New Brain Cells: Torrent, or Trickle?

An important paper just out asks, Could adult hippocampal neurogenesis be relevant for human behavior?

Neuroscientists, and the media, are very excited by hippocampal neurogenesis - the ongoing creation of new neurons in an area called the dentate gyrus of the hippocampus. This is because it was thought, for a long time, that no new neurons were created in the adult brain. It turned out that this was wrong.

There's lots of exciting suggestive evidence that the process is involved in learning and memory, responses to stress, depression, and the action of antidepressants, to name just a few, although this is controversial.

However, there's a big question which has rarely been considered: how much neurogenesis are we talking about? Are there enough new cells that it would be realistic for them to be doing important stuff, or is it just a little trickle?

The most common source of skepticism toward a functional role for adult neurogenesis is the perception that too few new neurons are added in adulthood to have a significant impact. Interestingly, this concern, while valid, is usually raised informally and rarely in the scientific literature. Very few studies have addressed this issue...

The new paper reviews the evidence. Firstly, they point out that in the hippocampus, there's a group of cells called dentate gyrus granule cells which are unusual in that activity in just a few of these cells can have big downstream consequences. And these are the cells that new born neurons turn into.

Each granule cell contacts only 10–15 CA3 pyramidal cells...a single granule cell is able to trigger firing in downstream CA3 targets...Because of this “detonator” action...a single granule neuron can potentially have a large impact despite representing only a tiny fraction of the population.

So new cells may play an important role. But exactly how many are there? They re-analyze data from their own lab in rats, and, making a few assumptions, arrive at the following rough estimate: in 3 month old rats, there are 650k "young" cells less than 8 weeks old; even in 2 year old rats (ancient, for a rat) there are 50k.

This is enough to have a big impact downstream:

Since there are approximately 500,000 CA3 pyramidal cells, and each granule cell contacts 11–15 pyramidal cells, this suggests that even in the oldest animals, each CA3 pyramidal cell could receive a direct contact from a young granule cell

That's all in rats, though. What about humans? It's hard to tell. The problem is that the best way to assess the rate of neurogenesis is to inject a drug called BrdU and then study the brain post-mortem. Unfortunately, this drug can cause cancer so you can't just give it to people for the purposes of science. The only time it's used in humans is (ironically) to help detect cancer.

However, one study did manage to look at BrdU staining in the hippocampus, using people who'd been injected with BrdU for cancer (not brain cancer) and then died. This study found, the authors say, rates of neurogeneis at least as high as in rats, considering the low dose of BrdU, the fact that the patients were old, and stressed (by having cancer).

They admit that this is just one study, and comparing doses between rats and humans is inexact. They nonetheless conclude:

Are these numbers potentially sufficient to exert a functional impact in humans? We feel that the answer to this question is an overwhelming "yes".

Snyder JS, & Cameron HA (2011). Could adult hippocampal neurogenesis be relevant for human behavior? Behavioural brain research PMID: 21736900