No new brain cells for you – settling the neurogenesis debate

The human neocortex – the brain’s control centre – is fantastically versatile and constantly processes a vast amount of information. Amazingly, it does this using the same set of neurons (nerve cells) that it retains from birth, never adding new cells to the mix.

You are not the person you used to be. Two weeks ago, the surface of your skin was covered with a completely different set of cells, which have since died and flaked off. Four month ago, you had a wholly different set of red blood cells. Since birth, your body has grown tremendously in size and much of it is constantly regenerating, replacing old cells with new ones.

But your brain is different. At birth, the part of your brain that controls your most human abilities – the neocortex – came fully equipped with 100 billion nerve cells, or neurons. These same neurons have lasted throughout the years and still power your thoughts today.

The big questionThe neocortex is the outer layer of the large bit.

The neocortex makes up most of the brain. Its relatively large size is unique to humans, and with good reason.

In addition to controlling our bodies, its collection of neurons house our most characteristic qualities – our experiences, and our powers of language, reasoning and creativity. For this reason, the development of these neurons has fascinated scientists for decades.

Throughout our lives, the neocortex needs to change at an incredible pace as we accrue new memories and skills. One of the most hotly contested questions in neuroscience is how it copes – does it constantly grow new neurons (a process called neurogenesis), or do we have the same set from birth?

Until now, the question has had no hard answers because of inaccurate and easily misinterpreted research techniques. A reported sighting of newly-made neurons in primate brains fanned the flames of debate but could not be confirmed. Clearly, a new breakthrough was needed. It came from the most unlikely of techniques.

Carbon-dating neurons

Carbon dating measures the levels of 14C, a radioactive form of carbon found in small background levels in the atmosphere. It is a useful technique for working out the age of ancient artefacts, but it’s only accurate to about 30 years and has limited use for studying living cells.

But Ratan Bhardwaj and colleagues at the Karolinska Institute, Stockholm, found a way to do this. They exploited the fact that during the Cold War, the world’s superpowers busied themselves by testing their new nuclear arsenals. In doing so, they unleashed large amounts of 14C into the atmosphere and from 1955, global levels doubled in eight years.

The Test Ban Treaty of 1963 put an end to both nuclear testing and the rising 14C levels, which fell exponentially in the following decades. Meanwhile, the high atmospheric levels of 14C were converted into carbon dioxide and taken in by plants. In this way, 14C worked its way up the food chain, and some of it made it into the bodies and neurons of people alive at the time.

Nuclear testing sent 14C levels skyrocketing. So, the levels of 14C in any neuron acts as a time stamp, directly reflecting the amount of 14C in the air at the time it was created. Because the atmospheric levels changed so much from year to year, the team could accurately work out the birthday of each cell.

Bhardwaj and his colleagues looked at the levels of 14C in the neurons of 7 people born between 1933 and 1973.

The results were unequivocal. For each person, the levels of 14C in their neurons matched the levels in the air when they were born – high in those born after nuclear testing, and low in those born before it. The team studied millions of neurons, across the four distinct parts of the neocortex. Not a single one was younger than the brain that carried it.

The final blow

Bhardwaj did another study to confirm his sensational result. He looked at the brains of cancer patients who were injected with a chemical called BrdU before they died. BrdU is a variant of one of the four bases that make up DNA and once injected, it gets incorporated into newly-created DNA. In this way, the presence of BrdU acts as a marker for newborn cells.

Again, the experiment left no room for doubt – in these patients, many different types of cell were labelled with BrdU, but not a single one of them was a neuron.

While Bhardwaj admits that the techniques have their limits, they are incredibly sensitive. Any new neurons missed by the two methods would account for under 1% of the neocortex’s collection, and would be very short-lived.

At most, the neocortex adds one new neuron every year for every 7000 existing ones. Their impact on the existing million-strong network would be insignificant.

At last, a clear answer

Bhardwaj’s elegant experiments finally bring the debate crashing down in favour of one side. It is clear that all 100 million neurons in our neocortex are produced during a strict developmental window while we are still inside the womb. We are then stuck with these cells for our entire lives.How does a static neural population cope with new information?

How can a static population of neurons be reconciled with a dynamic adaptable brain that is anything but static?

Without new neurons, the neocortex’s vaunted flexibility must come from changing connections between existing neurons, constantly rewiring our mental circuits in the face of new experiences and sensations.

When it comes to neurons, it’s not how many you have, it’s how you use them that counts.

Evolving stability

Fish, reptiles and birds renew their neurons throughout their lives, but further along the evolutionary tree, the situation looks more human. In primates and rodents, new neurons only appear in two parts of the brain – the olfactory bulb, which controls the sense of smell, and the hippocampus, a region associated with building short-term memories.

There is good evidence that new neurons are created in these same regions in humans. But in the neocortex, stability is the order of the day. Bhardwaj believes that mammals have evolved a stable neural network so that we can retain important information throughout our lives, such as our language skills.

Our mental network was forged through experience, but new neurons are naïve. Adding them into the mix would change the flow of currents through the existing system existing network, causing potential problems. Anyone who watched the England football team recently can appreciate the chaos that ensues when new players are unexpectedly thrust into a stable formation.

Preventing the development of new neurons may even have been a critical step in the evolution of human intelligence. It is deliciously ironic that rigidly fixing the number of neurons in our brain may have allowed us to become more mentally dynamic than any animal could ever hope to be.

More about neurogenesis:
Bats create spatial memories without making new brain cells

And more about neurons: 
Simple sponges provide clues to origin of nervous systems
Monkeys (and their neurons) are calculating statisticians
Non-coding DNA drove brain evolution by making nerve cells stickier
Maternal hormone shuts down babies’ brain cells during birth

Reference:  Bhardwaj, Curtis, Spalding, Buchholz, Fink, Bjork-Eriksson, Nordborg, Gage, Druid, Eriksson & Frisen. 2006. PNAS 103: 12564-12568.

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13 Responses

  1. Wow; that is fascinating, and pretty conclusive, it appears. It would be interesting to know if this applies to areas of brain damage as well.

  2. Yeah wouldn’t it? I’d actually planned to make this the first in a series of articles exploring the ramifications of this result, but they kept on getting subsumed by other stories. This definitely raises lots of other questions:

    - Why is it that the hippocampus and the olfactory bulb of all places produce new neurons?
    - Is it possible to regenerate new neurons for medical reasons, e.g. in people who have had massive strokes?
    - How exactly is new information coded in the existing neural network?
    - If intelligence and experience don’t relate to neuron number, what *do* they relate to? Brain density? Connectiveness? How well-insulated the neurons are?

    I could go on. Maybe I will :-)

  3. I think you should!

  4. Not conclusive at all:

    I will make three points-

    1. neurogenisis especially in the neo-cortex occurs mostly during developmental stages and slows during adulthood just like the dentate-gyrus of the hippocampus, olfactory bulb, and subventricular zones etc..

    2. the study took DYING CANCER PATIENTS – neurogenisis is impaired everywhere and no connclusive evidence.

    3. if you are a scientist then what you say is almost outrageous- remember A cornerstone of biology is that for every problem there is a good experimental system or task paradigm to exploit the answer. This was not one of them.

    David V
    New York University
    Center for Neural Science
    dhv204@nyu.edu
    web.mac.com/david.h.valenzuela

  5. I will make several points in return:

    1. The fact that the study was in dying cancer patients is irrelevant. It wasn’t looking for recent neural development, but development over each person’s lifetime. Read the article.

    2. The almost palpable feeling of elitism and arrogance in this post, particularly in the third point, is exactly the sort of nonsense that this blog was put together to address. Instead of the interesting and measured discussions that really ought to fuel modern science, all too many debates and conferences descend into intellectual pissing competitions because of the gung-ho, self-absorbed attitudes of those involved. You might like to have a look at other posts on this site for examples where scientists have disputed the results of the articles but in interesting, polite ways that, you know, actually made sense.

    3. I find it amusing that a man who works at the “Center for Neural Science” has not yet learned to spell neurogenesis.

  6. Thank You

  7. I’m by no means a scientist, but I would never take 1 or 2 studies as conclusive evidence. Also for the neurogenesis that is known to occur, we don’t fully know what causes it. I would like to know what kind of lives and professions these people they studied had. I would have a hunch that if neurogenesis can occur in higher areas of the brain, that it would still take a lot of external stimulus; and not likely to be the same in any two people.

  8. Kyle, it’s a fair point, but one of the major strengths of this study is that they looked at a massive sample of neurons and clearly established the probability of having missed something.

    As I wrote: “While Bhardwaj admits that the techniques have their limits, they are incredibly sensitive. Any new neurons missed by the two methods would account for under 1% of the neocortex’s collection, and would be very short-lived.”

  9. [...] No new brain cells for you – settling the neurogenesis debate [...]

  10. There seems to be a ton more articles that show the opposite of your study on the net. Cells seem to be moved to whatever part of the brain needs repaired and this process was observed in each study I have read. Cells produced in the hippocampus travel long distances to the cerebral cortex and this was observed in several studies, all but this one as a matter of fact.

    Degenerative diseases seem to be caused by a decrease in this process, but supplements like Alpha Lipoic Acid prevents Alzeimers and Dementia and can even reverse these conditions by protecting the brain from oxidative stress and free radicals. After reading the majority of brain cell regeneration studies, it is likely that this protection allows the brain to regenerate cells and function normally again. There is tons of research being done on this now and your article, opinion and studies are very out of place with today’s information and research. If the brain didn’t regenerate, these studies to find out more wouldn’t be happening.

  11. OK firstly, it’s not *my* study – Not Exactly Rocket Science is essentially about news. I report new research, and all science is open to reassessment with new evidence.

    I’d love to see the studies that you mention. References?

  12. very interesting, if they can repair the brains of the mentally ill who know’s what else we can accomplish

  13. What is lacking in the study, unfortunately, is a positive control. I can not understand why the hippocampus was not included as a positive control for a brain region where adult-generated neurons are added.

    This would add substantial strengt to the study, and it is strage that this was requested by reviewers.

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