Tiny Head-Mounted Microscope Rides Along As Mice Go About Their Business

80beatsBy Valerie RossSep 15, 2011 9:49 PM

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 A new thumbnail-sized microscope will give researchers a way to see what's happening in the brain of a mouse as it moves around and goes about its business. The microscope, described earlier this week in Nature Methods, weighs less than 2 grams---little enough that it can be fitted atop a rodent's head---and tracks the activity of up to 200 brain cells. What's the Context:

What's the News:

  • To watch a living brain in action, researchers usually have to make sure the animal that brain belongs to is keeping very still, be it a human in an MRI machine or a mouse under a benchtop microscope. That's not such a problem for researchers studying, say, vision or memory---but it's difficult to investigate the neuroscience of movement or behavior when your subjects can't move around and behave.

How the Heck:

  • The new device is a fluorescence microscope, meaning it shines light on a sample, then captures the glow that bounces back. Despite the scope's tiny size, the researchers fit all the necessary optical components---lenses, sensors, a mirror, an LED light, and more---inside it.

  • In addition to being mobile, the microscope captures the activity of more cells than a traditional benchtop microscope does, letting researchers see what's happening in a larger area of the brain.

  • To test out this new tool, the researchers cut small holes in the skulls of lab mice, then mounted the microscope, top hat-like, on the mice's heads. For this study, they placed the scope over the cerebellum, the brain area involved in motor coordination.

  • The team injected the mice with a fluorescent dye that stuck to particular molecules in the brain and glowed under the LED light, providing a real-time feed of what the cells were doing. They then set the mice free to walk around a small enclosure or run on a wheel, recording their brain activity all the while. The video below shows the mice moving around on the left, and their concurrent brain activity---captured by the microscope---on the right.

The Future Holds:

  • "For the animal to be able to carry the whole microscope along with it opens a lot more possibilities in studying behavior," bioengineer Daniel Fletcher, who wasn't involved with the study, told Technology Review.

  • While the prototype of the microscope cost $50,000 to make, all of the optical components either are or easily could be mass produced, which could vastly decrease the price.

  • The researchers see possibilities for this portable, soon-to-be-affordable microscope beyond neuroscience research, such as using it for diagnostic tests in areas without advanced medical facilities.

Reference: Kunal K. Ghosh et al. "Miniaturized integration of a fluorescence microscope." Nature Methods, published online September 11, 2011. DOI: 10.1038/nmeth.1694Image courtesy of Dan Stober, Stanford News Service / Video courtesy of Ghosh et al, Nature Methods

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