Recent evidence suggesting that antidepressants may act by triggering the birth of new neurons in the adult hippocampus,* the brain's memory hub, has heightened interest in such adult neurogenesis and raised the question: Could new neurons also be sprouting up in the parts of the adult brain involved in the thinking and mood disturbances of depression and anxiety?
Now, scientists at the National Institute of Health's (NIH) National Institute of Mental Health (NIMH) have found newly born neurons that communicate via the chemical messenger GABA (gamma-aminobutyric acid) in adult rat cortex, seat of higher order "executive" functions, and in the striatum, site of habits, reward and motor skill learning. In the cortex, the new neurons appear to arise from previously unknown precursor cells native to the area, rather than from cells migrating in from another area. NIMH's Drs. Heather Cameron, Alexandre Dayer, and colleagues, report on their findings in the January 31, 2005 Journal of Cell Biology.
Their discovery adds to the scientific debate over adult neurogenesis, which has potential implications for understanding a variety of brain disorders, possibly including Alzheimer's and schizophrenia. While most researchers agree that new neurons are generated in the adult hippocampus and olfactory bulb, the existence of adult neurogenesis in other brain regions remains controversial.
The NIMH team used many more markers than previous studies to track newborn neurons as they matured and to identify the type of neurotransmitters they secreted. The markers exploited antibody affinities for specific proteins to tag particular cell types with telltale color codes, visible on brain slices under fluorescence with a laser-powered microscope.
The researchers found that the cortex and striatum were giving birth to new, widely scattered small cells, called interneurons, that make and secrete GABA, a neurotransmitter that dampens neuronal activity. The new interneurons closely resembled those seen in the hippocampus and olfactory bulb and seemed to arise at similar rates. Interneurons are thought to play a role in regulating larger types of neurons that make long-distance connections between brain regions and predominate in these areas.
The NIMH team was surprised to find that the new cortex interneurons appeared to arise from a previously unknown class of local precursor cells rather than from cells that migrate into the area from the subventricular zone, where other neurons – including those seen in the striatum and olfactory bulb – originate during adulthood. However, during development, both the cortex and striatum precursors likely stem from common ancestor cells that somehow retain their ability to divide and generate new GABA interneurons, propose the researchers.
"Since antidepressants increase neurogenesis in the adult hippocampus, they might have similar effects in the cortex, the region probably responsible for mood dysregulation in depression," suggested Cameron. "But answers to such questions about regulation and possible functions of the new neurons must await results of future studies."
Also participating the project were Kathryn Cleaver and Thamara Abouantoun of the NIMH Unit on Neuroplasticity. Dr. Dayer's work was supported by the Swiss National Fund.
NIMH is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
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