Neuroscientists find brain stem cells that may be responsible for higher functions, bigger brains

ScienceDaily (Aug. 7, 2012) Scientists from The Scripps Research Institute have identified a new stem cell population that may be responsible for giving birth to the neurons responsible for higher thinking. The finding also paves the way for scientists to produce these neurons in culture -- a first step in developing better treatments for cognitive disorders, such as schizophrenia and autism, which result from disrupted connections among these brain cells.

Published in the August 10, 2012 issue of the journal Science, the new research reveals how neurons in the uppermost layers of the cerebral cortex form during embryonic brain development.

"The cerebral cortex is the seat of higher brain function, where information gets integrated and where we form memories and consciousness," said the study's senior author Ulrich Mueller, a professor and director of the Dorris Neuroscience Center at Scripps Research. "If we want to understand who we are, we need to understand this area where everything comes together and forms our impression of the world."

In the new study, Mueller's team identified a neural stem cell in mice that specifically gives rise to the neurons that make up the upper layers of the cerebral cortex. Previously, it was thought that all cortical neurons -- those making up both the lower and upper layers -- came from the same type of stem cell, called a radial glial cell, or RGC. A neuron's fate was thought to be determined by the timing of its birth date. The Scripps Research team, however, showed that there is a distinct stem cell progenitor that gives rise to upper layer neurons, regardless of birth date or place.

"Advanced functions like consciousness, thought, and creativity require a lot of different neuronal cell types and a central question has been how all this diversity is produced in the cortex," said Santos Franco, a senior research associate in Mueller's laboratory and first author of the paper. "Our study shows this diversity already exists in the progenitor cells."

Peeling Back the Onion Layers

In mammals, the cortex is made up of six distinct anatomic layers holding different types of excitatory neurons. They are not the uniform layers of a cake, but rather, they are more like the layers wrapped around an onion. The smaller lower layers, on the inside, host neurons that connect to the brain stem and spinal cord to help regulate essential functions such as breathing and movement. The larger upper layers, closer to the outer surface of the brain, contain neurons that integrate information coming in from the senses and connect across the two halves of the brain.

The upper layers are a "relatively young invention," evolutionarily speaking, having been greatly expanded during primate evolution, said Mueller. They give humans in particular the unique abilities to think abstractly, plan for the future and problem-solve.

For the last two decades, scientists have believed that the fate of cerebral cortex neurons was determined by their birth date because each layer is formed in a time-dependent manner. The lower layer neurons form in the center of the "ball" first, and then the cells that will become the upper layers form last, migrating through the lower layers.

"So the model was that there is a stem cell in the center of the ball that generates the different types of neurons in successive waves," said Mueller. "What we now show is that there are at least two different populations of RGCs and potentially more."

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Neuroscientists find brain stem cells that may be responsible for higher functions, bigger brains