17 September, 2025
mini-microscope-revolutionizes-3d-brain-imaging-in-mice

Researchers at the University of California, Davis, have developed a groundbreaking miniaturized microscope that enables real-time, high-resolution, noninvasive imaging of brain activity in freely moving mice. This innovation marks a significant advancement in neuroscience, potentially transforming the study of brain function and behavior.

“What we are doing is creating technology to image brain activity in freely moving and behaving mice to open up the behavior paradigm,” said Weijian Yang, professor of electrical and computer engineering at UC Davis. “The goal is to create a device capable of enabling research into brain activity and behavior in mice in real time—to see how brain activity drives behavior or perception.”

The new device, known as DeepInMiniscope, is expected to provide profound insights into brain function, ultimately benefiting human health by facilitating the development of novel therapeutic strategies for brain disorders. This first-of-its-kind imaging system was detailed in a paper published on September 12 in the journal Science Advances.

Innovative Design and Functionality

DeepInMiniscope builds upon Yang’s earlier work on lensless cameras capable of producing three-dimensional images from a single exposure. While previous systems were effective for large objects in low light-scattering environments, they struggled with the complexities of biological samples. In living tissue, prevalent light scattering and low signal contrast posed significant challenges.

To overcome these obstacles, DeepInMiniscope incorporates a novel mask design featuring over 100 miniaturized, high-resolution lenslets. A unique neural network synthesizes images from each lenslet to reconstruct detailed 3D images.

Deep Learning Integration

The neural network employed by DeepInMiniscope integrates various machine learning techniques to form an unrolled neural network. This allows for instantaneous, accurate, and high-resolution reconstruction of intricate details across a large 3D volume. Yang and his team have successfully recorded neuronal activity in mice in real time using this tool.

“Our algorithm combines interpretability, efficiency, scalability, and precision,” said Feng Tian, a postdoctoral researcher in Yang’s lab and the first author of the corresponding paper. “It requires only a minimal amount of training data, yet it can robustly and accurately process large-scale datasets at high speed.”

Design and Practical Application

The mini microscope’s design is both compact and ergonomic, allowing it to be comfortably worn by mice as they move freely. Measuring just 3 square centimeters—approximately the size of a grape—and weighing around 10 grams, equivalent to four pennies, DeepInMiniscope is nearly optimized for practical use.

Previous designs were limited by the bulkiness of traditional cameras, but DeepInMiniscope utilizes a sensor as compact as a bare circuit board with an image sensor, eschewing the need for a self-contained and enclosed system. Yang envisions a future iteration of the device measuring just 2 square centimeters, akin to a hat for a mouse, and aims to make it cordless.

Implications for Neuroscience

The development of DeepInMiniscope represents a significant leap forward in neuroscience research. By enabling real-time observation of brain activity in freely moving mice, scientists can gain a deeper understanding of how neural processes influence behavior and perception. This could pave the way for breakthroughs in the treatment of neurological disorders in humans.

As the technology continues to evolve, it holds the promise of expanding the horizons of behavioral neuroscience, offering researchers unprecedented tools to explore the complexities of the brain. The implications for both basic science and clinical applications are vast, potentially leading to new methods for diagnosing and treating brain-related conditions.

As Yang and his team continue to refine the device, the scientific community eagerly anticipates the next steps in this exciting journey. The potential for DeepInMiniscope to revolutionize brain research is immense, and its impact on the field could be profound.