Cellular Plasticity in the Adult Murine Piriform Cortex: Continuous Maturation of Dormant Precursors Into Excitatory Neurons

Abstract

Neurogenesis in the healthy adult murine brain is based on proliferation and integration of stem/progenitor cells and is thought to be restricted to 2 neurogenic niches: the subventricular zone and the dentate gyrus. Intriguingly, cells expressing the immature neuronal marker doublecortin (DCX) and the polysialylated-neural cell adhesion molecule reside in layer II of the piriform cortex. Apparently, these cells progressively disappear along the course of ageing, while their fate and function remain unclear. Using DCX-CreERT2/Flox-EGFP transgenic mice, we demonstrate that these immature neurons located in the murine piriform cortex do not vanish in the course of aging, but progressively resume their maturation into glutamatergic (TBR1+, CaMKII+) neurons. We provide evidence for a putative functional integration of these newly differentiated neurons as indicated by the increase in perisomatic puncta expressing synaptic markers, the development of complex apical dendrites decorated with numerous spines and the appearance of an axonal initial segment. Since immature neurons found in layer II of the piriform cortex are generated prenatally and devoid of proliferative capacity in the postnatal cortex, the gradual maturation and integration of these cells outside of the canonical neurogenic niches implies that they represent a valuable, but nonrenewable reservoir for cortical plasticity.

Non-proliferative neurogenesis in human periodontal ligament stem cells

“…In addition, it is important to note that almost none of these labeled new born neurons show mitotic chromosomes or mitotic spindle to really confirm that adult neurogenesis occurs progressively through sequential phases of proliferation 43,[47][48][49][50][51][52][53] . Importantly, the existence of non-proliferative neuronal precursors in several brain areas has also been observed 76,77 . Moreover, the self-renewal and multipotent properties demonstrated by NSC in vitro 78 have not been clearly demonstrated in vivo 54,67,79 .…”

Brain Structural Plasticity: From Adult Neurogenesis to Immature Neurons

“…For instance, markers of stem cells (Sox2, nestin) or newborn neurons (DCX, PSA-NCAM) are abundant in these cell categories but not exclusively associated with them, being detectable also in other contexts. The cytoskeletal protein DCX is also abundant in cells that are born prenatally, and then remain undifferentiated for long times by continuing to express immaturity molecules (INs, Gómez-Climent et al, 2008;Bonfanti and Nacher, 2012;König et al, 2016;Piumatti et al, 2018;Rotheneichner et al, 2018; Figures 1B-D). Considering DCX as FIGURE 1 | Shared aspects and differences in neurogenic and non-neurogenic processes.…”

Early migration of precursor neurons initiates cellular and functional regeneration after spinal cord injury in zebrafish

“…Similarly, we detect expression of HuC and PSA-NCAM in ependymal cells and cells recruited to the injury site during homeostasis and after injury. Intriguingly, delayed neurogenesis and neural precursors have recently been found in diverse brain regions of mammals (Luzzati et al, 2014, Piumatti et al, 2018, Rotheneichner et al, 2018. Furthermore, enigmatic cells with immature neuronal characteristics have frequently been reported after injury in diverse mammalian models (Lindvall and Kokaia, 2015).…”

“…Enigmatic neurons with immature characteristics have been observed in the mammalian (Luzzati et al, 2014, Piumatti et al, 2018, Rotheneichner et al, 2018 and have been proposed to participate in tissue repair in the CNS (Kempermann, 2008, Bonfanti, 2011, Kempermann, 2012. Intriguingly, precursors described as immature neurons in "standby mode" have been reported in the spinal cord of turtle and rat (Russo et al, 2004, Marichal et al, 2009.…”