A Distinctive layering pattern of mouse dentate granule cells is generated by developmental and adult neurogenesis

Abstract

New neurons are continuously added throughout life to the dentate gyrus of the mammalian hippocampus. During embryonic and early postnatal development, the dentate gyrus is formed in an outside-in layering pattern that may extend through adulthood. In this work we aimed to systematically quantify the relative position of dentate granule cells generated at different ages. We used 5’-bromo-2’-deoxyuridine (BrdU) and retroviral methodologies to birth-date cells born in the embryonic, early postnatal and adult hippocampus and assessed their final position in the adult mouse granule cell layer. We also quantified both developmental and adult-born cohorts of neural progenitor cells that contribute to the pool of adult progenitor cells. Our data confirm that the outside-in layering of the dentate gyrus continues through adulthood and that early-born cells constitute most of the adult dentate gyrus. We also found that a substantial fraction of the dividing cells in the adult dentate gyrus were derived from early-dividing cells and retained BrdU, suggesting that a subpopulation of hippocampal progenitors divides infrequently from early development on.

Time-lapse imaging reveals highly dynamic structural maturation of postnatally born dentate granule cells in organotypic entorhino-hippocampal slice cultures

“…DCX and calbindin rarely co-localized which indicates that DCX marked young, immature neurons while calbindin was only expressed in more mature GCs. This finding reflects the typical layering of immature neurons being located in the SGZ and the inner part of the GCL, while mature neurons are found in the outer part of the GCL, toward the molecular layer (ML)2231. The fact that at DIV 7 we found more DCX-positive cells relative to calbindin-positive cells is also congruent with the fact that this is still the time period of high cell proliferation and neurogenesis16.…”

Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

“…The GCL comprises a heterogeneous population of GCs generated at different times from development to adulthood, with more than 80 % of the GCs generated postnatally (Altman and Bayer, 1990; Mathews et al, 2010). Hence, understanding the impact of dentate gyrus (DG) activity requires dissecting the output of those distinct neuronal populations.…”

“…1A,B). Due to the pronounced decrease in DG neurogenesis that occurs during early postnatal life (Mathews et al, 2010), the neuronal population expressing ChR2 is greatly enriched in GCs generated around the time of TAM induction. In agreement with this notion, the majority of ChR2-expressing GCs (ChR2-GCs) expressed the neuronal marker calbindin and displayed mature GC morphology with complex spiny dendrites extending through the molecular layer and axons projecting through the hilus reaching the distal CA3 pyramidal layer (Fig.…”

“…We then performed whole cell recordings in unlabeled mature GCs located in the outer third of the GCL, primarily generated during development (Marin-Burgin et al, 2012; Mathews et al, 2010). Stimulation of ChR2-GCs elicited IPSCs that were also blocked by either KYN or PTX, now revealing the disynaptic feedback loop ChR2-GC → GABA interneuron → GC (Figure 1G, H1–H3).…”

Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity

“…30 The density and localization of GFP-expressing cells was similar in control and anesthesia-treated mice (Fig.1; P21 control, n=7, 241,000±26,000 GFP positive cells/ mm 3 ; P21 anesthesia, n=8, 243,000±24,000 cells/mm 3 ; P =0.961, t-test), demonstrating that progenitor cell labeling was equivalent between the two groups. Exposure to isoflurane, however, led to a dramatic increase in the number of caspase-3 immunoreactive cells in the dentate gyrus (Fig.1), consistent with previous studies.…”