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Brain Mapping Made Clearer With Technology

Cold Spring Harbor Laboratory Professor Anthony Zador has taken the next step in his quest to solve exactly how the brain is wired.

Starting out 10 years ago, Professor Anthony Zador and his lab studies how the brain’s circuitry mediates and control complex behaviours by mapping three pillars of brain function. The three are connectivity, gene expressions and physiological activity.

His team developed MAPseq, technique used to map the connections of different brain cells and gain abetter understanding of how they interact with each other.

In a study published in the latest issue of Cell, Zador’s lab, led by Xiaoyin Chen, a postdoctoral fellow and the first author on the paper, introduces BARseq, the next generation of MAPseq. The new technology can be used to expand the brain map by accurately pinpointing the location of a neuron. BARseq is able to determine not only a neuron’s connections, but also its pattern of gene expression and its physiological activity, two pieces of the puzzle MAPseq couldn’t handle.

“The brain is basically a circuit. It’s a bunch of neurons connected to one another,” Zador said. “In order to make progress in neuroscience, we have to actually be able to understand how those neurons are connected to one another, and ideally to be able to relate them to other aspects of neural function, like gene expression and neuronal activity.”

BARseq is designed to help researchers move closer to that goal. It’s based on the same concept as MAPseq, with several important upgrades. It solves the problem of poor spatial resolution in MAPseq that prevented researchers from pinpointing exactly where in the brain the neuron was located. With BARseq, researchers are able to tag and sequence the neurons in situ, or in their original form and location on the brain.

The team used BARseq to map the connections of 3,579 neurons in the auditory cortex of the mouse brain. Matching connectivity patterns to gene expression allows scientists to characterize different cell types and define their specific functions in the brain. It could prove to be a valuable tool for studying how neural circuits are formed.

BARseq, like its predecessor, is far less expensive, labor-intensive and time-consuming than current mapping technologies. His lab used it to map up to tens of thousands of neurons per animal in a few weeks at a relatively low cost.

The team is now refining BARseq to achieve synaptic resolution for even clearer and more accurate mapping. While BARseq can pinpoint exactly where a neural connection begins, it can only provide a close estimate of where it ends. [APBN]