Characterization and modulation of “immature” neurons: a potentially exploitable reservoir of non-newly generated cells involved in plasticity of the rodent and human cerebral cortex

The mammalian brain is rather incapable of performing cell renewal and consequently can hardly repair itself or counteract the damage of aging, especially in humans. Brain plasticity is considered as a major tool for obtaining these goals, being required for learning, memory, reduction of impact of brain aging and recovery from brain damage. Neural plasticity is ensured by the rewiring of neural connections and, to a lesser extent, by the addition of new neurons produced by stem cells (adult neurogenesis). Recently, a great interest was aroused by the discovery of a new population of adult cortical “immature neurons” (cINs) that are born pre-natally, then continuing to express markers of immaturity shared with adult newlyborn neurons. These cINs ideally represent a new form of delayed neurogenesis (“without division”) involving neural elements “frozen” in a standby, undifferentiated mode before birth. They might represent a potential reservoir of young cells with a still unidentified role in an adult brain region lacking neural stem cells: the cerebral cortex. The cINs were thought to be restricted to the piriform cortex of rodents, yet an unexpected twist occurred recently, when Unit 1 of this project showed high phylogenetic variation in mammals, with abundant occurrence in the neocortex of large-brained, gyrencephalic species (La Rosa et al., eLife 2020). This finding opens the exciting avenue for a form of structural plasticity mimicking adult neurogenesis in the cortical mantle, nevertheless very little is known about the physiological function/modulation/mobilization of these cells. Data obtained using DCX-Cre-ERT2/Flox-EGFP transgenic animals, a reporter mouse line for cINs, confirmed that cINs do not die with age. On the contrary, most of them mature as cells with more complex dendritic arborisation and integrate into the piriform cortex network.