neuroDEVELOPMENTS

Adult Neurogenesis: Now you see it, now you don’t?

To build the cerebral cortex, a chain of events generates new neurons. Radial glial cells divide to produce intermediate neural progenitor cells, which in turn divide to produce neurons. Once these migrate to their destination, they mature into excitatory or inhibitory neurons. These neurogenic processes largely halt postnatally, seemingly mothballed for the duration.

Or are they? In the last three decades, researchers have repeatedly reported ongoing neurogenesis in adult mice and other mammals, particularly in the hippocampus, a region critical for learning and memory. Compared to the six-layered neocortex where excitatory neurons are generated on a tight schedule during fetal life, the hippocampus is part of an ancient, perhaps more laconic cortical system. Relative to the iconic, precise prenatal timing of neurogenic commitment in the neocortex, neurogenesis in the dentate (“tooth-shaped”) region of the hippocampus is delayed and prolonged. In mice, after an early initial commitment to the hippocampal fate, dentate granule neuron precursors initially generate the neonatal dentate gyrus and continue to produce granule cells in the young postnatal brain. As animals such as mice mature, neurogenesis wanes, yet continues into adulthood, long after the birth of neocortical neurons. These discoveries have kept alive the question of whether the same is true in adult humans.

If this prolonged neurogenic potential also characterizes the human brain, it raises hope of harnessing the mechanisms for restorative functions. It is no wonder then that our attention frequently returns to this phenomenon, raising the fundamental question: Does adult neurogenesis literally exist in humans? For this issue of our neuroDEVELOPMENTs newsletter, we discuss two 2022 papers that bring powerful molecular tools to bear on this phenomenon with, at first reading, completely different answers: Yes and No. Here we present a summary of these studies and comments from our Board. Many of our Board members are authors or otherwise linked to the two papers we present. Their comments help resolve this apparent contradiction and point to profound advances into understanding dentate neurogenic timing in mammals.

-Ron McKay, PhD, Chief Editor
Lieber Institute for Brain Development

-Venkata S. Mattay, MD
Managing Editor

-Michele Solis, PhD
Science Writer