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Astrogenesis in the murine dentate gyrus – a life-long and plastic process mediated by proliferation of neural stem cells and local astrocytes

ABSTRACT: Astrocytes are highly abundant cells in the mammalian brain and their numerous functions are of vital importance for all aspects of development, adaption and aging of the central nervous system (CNS). Mounting evidence indicates the astrocytes’s cardinal contribution to a wide range of neuropathies, still, our understanding of astrocyte development significantly lags behind those of other CNS cells. Using the dentate gyrus (DG) as a model system, we here combine genetic fate-mapping, behavioral paradigms, single cell transcriptomics and in vivo two-photon imaging, to assess the generation and proliferation of astrocytes across the lifespan of a mouse in great detail. Astrogenesis in the DG is initiated by perinatal radial glia-like neural stem cells (rNSCs) giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside-in-pattern. This process occurs simultaneously to neurogenesis and likewise continues life-long. In the adult DG, rNSCs occasionally give rise to newborn astrocytes, but the vast majority of astrogenesis is mediated through proliferation of local astrocytes. Interestingly, locally dividing astrocytes revealed an unexpected plasticity and were able to adapt their proliferation to environmental and behavioural stimuli. Our study thus establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamic to hippocampal plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE190399 | GEO | 2021/12/12

REPOSITORIES: GEO

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