Why the Adult Brain Keeps Making New Neurons

The short answer is that, at least in one region of the brain, the hippocampus, most of the data indicate that neurons do keep forming in adulthood, although how many, and how much they matter, remains one of the open debates in neuroscience.

To see why the question carries so much weight, we have to start with the person who closed it for half a century: Santiago Ramón y Cajal.

Cajal’s dogma

Cajal, who won the Nobel Prize in 1906, spent years studying what happens when a nerve or a pathway in the central nervous system is damaged. He collected that work in Estudios sobre la degeneración y regeneración del sistema nervioso (Madrid, 1913-1914), and his conclusion was categorical: in the adult nerve centers, the pathways are something fixed, ended and immutable.

In the 1928 English translation the line became famous: “everything may die, nothing may be regenerated.” Cajal added that it was for the science of the future to change, if possible, this harsh decree.

That principle became the no-regeneration dogma, and for decades neuroscience assumed that the adult brain could only lose neurons.

There is an important nuance: Cajal did not see the brain as something inert. In his Croonian Lecture to the Royal Society (1894) he had already compared it to a garden of trees that:

“in response to intelligent cultivation, can increase the number of their branches, spread their roots over a wider area, and produce ever more varied and exquisite flowers and fruits.”

But he was referring to new connections between existing neurons, the basis of what we now call neuroplasticity, not to new neurons. Plasticity, yes; neurogenesis, no.

The first cracks: Altman and the rats

In 1965, Joseph Altman and Gopal Das published evidence in the Journal of Comparative Neurology that in the hippocampus of rats, after birth, new cells kept appearing and turning into neurons. They used radioactive thymidine, a marker that is incorporated into the DNA of dividing cells.

The finding clashed with the dogma and took decades to be accepted. What finally changed the picture was the demonstration in humans.

Eriksson, 1998: the first evidence in humans

Confirming neurogenesis in people is much harder than in animals: identifying a newly formed neuron requires labeling cells at the moment they divide, something that cannot be done in a healthy human brain purely for research.

In November 1998, Peter Eriksson, Fred Gage and their team found a way. They analyzed brain tissue, after death, from cancer patients who had received a marker of dividing cells (bromodeoxyuridine, BrdU) during their lifetime as part of their oncology follow-up. In the dentate gyrus of the hippocampus there were labeled cells that had become neurons: they had formed in adulthood.

How many neurons: the carbon-14 method

Kirsty Spalding, Jonas Frisén and their team (2013) looked for another way to measure. The atmospheric nuclear tests of the 1950s and 1960s sent the amount of carbon-14 in the air soaring, and that carbon was recorded in the DNA of cells forming at each point in time. By measuring the carbon-14 in hippocampal neurons of deceased people, it is possible to estimate when each cell was born.

Their result: about a third of the neurons in the dentate gyrus are renewed over the course of life, with roughly 700 new neurons a day in each hippocampus in adults and a modest decline with age.

Where new neurons are born

Hippocampal neurogenesis takes place in the dentate gyrus. There, precursor or stem cells divide and give rise to cells that migrate a short distance, differentiate into neurons and form connections with existing ones.

In rodents, a good share of these neurons do not survive beyond the first few weeks; those that do become integrated into the circuits. The fact that it is the hippocampus, a key region for memory, that keeps this capacity opened a line of research that is still active.

The 2018 debate

In March 2018, Shawn Sorrells, Arturo Álvarez-Buylla and their team published a study in Nature using brain samples from children and adults: neuron formation dropped sharply in childhood, and they did not detect it in adults.

A month later, Maura Boldrini and her team published the opposite result in Cell Stem Cell: in 28 people aged 14 to 79 who had died suddenly, they found thousands of immature neurons in the hippocampus, in similar numbers in young and older people.

In 2019, María Llorens-Martín’s group at the Severo Ochoa Center for Molecular Biology in Madrid analyzed brains processed under tightly controlled conditions, with little time before the tissue was fixed. They found thousands of immature neurons in the dentate gyrus of healthy people up to their nineties, and a marked drop in patients with Alzheimer’s disease.

A large group of specialists led by Gerd Kempermann (2018) summed up the state of the question: most of the evidence supports the existence of hippocampal neurogenesis in adult humans, but its scale and function are still unclear, and results depend heavily on how the tissue is obtained and processed.

What helps this process, and what slows it down

Almost everything known about what promotes neurogenesis comes from laboratory animals:

• Exploring stimulus-rich environments increases the formation of new neurons and their chances of survival.
• Sustained stress and a lack of stimulation reduce both.

This finding ties in with why stress blocks memory: in rodents, chronic stress not only makes it harder to retrieve what has been learned, it also slows the formation of neurons in the hippocampus.

Learning and making neurons: a two-way circuit

Elizabeth Gould and her team (1999) showed in rats that the relationship also works in reverse: learning tasks that depend on the hippocampus increased the survival of new neurons, while learning tasks that do not depend on it had no such effect.

In rats, then, taking in new information seems to feed back into the process. Carrying this over to humans is harder: neurogenesis cannot be measured in a living person, and no study has shown that studying more produces more neurons. The cautious takeaway is the general, well-documented idea that the adult brain retains a capacity for change.

How deeply you engage with what you’re learning, more than the hours you put in, is exactly what our deep vs. surface learning quiz measures.

What we know and what we don’t

• We know that the adult mammalian brain forms new neurons in the hippocampus, and most studies in humans point the same way.
• We know that Cajal was right to describe the plasticity of connections and wrong to consider the formation of neurons closed.
• We don’t know precisely how many new neurons an adult human forms, how much they contribute to memory, or whether the factors that promote them in rats have a meaningful effect in people.

Sources

• Altman, J., & Das, G. D. (1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. Journal of Comparative Neurology, 124(3), 319-335. https://doi.org/10.1002/cne.901240303
• Boldrini, M., Fulmore, C. A., Tartt, A. N., Simeon, L. R., Pavlova, I., Poposka, V., et al. (2018). Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell, 22(4), 589-599. https://doi.org/10.1016/j.stem.2018.03.015
• Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4(11), 1313-1317. https://doi.org/10.1038/3305
• Gould, E., Beylin, A., Tanapat, P., Reeves, A., & Shors, T. J. (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nature Neuroscience, 2(3), 260-265.
• Kempermann, G., Gage, F. H., Aigner, L., Song, H., Curtis, M. A., Thuret, S., et al. (2018). Human adult neurogenesis: Evidence and remaining questions. Cell Stem Cell, 23(1), 25-30. https://doi.org/10.1016/j.stem.2018.04.004
• Moreno-Jiménez, E. P., Flor-García, M., Terreros-Roncal, J., Rábano, A., Cafini, F., Pallas-Bazarra, N., Ávila, J., & Llorens-Martín, M. (2019). Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nature Medicine, 25(4), 554-560. https://doi.org/10.1038/s41591-019-0375-9
• Ramón y Cajal, S. (1894). The Croonian Lecture: La fine structure des centres nerveux. Proceedings of the Royal Society of London, 55.
• Ramón y Cajal, S. (1913-1914). Estudios sobre la degeneración y regeneración del sistema nervioso. Moya. English translation: Degeneration and Regeneration of the Nervous System (R. M. May, Trans.). Oxford University Press, 1928.
• Sorrells, S. F., Paredes, M. F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K. W., et al. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature, 555(7696), 377-381. https://doi.org/10.1038/nature25975
• Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., et al. (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell, 153(6), 1219-1227. https://doi.org/10.1016/j.cell.2013.05.002