New Microscope Enhances View of Neural Circuits

Picower Institute at MIT

The brain's ability to learn comes from "plasticity," in which neurons constantly edit and remodel the tiny connections called synapses that they make with other neurons to form circuits. To study plasticity, neuroscientists seek to track it at high resolution across whole cells, but plasticity doesn't wait for slow microscopes to keep pace and brain tissue is notorious for scattering light and making images fuzzy. In a paper in Scientific Reports, a collaboration of MIT engineers and neuroscientists describes a new microscopy system designed for fast, clear, and frequent imaging of the living brain.

The system, called "multiline orthogonal scanning temporal focusing" (mosTF), works by scanning brain tissue with lines of light in perpendicular directions. As with other live brain imaging systems that rely on "two-photon microscopy," this scanning light "excites" photon emission from brain cells that have been engineered to fluoresce when stimulated. The new system proved in the team's tests to be eight times faster than a two-photon scope that goes point by point, and proved to have a four-fold better signal to background ratio (a measure of the resulting image clarity) than a two-photon system that just scans in one direction.

"Tracking rapid changes in circuit structure in the context of the living brain remains a challenge," said co-author Elly Nedivi, William R. (1964) and Linda R. Young Professor of Neuroscience in The Picower Institute for Learning and Memory and MIT's Departments of Biology and Brain and Cognitive Sciences. "While two-photon microscopy is the only method that allows high resolution visualization of synapses deep in scattering tissue, such as the brain, the required point by point scanning is mechanically slow. The mosTF system significantly reduces scan time without sacrificing resolution."

Scanning a whole line of a sample is inherently faster than just scanning one point at a time, but it kicks up a lot of scattering. To manage that scattering, some scope systems just discard scattered photons as noise, but then they are lost, said lead author Yi Xue

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