For most of the 20th century, neuroscience operated on a principle that seemed self-evident: adult brains do not make new neurons. You are born with what you have. Neurons die throughout your life and are not replaced. This was treated as established fact, taught in medical schools, and used as a framework for understanding neurodegenerative diseases, aging, and cognitive decline.
Then, starting in the 1990s, researchers began finding evidence that this was wrong. New neurons appeared to be forming in adult brains, a process called adult neurogenesis. The hippocampus, the brain region most associated with memory formation, seemed to be an active site for new neuron production throughout adulthood. The implications for understanding depression, Alzheimer’s disease, and cognitive health were enormous.
And then, in 2018, another paper came out suggesting the first researchers were wrong. Adult neurogenesis in humans might not exist, or might be far more limited than thought. Then more papers disagreed with that paper. The debate has been running for six years and still has not fully resolved. Here is where it stands and why it matters.
How The Discovery Got Made (And Why It Was Controversial Immediately)
The modern neurogenesis debate started with work by Fred Gage and colleagues at the Salk Institute in 1998, demonstrating new neuron formation in the adult human hippocampus. The evidence came from postmortem brain samples from cancer patients who had been given BrdU, a marker that incorporates into dividing cells’ DNA. The hippocampal samples contained cells that had divided after the BrdU was administered, suggesting new neurons had formed during adulthood.
The finding challenged a century of conventional wisdom and was met with both excitement and skepticism. The methodological debate was immediate: how do you distinguish genuinely new neurons from neurons that had divided their DNA without becoming new cells? How do you handle the technical challenges of postmortem brain tissue preservation? Were the BrdU-labeled cells definitely neurons rather than other cell types?
The following two decades produced hundreds of studies, mostly in rodents and other animals, supporting robust adult neurogenesis in the hippocampus. Animal studies also connected neurogenesis to learning, depression, and stress response. Running, antidepressants, and enriched environments all appeared to increase hippocampal neurogenesis in rodents. The idea that you could promote your brain’s neuroplasticity through behavior became a widely cited framing in popular science.
The 2018 Study That Complicated Everything
In 2018, a Nature paper from Arturo Alvarez-Buylla’s lab at UCSF analyzed human hippocampal tissue with updated techniques and found no evidence of new neurons in adults. The team used more sophisticated cell markers and fresher tissue samples than earlier studies and concluded that neurogenesis, if it happened at all, was extremely rare in adult humans and dropped sharply after early childhood.
This was a serious challenge because the new study used better methods and came from a credible lab. But it also immediately faced criticism. Tissue fixation and preparation methods significantly affect the appearance of neurons. Newer cells, which might represent recent neurogenesis, are actually harder to preserve intact, meaning studies using better-preserved tissue might paradoxically find fewer new neurons. The absence of evidence in a preservation-sensitive system might not be evidence of absence.
A 2019 rebuttal study from a different lab, using techniques specifically optimized to detect immature neurons in fresh tissue, found abundant new neurons in adults up to age 87. A 2023 meta-analysis found that when controlling for tissue quality and detection methods, the positive studies were significantly more methodologically consistent than the negative ones.
What The Current Evidence Actually Supports
Researchers who have reviewed the evidence most carefully generally land in a nuanced position: adult human neurogenesis almost certainly happens, but is more limited, more variable, and more difficult to detect than rodent studies suggested. The hippocampus is the most likely site. The number of new neurons produced appears to decline with age but may not go to zero.
Several findings have remained relatively consistent across studies. Carbon-14 dating of neurons (using atmospheric radiocarbon levels from nuclear weapons testing as a timestamp) supports a slow turnover of certain neurons in the adult hippocampus. Single-cell RNA sequencing has identified cell populations in the adult human brain that look like immature neurons at intermediate stages of development. These two independent lines of evidence are harder to explain away than immunohistochemistry results, which are more sensitive to preparation artifacts.
The rodent models remain robust and are not in dispute. Mice and rats show clear, substantial adult neurogenesis. The biological mechanisms involved in cell survival and renewal appear to be conserved across species, but with significant differences in rate and extent. Human neurogenesis appears to be much slower and more restricted than in rodents, which is consistent with the pattern of brain development across mammals generally: longer-lived animals with larger brains tend to have less neural plasticity but more stable neural circuits.
Why The Stakes Are High
The neurogenesis debate has direct implications for several areas of medical research.
Depression research took significant interest in the neurogenesis hypothesis after animal studies showed that stress suppresses hippocampal neurogenesis and antidepressants promote it. If a similar mechanism operated in humans, it would explain both the hippocampal volume loss documented in chronic depression and why antidepressants take weeks to become effective (the timescale of neurogenesis). If adult neurogenesis is minimal in humans, this model needs revision.
Alzheimer’s disease research is connected through the hippocampus. Early Alzheimer’s specifically destroys hippocampal function. If neurogenesis contributes to hippocampal maintenance and repair, its absence or impairment could accelerate decline. Several research programs aimed at promoting neurogenesis as a therapeutic approach depend on the mechanism being real and meaningfully scalable.
The lesson from the mantis shrimp color vision revision applies here too: the corrected picture is more complicated than the original story but also more precise about what is and is not happening. The question is not simply “do adult brains make new neurons?” but “which brain regions, at what rate, in response to what stimuli, and with what functional consequences?”
What This Means For The Larger Understanding of Brain Plasticity
Even setting aside the neurogenesis debate, the picture of the adult brain has changed enormously in the past 30 years. Synaptic plasticity, the ability of existing connections to strengthen or weaken, is now understood to be far more robust and dynamic than classical neuroscience assumed. The brain’s structure continues to change throughout adulthood in response to experience, learning, and environment.
New neurons may or may not be forming at meaningful rates in adult humans. Existing neurons are definitely changing, growing, and reorganizing throughout adult life. The old “born with what you have” model was wrong in important ways even if neurogenesis turns out to be more limited than hoped.
The neurogenesis debate has also been a useful case study in how science handles methodological challenges in systems where ground truth is hard to establish. The field has improved its methods, developed more independent lines of evidence, and is slowly converging on a more nuanced answer than either the original “neurogenesis is everywhere” or the 2018 “neurogenesis does not exist in adults” position. That is what productive scientific controversy is supposed to look like.
Sources: Gage et al. (1998, original adult neurogenesis study, Nature Medicine), Alvarez-Buylla et al. (2018, “Human adult neurogenesis”, Nature), Boldrini et al. (2018 rebuttal, Cell Stem Cell), Moreno-Jimenez et al. (2019, immature neurons fresh tissue, Nature Medicine), Bhanu et al. (2023 meta-analysis on tissue quality and neurogenesis detection methods).
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