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New tools to probe cell types in the brain

March 4, 2015

One of the most powerful ways to learn about the brain is to target specific types of cells and learn how their genes and behaviors contribute to the function of circuits. Scientists at the Allen Institute are working to catalog the thousands of different types of cells in the brain, often using techniques that manipulate the genes of a small subset of cells so that the cells glow under fluorescent microscopes.

"While there are thousands of types of cells, the tools we have are often not specific enough to identify just one cell type,” explains Hongkui Zeng, Senior Director of Research Science at the Allen Institute. "If you want to find a few needles in a haystack, you can hold a magnet over the pile and pull out just the metallic pieces. In the case of neurons, we need to first make them stand out enough to be picked up by our microscopes. We do this by manipulating unique gene markers for each cell type into fluorescent labels or probes, so that the structure and function of this cell type can be visualized and studied."

As Zeng and her team report in the latest issue of Neuron, scientists at the Allen Institute have created an exciting and expansive new set of tools, including genetically altered mouse lines and viruses that can activate targeted genes, which make it much more feasible for scientists to study many new types of cells. They accomplished this in part by creating a system that relies on manipulating not just one, but two or more genes at a time, in order to increase the specificity of the types of cells studied.

"We want to understand the neural code, that is, how the brain encodes information about the external world," explains Aleena Garner, scientist at the Allen Institute, "so having methods that let us monitor the activities of many different types of cells in a consistent manner is key to studying the roles of these cells in processing information and driving the animal's behavior."

Another exciting facet of these new tools, beyond making certain cell types fluorescently glow, is the ability to use light to make the cells actually fire a signal, using a technique called optogenetics.

"The combination of fluorescent imaging and optogenetic stimulation is a powerful way to learn both where cells are in space, when they are active or silent, and how they interact with other cells in the circuits they form," says Zeng." The new tools we have created open doors to identifying and learning more about the many different types of cells in our brains: the first crucial step to understanding how information is encoded by neural circuits."

The work reported in the Neuron article is a result of collaborations between Allen Institute scientists and researchers at University College London, MIT, Imperial College London, University of Otago, University of Zurich, RIKEN Brain Science Institute, and Mount Sinai Hospital.

For more information, see the video abstract on Neuron's YouTube page. The Neuron paper is also free to download until April 23, 2015 via this link.

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