Miniscope offers window-like view of brain functions in action

Thanks to ever-advancing technology, we know a lot about the inner workings of the brain. However, there is so much yet to be discovered and getting a look at the neurons, cells, and circuits in action within the brain’s cortex will help. This could be possible, thanks to a miniature microscope offering a first-hand view.

The Mini2P—developed by a team at the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Norway (NTNU)—is similar to a standard light microscope, with lasers to excite and register neurons very precisely and at high resolution.

The new device features a tiny electrically tunable lens, the curvature of which researchers can manipulate via static voltage without causing a rise in temperature. Used on a mouse model, the Mini2P shifted the focal plane between the surface and deeper cell layers within the brain’s cortex, thanks to the lens’ curvature.

The new miniscope produces 3D structure recordings of brain tissue, and can also record along multiple planes in the Z-axis (toward the top of the brain, ranging from axonal branches—substructures of cells—to topographical maps of thousands of cells), in several regions: memory, navigation, and the visual area. It mapped large neural landscapes, including 10,000 brain cells within the visual cortex.

The Mini2P device, when attached to the top of the animal’s head, weighs just 2.4 grams; the laser within it is flexible, which allows the subject to move freely, as it would naturally. Existing microscope technology for brain imaging is large and bulky and doesn’t allow for natural movement, which limits the potential outcomes with this type of study.

The mouse’s navigational skills were observed as it performed various tasks, including walking across the floor and climbing a tower. Its activity became visible in its brain as cells illuminated, thanks to a gene borrowed from jellyfish, which makes the brain cells light up as they talk to each other. This allows the researchers to see which cells interact with each other. Based on this, they color-coded the brain cells, and learned which brain cells must collaborate to generate different cognitive abilities.

“If we want to understand complex behavior, the animal must be free to move and behave in a way that is natural for it,” says Dr. Edvard Moser, a Nobel Laureate, professor and founding director of the Kavli Institute for Systems Neuroscience, and codirector of NTNU’s Center for Neural Computation. “The Mini2P is the first tool that allows us to study neural network activity at high resolution in naturally behaving animals."

Via miniscope, brain cells can be monitored for over a month, which allows more comprehensive exploration of various areas and functions throughout the cortex. It could also help researchers study brain diseases such as Alzheimer’s in the future.

“Alzheimer’s disease often starts with damage in the entorhinal cortex,” Moser says. “We know that Alzheimer’s causes deficits in the ability to navigate, and in memory. The ability to label different cell types, may enable us to identify which cells are vulnerable to the early changes related to Alzheimer’s disease.”