Researchers create 1-gram microscope for precise neural detection

Beijing (ANTARA) — A team of Chinese scientists has developed a wireless microscope weighing just one gram that can record neural activity in the cerebral cortex of mice at single-cell resolution in natural environments.

Named Airscope, the device was developed by a team led by Dai Qionghai, an academician of the Chinese Academy of Engineering and a professor at Tsinghua University, in collaboration with researchers from other institutions. Details of the achievement were published in the journal Nature, according to Xinhua.

Dai said the microscope provides a new tool for understanding the neural basis of intelligence and will advance optical brain–computer interfaces towards more precise neural detection. Its future applications could extend beyond neuroscience to fields such as immunology and oncology, enabling comprehensive tracking of disease processes, Dai added.

How the brain regulates behaviour in complex natural environments is one of the most fundamental questions in neuroscience and is crucial to understanding intelligence and developing brain–computer interfaces. However, research in this area has long been constrained by a trade-off between the neural observations achievable in freely moving animals and the weight of the microscope.

Studying how the brain regulates behaviour in natural environments requires the simultaneous recording of large numbers of neurons across different brain regions at single-cell resolution, while the animals are able to move and interact socially.

Existing microscopes capable of visualising individual neurons still require instruments to be attached to a mouse’s head or the animal to be connected by cables. This makes it difficult for the animals to move freely and hinders the study of neural and behavioural processes in natural conditions.

At the same time, existing head-mounted microscopes that allow animals to move freely usually have a field of view of less than 1 mm, revealing only a small part of the brain. Covering a wider cortical area at higher resolution has required heavier microscopes that consume more power.

By resolving this dilemma, researchers can observe how thousands of neurons work together to support behaviour in conditions closer to real life. This opens new avenues for understanding the neural basis of intelligence and provides a new tool for large-scale neural signal recording in optical brain–computer interfaces.

One gram

Through an integrated design and systematic optimisation, Airscope weighs just one gram and achieves single-cell resolution of about 4 to 6 micrometres across a 6 mm field of view.

Airscope can be mounted directly on a mouse’s head and uses a 2-megapixel image sensor to compress data on the device, enabling megapixel-resolution images to be transmitted wirelessly.

Experiments showed that mice wearing Airscope could climb ropes and pass through narrow tubes, with no significant differences in distance travelled, speed or path tortuosity compared with mice not wearing the device.

The quality of the neuronal signals recorded by Airscope was comparable to that captured by conventional benchtop microscopes. Combined with a neuron-extraction algorithm previously developed by the team, Airscope can simultaneously record more than 8,500 neurons across 14 cortical areas in one hemisphere of a mouse’s brain — about 25 times more than existing wireless imaging devices. It can record from the same location for more than 200 days.

Using the wearable device, the research team revealed complex forms of free exploration by mice in natural conditions and completed experiments that had previously been difficult because of cables or equipment weight.

These included simultaneously recording cortical activity in several mice exploring a 5-square-metre naturalistic habitat, and tracking mice during long periods of autonomous exploration in a large maze with 32 endpoints.

Standard laboratory cages make it difficult for mice to display natural behaviours such as digging, travelling long distances and engaging in complex social interactions. The researchers instead built a 5-square-metre habitat featuring shelters, slopes, tree holes, wooden huts and other terrain features. There, mice moved more than twice as fast as they did in their cages and displayed 16 categories of behaviour, including climbing, going up and down stairs, entering holes and crossing different types of terrain.

The study found that cortical activity changed systematically according to the terrain area in which the mice were located. Using only cortical neural activity, a deep-learning model could identify the animals’ location with accuracy substantially above chance.

“Airscope gives animals greater freedom of movement for neuroscience research and allows large-scale neural observations to follow them into a wider range of natural behaviours, helping us better study brain cognition and disease,” said Zhang Yuanlong, a lecturer in Tsinghua University’s School of Life Sciences.