Mini microscopes embedded into the brains of genetically engineered mice are providing researchers a window onto the inner workings of the mammalian mind.
The tool provides an unprecedentedly wide field of view on the mouse brain – in one mouse, for example, the team recorded the firing of more than 1,000 individual neurons – and it can record for weeks on end, allowing scientists to study how brain activity evolves over time.
“That kind of question, the time-lapse question, has not been previously examined in freely behaving mice,” Mark Schnitzer, an associate professor of biology and applied physics at Stanford University, told NBC News.
He and colleagues described the tool earlier this month in the journal Nature Neuroscience and have launched a startup company, Inscopix Inc., to market the mini microscopes to researchers who study neurodegenerative diseases such as Alzheimer’s and other brain disorders.
The mini microscopes are mounted into little circles removed from the mouse cranium. They wear them around like a hat, Schnitzer explained.
Neurons in the mice’s hippocampus, a region of the brain associated with spatial memory, are genetically engineered to express green fluorescence protein, especially in the presence of calcium. When a neuron fires, the cell naturally floods with calcium ions, and thus fluoresces more intensely.
The mini microscope is connected to a camera chip, which routes images of neurons fluorescing to a computer screen. The result is a near real-time video of the mouse’s brain activity as it runs around a small enclosure. Check it out in the video below.
To the untrained eye, the firing neurons appear chaotic and random, but the researchers discerned a clear pattern. Specific neurons fire in association with specific areas in the enclosure.
“The individual neurons seem to have preferences regarding the mouse’s location in space,” Schnitzer explained. “This neuron might fire when the mouse is over here and that neuron might fire when the mouse is over there.”
While this spatial mapping was known from previous studies, the ability to image many hundreds of neurons at once and for long enough to watch the brain evolve is novel, Schnitzer said. The tool may come in handy for researchers studying the evolution of diseases such as Alzheimer’s.
For example, the National Institutes of Health has supported the development of mouse models of human brain diseases, Schnitzer explained. Using the tool, researchers could compare the evolution of a healthy mouse with one known to have a model of Alzheimer’s.
This might, Schnitzer said, allow researchers to “see maybe what early symptoms look like before it is even apparent at the behavioral level. And one could imagine providing therapeutics and seeing the effects of those down to the resolution of single cells.”