Method Developed by Children’s Hospital Los Angeles Researchers Automates Brain Cell Mapping

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Neuroscience graduate students at Children’s Hospital Los Angeles have developed an automated method that could save time and work for laboratories around the country by streamlining the process of identifying and mapping brain cells. Scientists want to understand how brain cells develop over time because the way these cells, called neurons, develop influences how they function, or how they malfunction in neurodevelopmental disorders.

To understand how children’s brains develop, and how this development goes awry in disorders such as autism, neuroscience researchers catalog various brain cells by their function and where they are located in tissues. Mapping these cells can help scientists understand how different types of neurons interact in networks to direct brain functions. This basic research could eventually be used to guide therapies for various neurodevelopmental disorders.

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“At least when it comes to the brain, there is a spatial organization,” says Ramin Ali Marandi Ghoddousi, a PhD candidate in neuroscience who researches early brain and motor development in the Levitt Laboratory. “Certain cell types reside in one part of the tissue and other cell types in other parts. Sometimes they are interspersed with each other. But where they are found in the tissue implicates the different neuron functions.”

“There are tens of thousands of different cell types,” says Pat Levitt, PhD, Senior Vice President, Chief Scientific Officer and Director of The Saban Research Institute at Children’s Hospital Los Angeles. “Which kind of neurons in the brain are expressing certain genes? In the brain, anatomy is everything.”

Aside from location, scientists also categorize cells by the genes they express — in particular, their messenger RNA (mRNA), which carries genetic information from the DNA in a cell’s nucleus to its cytoplasm where the instructions are read and translated into the proteins that direct the cell’s development and function.

Researchers use a standard method to identify cells, called multiplex fluorescent in-situ hybridization, or mFISH. This technique stains the mRNA within cells with a fluorescent probe that induces the genetic material in the cells to light up under a microscope–rather like a scattering of holiday lights. The illuminated mRNA can help identify the type of cell. Some commercial multiplexing methods can characterize up to 40 genes at a time in a tissue section.

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