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Entirely New Way To Study Brain Function Developed

Entirely New Way To Study Brain Function Developed

BrainScientists at Duke University and the University of North Carolina have devised a chemical technique that promises to allow neuroscientists to discover the function of any population of neurons in an animal brain, and provide clues to treating and preventing brain disease.

"We have discovered a method in which systemic administration of an otherwise inert chemical to a mutant mouse selectively activates a single group of neurons," said James McNamara, M.D., chairman of the Duke Department of Neurobiology and co-senior author of the paper.

"Elaborating on this method promises to let scientists engineer different kinds of mutant mice in which single groups of neurons will be activated by this chemical, so scientists can understand the behaviors mediated by each of these groups."

Right now, most scientists gain knowledge of brain function by correlating brain activity with certain behaviors; connecting a damaged brain area with an observed loss of function; or activating entire brain structures invasively and observing the resulting behavior.

Knowing what a particular type of neuron in a specific brain region does will help researchers find the root of certain diseases so they can be effectively treated, said McNamara, an expert in epilepsy. He pointed out that the human brain contains billions of neurons that are organized into thousands of distinct groups that need to be studied.

Four years ago, co-senior author Bryan Roth, M.D., Ph.D., and colleagues at UNC set out to create a cell receptor activated by an inert drug, but not by anything else. "Basically we wanted to create a chemical switch," said Roth, who is the Michael Hooker Distinguished Professor of Pharmacology at UNC-Chapel Hill.

"We wanted to put this switch into neurons so we could selectively turn them on to study the brain," said Roth, who was trained as a psychiatrist. "At the time, this idea was science fiction."

They used yeast genetics to evolve a specific receptor that could react with a specific chemical, because yeast quickly produces new generations. "If the theory of evolution were not true, this experiment would not have worked," Roth added.

The lab then worked to create a similar receptor in mice. In the initial attempt to create mice that expressed the receptor, the lab targeted receptor expression to neurons in the hippocampus and cortex of the brain. The receptor was designed to be activated by the drug clozapine-N-oxide (CNO), which has no other effects on the mice and no effects on normal neurons, those without the receptor.

Source: Duke University Medical Center

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