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Rebuilding the brain's circuitry
Date:11/24/2011

gnaling. Here we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function."

The two other senior authors on the paper are Jeffrey Flier, dean of Harvard Medical School, and Matthew Anderson, HMS professor of pathology at BIDMC.

The findings are to appear Nov. 25 in Science.

In 2005, Jeffrey Flier, then the George C. Reisman professor of medicine at BIDMC, published a landmark study, also in Science, showing that an experimental drug spurred the addition of new neurons in the hypothalamus and offered a potential treatment for obesity. But while the finding was striking, the researchers were unsure whether the new cells functioned like natural neurons.

Macklis's laboratory had for several years developed approaches to successfully transplanting developing neurons into circuitry of the cerebral cortex of mice with neurodegeneration or neuronal injury. In a landmark 2000 Nature study, the researchers demonstrated induction of neurogenesis in the cerebral cortex of adult mice, where it does not normally occur. While these and follow-up experiments appeared to rebuild brain circuitry anatomically, the new neurons' level of function remained uncertain.

To learn more, Flier, an expert in the biology of obesity, teamed up with Macklis, an expert in central nervous system development and repair, and Anderson, an expert in neuronal circuitries and mouse neurological disease models.

The groups used a mouse model in which the brain lacks the ability to respond to leptin. Flier and his lab have long studied this hormone, which is mediated by the hypothalamus. Deaf to leptin's signaling, these mice become dangerously overweight.

Prior research had suggested that four main classes of neurons enabled the brain to process leptin signaling. Postdocs Artur Czupryn and Maggie Chen, from Macklis's and Flier's labs, respec
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-960-7221
Harvard Medical School
Source:Eurekalert

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