Neural Stem Cell Coordination: a Developmental, Evolutionary and Circuit perspective

Introduction

The adult mammalian brain exhibits a remarkable capacity for adaptation, which has long been thought to result from synaptic remodeling of neurons born during development. Importantly, the discovery that new neurons can be generated in the adult by neural stem cells (NSCs) revolutionized our understanding of brain plasticity.

Neurogenic Regions

In the adult mouse brain, NSCs reside in two specialized niches:

1. The dentate gyrus (DG)
2. The ventricular-subventricular zone (V-SVZ) lining the lateral ventricles.

Although anatomically and functionally different, these two neurogenic regions share several cell types, including the glial NSCs and their lineage, and are sensitive to similar environmental stimuli. This raises the exciting possibility that NSCs within and between niches could coordinate their behavior under specific contexts.

Recent Findings

I recently showed that in the V-SVZ, regionally-distinct NSC pools can selectively and transiently respond to specific physiological states. However, such spatial and functional stem cell diversity in the DG remains to be investigated.

Hypothesis

Here, we hypothesize that the two brain niches form a single plasticity-generator system, comprising multiple stem cell subpopulations, some of which may be inter-dependent.

Research Objectives

We will first investigate whether some NSC pools across both niches share unexpected molecular features and developmental trajectories.

To determine whether and how this V-SVZ/DG system evolved to sustain a plasticity-oriented, regionally-restricted, and transient process in mammals, we will perform comparative transcriptomics with a contrasting model of adult neurogenesis in Zebrafish, which is regeneration-oriented, widespread, and continuous.

Finally, we will test whether the recruitment of specific adult NSCs in the mammalian brain is orchestrated by neuronal circuit activity outside the niche.

Conclusion

Altogether, our work will uncover the molecular, cellular, and circuit logic of adult mammalian neurogenesis in light of NSC heterogeneous identities.