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One of the major goals of neuroscience is to understand how our brains are shaped by everyday experiences. The ideal way to understand that complex process is to observe the brain in action. Now, researchers at MIT have done just that – they used two-photon microscopy to visualize chemical activity in brain cells of living animals after the animals spent time in different visual environments.

“This is the first time we can look at the molecular activity inside individual cells in response to a sensory experience,” says first author Kuan Hong Wang, a research scientist at MIT who will be leading a lab at the National Institute of Mental Health in September.

Standard techniques for visualizing brain activity are limited; imaging technologies like functional MRI can show which regions of the brain are activated by experiences, but they can’t zero in on individual cells or the molecules inside those cells. Two-photon imaging, on the other hand, has the ability to detect signals made to light up individual cells in the outermost layers of the brain. To use the technique in a living mouse, scientists create small glass windows in the animal’s skull, then focus the microscope on the glass.

Past studies have used a similar technique to see how the structure of neurons changes over time (see “Old Brains Learn New Tricks”). But Wang, working in the lab of neuroscientist Susumu Tonegawa at MIT’s Picower Center for Learning and Memory, wanted to develop a way to detect cells only as they become active.

The researchers replaced a portion of a mouse gene called Arc with another gene that encodes a fluorescent protein. Arc is known to be activated in the brain by sensory input, but its specific function in the visual system is not well understood. In the engineered mice, whenever cells normally manufacture the Arc protein, they instead create a fluorescent protein that glows under the microscope’s laser light when the gene is activated. One group of mice retained one copy of the Arc gene along with the fluorescent gene, while another group received two copies of the fluorescent gene.

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