University of Pennsylvania: New evidence suggests human brain produces immature neurons throughout lifespan

There’s been a long-standing controversy about whether the mature human brain produces new immature neurons throughout its lifespan—what’s called “adult neurogenesis”—or whether the existing ones had to last throughout adulthood.

A team led by researchers at the Perelman School of Medicine has found that in the hippocampus, a key memory region of the brain, immature, plastic neurons are present in significant numbers throughout the human lifespan, findings they shared in the journal Nature. The discovery paves the way for the deeper study of adult neurogenesis and its roles in memory, mood, behavior, and brain disorders.

“Many mammals generate new neurons in their brains throughout their lifespans, which play a critical role in the brain’s plasticity, or ability to change and adapt over time,” says Hongjun Song, a Penn professor of neuroscience. “This ability to repair itself is especially important when the brain is damaged, which is what happens during a stroke or brain injury. This plasticity is also important for understanding diseases like Alzheimer’s, which affect a patient’s memory, among other functions.”

The existence of adult neurogenesis in humans has been debated for decades. For almost a century, neuroscientists assumed that once the mammalian brain matured, it generated no new neurons. Eventually, studies began to provide evidence of newly produced, immature neurons in the adult brain, in mice, humans, and other mammals, especially in the olfactory (smell) region, and in the hippocampus.

However, in the past few years, other studies have found no evidence of significant adult neurogenesis in the human hippocampus. It has been difficult for neuroscientists to settle the debate because they haven’t had an easy, sensitive, specific method for identifying newly produced, immature neurons in samples of adult human brain tissue.

Song, Guo-li Ming, a Penn professor of neuroscience, and their team overcame this challenge with the help of two powerful and relatively new tools. The first is single-nucleus RNA sequencing, which records essentially all gene activity in any individual cell. The second is machine learning, a type of artificial intelligence that, in this case, the researchers used to sift through enormous gene-activity datasets—for mice and humans—to learn the subtle differences between mature and immature hippocampal neurons.

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