Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury

Abstract

SUMMARYAdult brain neural stem cells (NSCs) are conventionally regarded as rare cells restricted to two niches: the subventricular zone (SVZ) and the subgranular zone. Parenchymal astrocytes can also contribute to neurogenesis after injury, however the prevalence, distribution, and behaviour of these latent NSCs remained elusive. To tackle these issues, we reconstructed the spatiotemporal pattern of striatal astrocytes neurogenic activation after excitotoxic lesion in mice. Our results indicate that a neurogenic potential is broadly distributed throughout the striatum but is focally activated at the lesion border. In this region, similarly to canonical niches, steady state neurogenesis is ensured by the continuous stochastic activation of local astrocytes. Activated astrocytes quickly return to quiescence, while their progeny locally proliferate for about 10 days following a stochastic behaviour that features an acceleration in differentiation propensity. Notably, striatal astrocytes activation rate matches that of SVZ astrocytes indicating a comparable prevalence of NSC potential.