PLASTIC PHASE: Johns Hopkins researchers have identified a two-week window in the young life of a new neuron in the adult brain when it is as adaptable as a brain cell in a newborn baby. Image: © ISTOCKPHOTO/SEBASTIAN KAULITZKI
Researchers have identified a "critical period" during which new nerve cells in adult brains have the same capacity to learn as those in developing brains. The finding in mice, reported in this week's Neuron, provides the promise of therapies that may one day limit or perhaps even reverse the damage of neurodegenerative diseases such as multiple sclerosis and Parkinson's.
Scientists first observed neurogenesis—the creation of new neurons in the adult brain—in animal brains in the 1960s but did not find evidence of it in humans until the late 1990s, says senior study author Hongjun Song, an assistant professor of neurology at the Johns Hopkins University School of Medicine in Baltimore.
Song says he and his colleagues set out to determine whether the young cells differed from older ones—and, if so, how much and at what stage of development.
Using a retrovirus that targets dividing, or reproducing, cells, the team tracked new neurons in the hippocampus (a midbrain structure involved with learning and memory) from their births to their deaths. The scientists could determine the behavior of cells by measuring their electrophysiological activity during different phases. "In young animals, cells are very active, very plastic, and they can change their properties readily," he says. "This whole process [also] happens in the environment of adult circuitry."
The team found that there is a two-week window, or critical period, about a month after these new cells hatch during which they act like the neurons of a newborn baby. The researchers cued the new cells with a pattern of electrical activation that mimics the sequence that takes place in the brain of a mouse as it learns about a special spot (such as a corner in its cage where it may receive food or a shock). During this time, the cell synapses (connections that allow neurons to communicate with each other) that are artificially stimulated become stronger.
This strengthening, known as long-term potentiation, results in more efficient information transmission between cells, and is thought to prime them to learn. "For the young cells, it's much easier to be potentiated, but, also, once they are potentiated, the amount of potentiation is much bigger than with brand-new cells," Song says. "What this does is allow [these young cells] to fine-tune their connections."
"From these data it seems that for high levels of plasticity what matters is the age of the single neuron and not the age of the brain in which the new neuron becomes incorporated," says Tommaso Pizzorusso, a neurobiologist at the Institute of Neuroscience of the National Research Council in Pisa, Italy. "Unfortunately, adult neurogenesis is limited to very specific structures of the brain and, therefore, the remainder of the brain is left with reduced levels of plasticity typical of 'old' cells."
Song believes that the new findings may open the door to stem cell–based therapies for diseases like multiple sclerosis, Parkinson's and Alzheimer's in which "mature neurons have died and all those fine connections are gone." He says such treatments could involve injecting young nerve cells, in the regions where they are not already continuously being produced, to upgrade flawed existing neural circuitry. "Introducing young neurons," he says, "can make the older circuitry more plastic and adapt to new conditions."