“It was a pretty simple idea, but important,” Dan says about the work, published June 7, 2012, in Nature. The experiments support a long-standing model of how the mammalian cortex is organized, she explains. In the 1950s, scientists discovered that the neurons in the cortex are organized in columns, somewhat like the ribs of a fan, with each column responding to a particular type of stimulus. When Pasko Rakic at Yale University found that sister neurons also line up in columns that parallel the functional columns, he proposed that the developmentally related columns form the basis of the functional ones and dubbed it “the radial unit hypothesis.”

The work from Dan’s team, done in collaboration with Shi’s group in New York, is the first hard evidence supporting that model. “There were some hints, but this was proof in the intact system,” Dan says. “Columnar organization really talks about the function, and that is something you can look at only in live animals.”

Dan continues to explore how neurons work together in the mammalian brain. Her team recently turned its sights on inhibitory neurons, which modulate how other neurons respond to a stimulus. They reported in the August 16, 2012, issue of Nature that of three molecularly identifiable types of inhibitory neurons in the visual cortex, one type helps fine-tune the range of stimuli that its partner neurons respond to.

Dan also has begun probing the function of the prefrontal cortex, the region of the brain responsible for more complex reasoning. The fine-scale circuitry of the prefrontal cortex has been largely unknown territory, but with her cell-labeling technique—adapted from Shi’s work—she is poised to explore at the level of individual neurons.

When Dan thinks about Shi’s seminar now, she pauses and her voice drops just a bit. “It was a pretty fateful moment. If I had missed that seminar, we would not have thought about the sister-neuron project at all. It really opened up a big line of research for us.”

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