Lightweight microscope captures large-scale brain activity in moving mice

As a mouse explores its environment, millions of neurons throughout its brain fire in sync: studying only a small part at a time is like missing the forest for the trees, but powerful microscopes that could capture an entire mouse brain simultaneously would be too heavy to be attached to a moving mouse.

Now, a new study published in Nature Biomedical Engineering offers an innovative solution to this problem: a microscope that weighs just the size of a dime but can capture wide-area brain activity with unprecedented resolution. “The ability to observe the brains of mice as they engage in natural behaviors such as social interaction and prey capture will improve our understanding of how neural activity distributed throughout the brain relates to natural behaviors,” says study leader Alipasha Bazili of Rockefeller University.

Mouse-sized microscope

Any large mammal can be fitted with a standard head-mounted microscope, and even a mouse can be fitted with the technology, which weighs about 20 grams, or the size of an 8-cent coin. But mice, which are often used as a model organism for understanding how the brain works, are much smaller: a microscope designed to fit a mouse would have to weigh less than 3 grams.

“While there has been an explosion of head-mounted microscopes for mice in recent years, they typically only support imaging a field of view of a few hundred micrometers at cellular resolution, as larger fields of view require designs that are too complex and unbearably heavy to support,” says Vaziri. Existing models that are light enough for a mouse to carry necessarily compromise the microscope's field of view, resolution, depth range (or a combination of these) and are prone to motion artifacts.

Previous attempts to overcome this limitation have focused on making existing technology lighter, for example by replacing metal parts with plastic, while keeping the basic optical design of a microscope (especially one that can capture a wide field of view), where heavy lenses make up the majority of the weight. Vaziri approached this challenge with what he calls a “principled approach.” Rather than trying to reduce the weight of a complex lens-based system, he defined what the real goal of this technology was: to solve the high-resolution mapping problem between points in the 3D volume of the sample and points on the 2D surface of the camera. With that in mind, he set out to create a lightweight system that met those goals without being bound by the need to adapt to an image-preserving lens-based system.

“Everyone was taking these multi-element, heavy lenses and trying to make them lighter,” says Vaziri. “Instead of figuring out how to make lenses lighter, we solved the opposite problem and developed a strategy that essentially doesn't use lenses, circumventing the problem by freeing ourselves from the unnecessary constraints of lens-based image formation.”

New thinking = new approach

Enter Diffractive Optical Elements (DOEs). While traditional lenses use a continuously curved surface to generate a spherical curvature of the wavefront, DOEs use microstructures to manipulate light through diffraction, allowing precise control of light waves. DOEs are small, lightweight, and effective. In microscopy, the function of a traditional lens is to map points in space on an object to an image plane (such as a camera sensor) so that the image formed resembles the real scene. However, to achieve larger and larger fields of view while maintaining resolution, errors introduced by single lenses (optical aberrations) increase the number of lens elements, necessitating compound lens designs.

The Vaziri lab has demonstrated that the DOE can be used to accurately map the location between the scene and the sensor without forming an image, and then use computational methods to reconstruct the original scene.

Without heavy compound lenses, the miniature microscope weighs just 2.5 grams and can image a large area of ​​a mouse brain with a field of view of 3.6 x 3.6 mm², with a lateral resolution of 4 μm, a depth of field of 300 μm, and a recording rate of 16 volumes per second. And most of the parts can be 3D printed or leverage inexpensive consumer cell phone camera sensors. “If any lab is interested, they can build these microscopes easily and at low cost,” says Vaziri.

Future versions of the miniature microscope could include wireless data transmission capabilities (current models come with cables that don't get in the way of a single mouse, but can easily get tangled when observing multiple mice interacting with each other) as well as tweaks to the technology that allow it to look at areas of the brain deeper in the cortex.

“This system comes with some sacrifices and is not as powerful as a larger microscope,” Vaziri says, “but it is an important innovation, and one that could only be achieved by bringing new ways of thinking to the problem and breaking free from perceived constraints.”

Sources 1/ https://Google.com/ 2/ https://www.sciencedaily.com/releases/2024/06/240626151913.htm The mention sources can contact us to remove/changing this article

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