Cell: develop barseq technology to build a better brain map

October 24, 2019 Professor Anthony Zador and his team have been studying how brain circuits mediate and control complex behaviors Ten years ago, they drew three pillars of brain function: connectivity, gene expression and physiological activity Because there is no effective technology to do this, his team developed mapseq, a technology to map the connections between different brain cells and better understand how they interact with each other Over the years, Zador and his lab have continued to improve the technology In a new study, led by postdoctoral researcher Xiaoyin Chen, Zador lab introduced the next generation of mapseq Technology: barseq This new technology can be used to expand the brain map by pinpointing the location of neurons This enables barseq to determine not only the connections of neurons, but also their gene expression patterns and physiological activities, which are two problems that mapseq cannot solve The relevant research results are published in the cell Journal on October 17, 2019, and the paper title is "high throughput mapping of long range neural project using in situ sequencing" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.09.023 "The brain is basically a circuit," said Zador It's a group of interconnected neurons In order to make progress in the field of neuroscience, we must actually be able to understand how these neurons are connected to each other and, ideally, to relate them to other aspects of neural function, such as gene expression and neuronal activity " Barseq aims to help people get closer to this goal It is based on the same concept as mapseq and has made some important upgrades The researchers used mapseq to label each neuron with a unique barcode made up of genetic sequences By tracking these markers in the brain, they can see where these neurons send messages and then map the pathways that these signals form between different regions of the brain This is called brain connectivity The problem with mapseq is that in the process of labeling these neurons, the brain cells must be mixed together, then separated and labeled, which will lead to poor spatial resolution The process produces a fuzzy map, making it difficult for scientists to see how neurons are linked to specific brain functions, such as gene expression This low resolution also prevents people from accurately locating neurons in the brain Barseq solves this problem by allowing scientists to label neurons in situ "So basically, when we sequence these barcodes, we can see exactly where these neurons are," Chen said The researchers used barseq to map the connections of 3579 neurons in the auditory cortex of mice Matching connectivity patterns with gene expression allows scientists to characterize different cell types and determine their specific functions in the brain This will prove to be a valuable tool for studying how neural circuits are formed "If we can have a complete linkage map, it can lay the foundation for understanding thoughts, consciousness, decision-making and how these errors occur in autism, schizophrenia, depression, obsessive-compulsive disorder and other neuropsychiatric diseases," said Zador Like its predecessor, barseq is cheaper, labor-saving and time-saving than the current mapping technology His lab used it to construct a map of thousands of neurons in each animal in a few weeks at a relatively low cost The researchers are now refining barseq to produce a clearer and more accurate map of the brain at synaptic resolution Although barseq can accurately determine the starting point of neural connection, it can only provide a very close estimate of its end point "For now, I can tell you where a neuron sends its axons, but I can't tell you exactly which neurons it synapses with," said Zador We still don't have enough spatial resolution at the destination However, we are trying to solve this problem " (BIOON Com) reference: 1 Xiaoyin Chen et al High throughput mapping of long range rural project using in situ sequencing Cell, 2019, DOI: 10.1016/j.cell.2019.09.023 2 Barseq buildings a better brain map https://mediaexpress.com/news/2019-10-barseq-brain.html