For more than six decades, neuroscientists have wrestled with a fundamental question about the human brain: Do adults continue to make new neurons, or are we born with all the brain cells we’ll ever have? This has been much more challenging to answer than meets the eye.

Now, researchers at Sweden’s Karolinska Institutet say they’ve found the clearest answer yet. They report the discovery of dividing neural progenitor cells — essentially the precursors to new neurons — in the brains of humans ranging in age from infancy to 78 years old.

“We nailed down active neurogenesis in the adult human brain,” Marta Paterlini, co-lead author of the study, told PopSci.

The research offers the most direct evidence so far that neurogenesis—the process of generating new neurons—continues in the adult human hippocampus, a region involved in memory, learning, and emotion.

The Missing Link in the Neurogenesis Debate

This study addresses a major gap that had kept the field divided for decades. Earlier work hinted that new neurons might be forming in adults, but without clear evidence of the cells that actually give rise to them (the neural progenitors), many scientists remained skeptical.

“Now we have very strong evidence that the whole process is there in humans, from the precursor cells to the immature neurons,” Gerd Kempermann, a neurobiologist not involved in the study, told Scientific American.

To find these elusive cells, the Karolinska team analyzed brain tissue samples from 25 donors. Their ages ranged from newborn to late adulthood. To pinpoint cell activity in a subregion of the hippocampus called the dentate gyrus, the researchers used a battery of cutting-edge techniques, including single-nucleus RNA sequencing, flow cytometry, and two gene-mapping methods (RNAscope and Xenium).

The team also used machine learning algorithms to sift through genetic signatures in more than 100,000 cells. Ultimately, they identified 354 cells that were in various stages of developing into neurons, dozens of which were found in fully grown adults.

A Brain That Grows

What makes this study stand out isn’t just the identification of young neurons, but the discovery of the cells that made them.

“We have now been able to identify these cells of origin, which confirms that there is an ongoing formation of neurons in the hippocampus of the adult brain,” said Jonas Frisén, senior author and stem cell biologist at Karolinska.

Some adults had many of these progenitor cells. Others had few, or none. Interestingly, there was no clear link between age or known illness and the presence of these cells. One 58-year-old donor had the highest number of young neurons and no recorded brain disease.

While animal studies have long confirmed adult neurogenesis in rodents, pigs, monkeys, and birds, its presence in humans has remained a hotly contested issue. The human brain’s huge complexity led some experts to argue that adding new neurons might disrupt rather than enhance brain function.

That’s part of why confirming the existence of these cells has been so difficult. Human brain tissue is incredibly hard to study, usually available only after death or during surgery. And standard imaging techniques can’t peer deep enough to spot dividing cells in action.

This study helps overcome that challenge by combining advanced sequencing and imaging techniques with artificial intelligence, allowing researchers to draw high-confidence conclusions from sparse and precious brain samples.

Uncertainty About Neurons

Still, not all experts are convinced. Shawn Sorrells, a neuroscientist at the University of Pittsburgh, was excited when he first heard about the study. But he now questions whether the researchers truly found neural stem cells, or possibly misidentified other cell types.

“The most likely conclusion is that the cells they are looking for are rare or nonexistent in most people,” Sorrells told PopSci. “The other possibility is that the cells they claim are adult neural stem cells are associated with a disease process in these individuals or some other cell type altogether.”

He points out that glial cells, supporting cells in the brain, do divide in adulthood, and could be mistaken for neuron-producing cells. Others, like Mercedes Paredes at UCSF, call the research a “good starting point” but say more work is needed to confirm the findings and understand the cells’ roles.

Even the study’s own authors acknowledge that these cells appear to be rare. In their sample, fewer than half of adult brains showed signs of neurogenesis. However, the absence of developing brain cells in some samples may be primarily due to how the brain tissue samples were preserved after a person died. Brain tissue has to be preserved within a few hours after death. And specific chemicals used to preserve the tissue, or the proteins that identify newly developing cells will be destroyed.

Implications for the Aging Brain

If adult neurogenesis is real (and beneficial), it could open new doors for treating neurodegenerative and psychiatric conditions. In animal studies, reduced neurogenesis has been linked to disorders like Alzheimer’s disease and depression. A previous 2019 study published in Nature Medicine reached similar conclusions, finding adult hippocampal neurogenesis is “abundant”.

Some of the study’s authors hope their findings might one day be applied in regenerative medicine, potentially helping the brain heal after trauma or disease.

“Our research may also have implications for the development of regenerative treatments that stimulate neurogenesis in neurodegenerative and psychiatric disorders,” said Frisén.

“The lab is working on regenerative medicine,” said Paterlini. “So we will keep going on this.”

Now that scientists have found the cells capable of forming new neurons in adult humans, the next challenge is understanding what triggers their growth — or their absence in so many other people. It’s a question with implications far beyond memory and learning. It touches on who we are, and how we change over time.

As Kempermann put it:

“We can now concentrate on the question: How do these cells in the human contribute to brain function?”

The findings were published in Science.