Washington: Scientists have developed the first scalable method to identify different subtypes of neurons in the human brain, an advance that may provide a
better understanding of disorders such as Alzheimer's and Parkinson's.
The research lays the groundwork for "mapping" the gene activity in the human brain. By isolating and analysing the nuclei of individual human brain cells, researchers identified 16 neuronal subtypes in the cerebral cortex - the brain's outer layer of neural tissue responsible for cognitive functions including memory,
attention and decision making. "We're providing a unified framework to look at and compare individual neurons, which can help us find out how many unique types of neurons exist," said Kun Zhang, from the University of California, San Diego.
Researchers can use these different neuronal subtypes to build what Zhang calls a "reference map" of the human brain - a foundation to understand the differences between a healthy brain and a diseased brain. "In the future, patients with brain disorders or abnormalities could be diagnosed and treated based on how they differ from the reference map. This is analogous to what's being done with the reference human genome map," Zhang said. The new study reflects a growing understanding that individual brain cells are unique: they express different types of genes and perform different functions.
To better understand this diversity, researchers analysed more than 3,200 single human neurons in six Brodmann areas, which are regions of the cerebral cortex classified by their functions and arrangements of neurons. The team developed a new method to isolate and sequence individual cell nuclei. The Scripps Research Institute (TSRI) researchers led by Jerold Chun obtained the samples from a post mortem brain and focused on isolating the neuronal nuclei. Scientists at San Diego-based Illumina sequenced the resulting RNA libraries. They developed algorithms to cluster and identify 16 neuronal subtypes from the sequenced datasets. They deciphered what types of genes were "turned on" within each nucleus and showed that various combinations of the 16 subtypes tended to cluster in cortical layers and Brodmann areas, helping explain why these regions look and function differently.
Neurons exhibited many differences in their transcriptomic profiles - the patterns of genes that are being actively expressed by these cells - showing single neurons with shared, as well as unique, characteristics that likely lead to difference in cellular function. The research was published in the journal Science.
