Why is there little neurogenesis in the brain?

For mammals, there are only two spots in the adult brain that support ongoing neurogenesis, or the development of new neurons: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. There also appears to be an emerging third neurogenic spot in the hypothalamus that participates in metabolism, but in general, the point remains: You won’t find many newborn neurons in the mature brain.

From a neural injury standpoint, it seems odd that there isn’t a lot of neurogenesis going on. If more pools of neural stem cells exist, wouldn’t that give the brain more opportunities to regenerate damaged or dead neurons? Indeed, a wider distribution of neural stem cells in the adult brain of zebrafish might explain why zebrafish are much better at neural regeneration than humans.

Here is what we have to remember. Adult neurogenesis is an extremely complex process. In general terms, you are taking what is happening during early development and recapitulating these events within a mature brain when adult neurogenesis occurs.

However, there is one major difference: The mature brain is not an environment that is permissive for neural development. For instance, as a neuron develops during its early stages, guidance cues allow the axon — “the arm” of the neuron — to reach its target. For the majority of the mature brain, these axon guidance cues are gone. Without such cues, neurons will have a challenging time reaching their targets. Such an inhibitory environment across most of the brain makes it hard to have widespread adult neurogenesis, except for in specialized niches that still seem to retain some sort of guidance mechanisms for the development of adult-born neurons.

Another factor that contributes to such an environment that is “hostile” to de novo neural development is that much of the brain has already been wired at an adult stage. Imaging trying to drive in busy traffic. There is already so much wiring going on that if new neurons are born and try to establish connections with pre-existing neural circuitries, there will be a conflict between what is already there and what is new.

In other words, the mature brain only has so much space that can accommodate new neurons. Computational modeling studies therefore suggest that the addition of new neurons during adulthood will inevitably disrupt the neural connections that already exist. This could be both good and bad. If such a process is regulated, as in the case of normal brain functioning, such deletions of old circuits might be beneficial in helping to replace old and decrepit information that the brain no longer needs with new and more useful information.

Too much neurogenesis, however, could significantly rewire neural networks, destroying information and perhaps even making us more susceptible to diseases. For instance, excessive adult neurogenesis has been implicated in conditions such as epilepsy. Blocking neurogenesis in an animal model of epilepsy reduced cognitive decline and seizure frequency. Given all the odds against adult neurogenesis, it is quite astonishing that the adult brain still manages to retain ongoing neurogenesis in small regions. What is therefore so special about these neural circuits that require the brain to go through all those efforts to make new neurons? There are several speculations, but this discussion will be saved for another day.