tracked mice exploring autonomously for long periods in a large maze with 32 endpoints. The study found that cortical activity changes systematically with the type of terrain the mouse is in.

The new microscope provides a tool for understanding the neural basis of intelligence and will push optical brain-computer interfaces towards more precise neural probing. In future, its applications may extend from neuroscience to fields such as immunology and oncology, enabling complete tracking of how disease develops.