Long‐term survival and cell death of newly generated neurons in the adult rat olfactory bulb

Abstract

In the adult rat olfactory bulb, neurons are continually generated from progenitors that reside in the lateral ventricle wall. This study investigates long-term survival and cell death of newly generated cells within the adult olfactory bulb. After injecting rats at 2 months of age with 5-bromodeoxyuridine (BrdU), the newly generated cells were quantified over a period of 19 months. A peak of BrdU-positive cells was reached in the olfactory bulb 1 month after BrdU injection, when all new cells have finished migrating from the ventricle wall. Thereafter, a reduction of BrdU-positive cells to about 50% was observed and it was confirmed by dUTP-nick end-labelling (TUNEL) that progenitors and young neurons undergo programmed cell death. However, cells that survived the first 3 months after BrdU injection persisted for up to 19 months. The majority of the BrdU-positive cells that reach the olfactory bulb differentiate into granule cells, but a small fraction migrate further into the glomerular layer. These newborn cells differentiate more slowly into periglomerular interneurons, with a delay of more than 1 month when compared to the granule cells. The newly generated periglomerular neurons, among them a significant fraction of dopaminergic cells, showed a similar decline in number compared to the granule cell layer and long-term survival for the remaining new neurons of up to 19 months. Rather than replacing old neurons, this data suggests that adult olfactory bulb neurogenesis utilizes the overproduction and turnover of young neurons, which is reminiscent of the cellular dynamics observed during brain development.

Histone deacetylases 1 and 2 are expressed at distinct stages of neuro‐glial development

“…Similarly in the OB, HDAC2 is expressed in NeuNpositive neurons of the granule cell layer, as well as Mitral/Tufted cells and periglomerular neurons (Fig. 4G), which do not express NeuN (Mullen et al, 1992;Winner et al, 2002). HDAC2 is not detected, however, within GFAP-positive glia surrounding the hippocampal formation or in the corpus callosum (Fig.…”

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

“…Many of these adult-born neurons eventually position within the glomerular layer of the OB and differentiate into GABAergic periglomerular interneurons, express unique marker subsets, 35 and survive for an extended period of time (over a year) 25 . In order to determine if migration of newly generated neurons to the final position in the OB is disrupted in Dcx knockout mice, we repeated the BrdU injections at P28, and then sacrificed animals 4 weeks later.…”

Adult Neurogenesis and the Ischemic Forebrain

“…On reaching the olfactory bulb subependymal region, they disperse radially to their final destinations in the granular and glomerular layers. Adult-born granular and periglomerular interneurons survive long term (Winner et al, 2002) and appear to integrate into bulb circuitry (Carlén et al, 2002;Carleton et al, 2003). As with adult-generated DGCs, the function of persistent olfactory bulb neurogenesis is largely unknown, but increasing evidence supports a role for the new neurons in olfactory memory or odor discrimination (Gheusi et al, 2000;Petreanu and Alvarez-Buylla, 2002;Rochefort et al, 2002).…”