The Adult Brain Contains Dormant Precursor Neurons, Slowly Used Up Over Life

When it comes to better maintaining the aging brain, understanding the creation of new neurons in adult life is an important topic. If there are processes by which new neurons arise and are integrated into the brain, then they are targets for therapies intended to increase that output. It is generally agreed upon that a greater supply of new neurons is a good thing, and may even enhance function at all ages, not just in later life. In that context, the discussion here, regarding a precursor cell population that is slowly used up over a lifetime in order to generate new neurons, is most interesting.

Dormant non-proliferative neuronal precursors (dormant precursors) are a unique type of undifferentiated neuron, found in the adult brain of several mammalian species, including humans. Dormant precursors are fundamentally different from canonical neurogenic-niche progenitors as they are generated exquisitely during the embryonic development and maintain a state of protracted postmitotic immaturity lasting up to several decades after birth. Thus, dormant precursors are not pluripotent progenitors, but to all effects extremely immature neurons. Recently, transgenic models allowed to reveal that with age virtually all dormant precursors progressively awaken, abandon the immature state, and become fully functional neurons.

Compelling evidence implies that dormant precursors in the adult brain are physiologically relevant and may contribute to an overlooked form of late brain maturation. Intriguingly, our brain seems to use this resource sparingly throughout the whole course of life. To fully understand the contribution of dormant precursors integration, it will be crucial to identify the molecular mechanisms promoting or hindering maturation and the behavioral impacts.

Considering the possibility of a precursor-based contribution to learning and adaptation of input processing in the young individuals may shed a new light on development. The handful of dormant precursors still available up to an advanced age may also constitute a precious resource and understanding the mechanisms that promote their late integration could allow to recover every last bit of untapped potential, perhaps improving cognition and/or adaptation in the aging brain. Importantly, the number of dormant precursors is inherently limited by their non-proliferative nature and purposely promoting their integration in early life will lead to their premature exhaustion. Therefore, a comprehensive understanding of the relevance of dormant precursors in processes of brain maturation and adaptation along the different life phases constitutes a pressing need.



@Reason Are they sure that neurogenesis at the DG isn't supplying these type of cells during adulthood? These cells may differentiate at site and migrate post mitotic

Posted by: Alfi at May 9th, 2022 10:50 AM


I was thinking the inverse might be true: what has looked like neurogenesis in adult mice might turn out to be activation of dormant non-proliferative neuronal precursors. This would be upsetting, since I take it that everyone here was excited by the possibility of adult neurogenesis in humans.

Posted by: gheme at May 9th, 2022 1:17 PM

These sound like VSELs to me - left overs from embryonic development. They are resistant to exiting quiescence but eventually do so. It is not known for sure, but I suspect they operate as a sort of top level stem cells, feeding down to the lower levels in all tissues.

Posted by: Mark at May 10th, 2022 4:15 AM

This does underlie the importance of making sure interventions that aim to trigger neurogenesis are not just using up this finite supply of precursor cells too early.

Posted by: Kel at May 13th, 2022 7:23 PM
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