A New Microscope

Researchers develop a two-photon microscope that provides the unprecedented brain-imaging ability. 

By James Badham

 

December 7, 2021
Spencer Smith
Spencer Smith

Advancing our understanding of the human brain will require new insights into how neural circuitry works in mammals, including laboratory mice. These investigations require monitoring brain activity with a microscope that provides resolution high enough to see individual neurons and their neighbors.

Two-photon fluorescence microscopy has significantly enhanced researchers’ ability to do just that, and the lab of Spencer LaVere Smith, an associate professor in the Department of Electrical and Computer Engineering at UC Santa Barbara, is a hotbed of research for advancing the technology. As principal investigator on the five-year, $9 million NSF-funded Next Generation Multiphoton Neuroimaging Consortium (Nemonic) hub, which was born of President Obama’s BRAIN Initiative and is headquartered at UCSB, Smith is working to “push the frontiers of multi-photon microscopy for neuroscience research.”

In the Nov. 17 issue of Nature Communications, Smith and his co-authors report the development of a new microscope they describe as “Dual Independent Enhanced Scan Engines for Large Field-of-view Two-Photon imaging (Diesel2p).” Their two-photon microscope provides unprecedented brain-imaging ability. The device has the largest field of view (up to 25 square millimeters) of any such instrument, allowing it to provide subcellular resolution of multiple areas of the brain. 

“We’re optimizing for three things: resolution to see individual neurons, a field of view to capture multiple brain regions simultaneously, and imaging speed to capture changes in neuron activity during behavior,” Smith explained. “The events that we’re interested in imaging last less than a second, so we don’t have time to move the microscope; we have to get everything in one shot, while still making sure that the optics can focus ultrafast pulses of laser light.”

 

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