“Our dream was to invent a window into the brain, so we could see what happens inside when we’re thinking, planning, feeling, and remembering,” said Professor May-Britt Moser, discussing conversations she had as a young psychology student in the early 1990s with her long-term colleague Professor Edvard Moser.

Professor Moser is the founding director of the Center for Neural Computation and co-director of the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology (NTNU), as well as a Nobel Laureate, a title she shares with research partner, Edvard Moser, the co-director of the Kavli Institute for Systems Neuroscience.

A small mouse named “Leif Erikson” is playing a big role in their dream coming true today. Leif has aLeif Erikson equipped with the Mini2P. Source: Kavli Institute for Systems NeuroscienceLeif Erikson equipped with the Mini2P. Source: Kavli Institute for Systems Neuroscience window on his head with a 2.4 gram technological marvel that sits on top. The portable "Mini2P" is best defined as a miniature cortical observatory, capable of recording live images of brain that have never been seen before. The Mini2P can transmit live from the part of Leif's brain that controls his navigational abilities. Researchers can see twinkling brain cells on the screen as the mouse works his way toward a tower roof where Leif is rewarded with cookie crumbs.

Creating a small, revolutionary device without compromise

“If we want to understand complex behavior, the animal must be free to move and behave in a way that is natural for it,” said Edvard Moser. “The Mini2P is the first tool that allows us to study neural network activity at high resolution in naturally behaving animals.”

“When developing the Mini2P, we followed two rules where we were not willing to compromise,” said Weijian Zong. Zong is the first author of a new paper documenting the process and is a researcher at the Kavli Institute.

“The first rule was that any improvement to the equipment must not affect the animal’s natural behavior. So, we knew we had to shed weight to make the microscope and its cable as light and flexible as possible,” he said. “The second rule was that we must not compromise on the microscope’s performance. If we want researchers to invest time in a new tool, the miniscope’s features must perform significantly better than its predecessors.”

Dr. Weijian Zong, a biological engineer and neuroscientist at the Moser Group alongside the Mini2P. Source: Kavli Institute for Systems NeuroscienceDr. Weijian Zong, a biological engineer and neuroscientist at the Moser Group alongside the Mini2P. Source: Kavli Institute for Systems NeuroscienceA small electrically tunable lens is one of the Mini2P's many ingeniously engineered features. Zong was able to alter the curvature of the lens without raising the temperature by applying static voltage. Mini2P will move the focus plane between the surface and inner cell layers of the cortex when the lens' curvature is changed, allowing 3D structural recordings of brain tissue.

Help from a jellyfish glow gene

The jellyfish-inspired bioluminescence allows the researchers to see which cells are involved in particular parts of the interaction. They can also observe how the brain conversation generates ideas, which the mouse subsequently acts out "in the real world." The brain cells can also be color coded based on the genes they produce and the brain locations with which they converse. This helps researchers figure out which sorts of brain cells must work together to produce various cognitive abilities.

Mini2P is an open-source invention courtesy of the Kavli Institute. Everything needed can be obtained through GitHub.

To contact the author of this article, email ccooney@globalspec.com