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Working on the “ultimate machine” drives career in neuroscience

Steve Noctor Stephen Noctor.

As an undergraduate student at Rutgers University in the 1980s, Stephen C. Noctor had to take a course called ‘Conditioning and Learning’ to get his bachelor’s degree. Part of the charm was the enthusiasm of the professor, Charles F. Flaherty, an authority on learning and memory who died of cancer in 2004. But the subject matter, which included instruction in the nuts and bolts of brain anatomy and brain chemistry, was the real draw.

“It was where I first learned about brain cells and neurotransmitters,” recalls Noctor, a 43-year-old neuroscientist who joined the UC Davis M.I.N.D. Institute in July. “It completely turned me on.”

Noctor ended up volunteering in Flaherty’s laboratory for two years while he completed his undergraduate studies, a time during which he “learned how laboratory science was done.” Then in graduate school, at the Uniformed Services University of the Health Sciences in Bethesda, he supplemented his neuroscience training with medical courses.

From a young age Noctor had shown signs of a scientific turn of mind. “I liked taking things apart to see how they worked,” relates Noctor, who grew up in New Jersey. “I started with clocks.”

So it shouldn’t be surprising that Noctor, who earned his doctorate in neuroscience in 1998 and then did a five year post-doctoral stint at Columbia University in New York, would become an expert in the inner workings of what might be thought of as the ultimate machine – the human brain.

Noctor’s area of expertise has to do with the explosion in brain cell production that takes place over a relatively short period of time during development of the cerebral cortex. In particular, he investigates the factors that control proliferation of the precursor cells that produce cortical neurons and glia, and how cortical cells migrate to reach their appropriate position.

Given their tiny size – on the order of 5 microns – the distances these cells travel within the developing brain are vast. “It’s the equivalent of climbing the Empire State Building four times,” Noctor said. And the newborn cells do climb – on the scaffolding provided by a type of neuronal precursor cell called radial glial cells that Noctor has identified through his research.

“We used to think the newborn neurons just went from point A to point B,” he says. “But we now know that there are important staging areas where the migrating cells stop and wait to receive information about what to do next.”

Complex signaling pathways regulate this extraordinary process of cell production and migration. And, not surprisingly, a number of neurological disorders result when things go wrong.

Sometimes cells go to the initial staging area and, for unclear reasons, fail to move further. Abnormal cell migration can lead to conditions like double cortex syndrome, a rare disorder which can cause mental retardation and epilepsy and is due to a misplaced layer of nerves that develop under the cortex. Lissencephaly, a disease characterized by a lack of brain folding that leaves its victims severely compromised, occurs when too few cells are produced. Noctor said autism may be caused by deficits in the proliferation process.

Noctor is hopeful that the great strides that have been made in brain research in recent years, advances that he said are due to the “molecular biology revolution” and breakthroughs in genetics, will eventually lead to treatments for such conditions.

“In the last 10 years, we’ve learned more about the brain than in the previous century,” Noctor says.

That’s not to say he and other neuroscientists don’t have a lot left to learn. “The brain is still a black box. There are so many questions that remain unanswered.”

Maybe that explains why Noctor seems just as excited about neuroscience today as he was when he took that undergraduate course at Rutgers back in the 1980s.

“Science is both my job and my hobby. It sounds geeky, but I spend most of my spare time in the lab.”