A new Salk study is the first to closely follow the development of new neurons in the adult brain, giving insight into neurodevelopmental disorders such as autism and schizophrenia. By genetically engineering new neurons to fluoresce green, researchers were able to see when the new cells grew and branched surrounded by other cell nuclei (blue) in the brain. Credit: Salk Institute
A new study is first to closely follow development of new neurons in the adult brain, giving potential new insight into neurodevelopmental disorders such as autism and schizophrenia. New brain cells began with a period of overgrowth, sending out a plethora of neuronal branches, before the brain pruned back the connections. “We were surprised by the extent of the pruning we saw,” says Prof. Rusty Gage.
While most of the brain’s billions of cells are formed before birth, Gage and others previously showed that in a few select areas of the mammalian brain, stem cells develop into new neurons during adulthood. In the new study, Gage’s group focused on cells in the dentate gyrus, responsible for the formation of new memories. A new microscopy technique was used to observe new cells being formed in the dentate gyrus of adult mice.
“This is the first time we’ve been able to image dentate neurons growing in a living animal,” says Tiago Gonçalves, Gage lab . They followed on a daily basis the growth of neurons over several weeks. When animal were housed in environments with lots of stimuli, running wheels, plastic tubes, and domes, the new cells grew quickly, sending out dozens of dendrites which receive electrical signals from surrounding neurons. When kept in empty housing, the new neurons grew slightly slower and sent out, on average, a few less dendrites. But, in both cases, the dendrites of the new cells began to be pruned back.
“What was really surprising was that the cells that initially grew faster and became bigger were pruned back so that, in the end, they resembled all the other cells,” says Gonçalves. He and his colleagues went on to show that changing signaling pathways could mimic some of the effects of the complex environment — cells grew more initially, but also pruned back earlier.
The researchers suspect that the more dendrites a neuron starts with, the more flexibility it has to prune back exactly the right branches. “The results suggest that there is significant biological pressure to maintain or retain the dendrite tree of these neurons,” says Gage. Defects in the dendrites of neurons have been linked to numerous brain disorders including schizophrenia, Alzheimer’s, epilepsy and autism. Charting how the brain shapes these branches-both during embryonic development and in adulthood-may be the key to understanding mental health.
“This also has big repercussions for regenerative medicine,” says Gonçalves. “Could we replace cells in this area of the brain with new stem cells and would they develop in the same way? We don’t know yet.” http://www.salk.edu/news-release/adult-brain-prunes-branched-connections-of-new-neurons/
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