In the olfactory bulb, new neural stem cells learn to listen before they speak

Like a newborn learning from its parents, a neuron born of neural stem cells in the adult brain must take its cues from its elders if it hopes to mature and survive, according to new research headed by Charles A. Greer, Ph.D., professor of neurosurgery and neurobiology.

In findings published in the September 12, 2007, issue of The Journal of Neuroscience, Greer and Mary C. Whitman, an M.D./Ph.D. candidate in his lab, tracked the development of new neurons in a region of the brain called the olfactory bulb, which receives information about odors from the nose. It is one of the few regions in the adult brain that allows new neurons to be generated and integrated into existing neural circuits.

However, such assimilation is not easy. New brain cells destined for the olfactory bulb have to migrate vast distances from their birthplace, and half of these newborn neurons die between 15 and 45 days after being generated, presumably because they fail to integrate within the neural circuitry.

Greer and Whitman found that although the long, spindly arms of new neurons are present 10 days after being generated, they don’t form the connections that let them talk to other olfactory bulb neurons until three weeks after birth. Even then, it takes six to eight weeks for the cells to mature and achieve complete integration.

“New neurons are essentially taught to listen before they’re allowed to talk,” said Greer. He and Whitman found that fibers extending from older neurons located in higher centers of the brain first connect to short arms projecting from the base of new neurons about 10 days after generation. Whitman and Greer believe that these early synapses provide a conduit through which elder brain cells control the development, and ultimately the survival, of new neurons within existing brain circuitry. This ensures that the new lines of communication don’t garble pre-existing lines.

According to Greer, these findings have important implications for using adult neural stem cells to replace brain cells lost by trauma or neurodegeneration, such as in Parkinson’s disease. “To use stem cells in a transplant strategy, we’re going to have to understand the kinds of synapses new brain cells make as well as the kinds of synapses they receive from existing circuits. Our goal is to prevent these cells from being potentially disruptive by getting into the wrong synaptic circuit or by acting in a precocious way,” he said.