Importance of newly generated neurons in the adult olfactory bulb for odor discrimination

Abstract

In adult rodents, neurons are continually generated in the subventricular zone of the forebrain, from where they migrate tangentially toward the olfactory bulb, the only known target for these neuronal precursors. Within the main olfactory bulb, they ascend radially into the granule and periglomerular cell layers, where they differentiate mainly into local interneurons. The functional consequences of this permanent generation and integration of new neurons into existing circuits are unknown. To address this question, we used neural cell adhesion molecule-deficient mice that have documented deficits in the migration of olfactory-bulb neuron precursors, leading to about 40% size reduction of this structure. Our anatomical study reveals that this reduction is restricted to the granule cell layer, a structure that contains exclusively ␥-aminobutyric acid (GABA)ergic interneurons. Furthermore, mutant mice were subjected to experiments designed to examine the behavioral consequences of such anatomical alteration. We found that the specific reduction in the newly generated interneuron population resulted in an impairment of discrimination between odors. In contrast, both the detection thresholds for odors and short-term olfactory memory were unaltered, demonstrating that a critical number of bulbar granule cells is crucial only for odor discrimination but not for general olfactory functions.cell adhesion molecules ͉ neurogenesis ͉ interneurons ͉ ␥-aminobutyric acid (GABA)

Increased Neurogenesis in Adult mCD24-Deficient Mice

“…Alteration of one of these components without compensation by the others could result in a dramatic modification in the organization of the structure. This was observed for NCAM mutant mice, in which an alteration between migrating neuroblasts and their stationary environment created a reduction in OB size and a disturbance in laminar organization (Cremer et al, 1994;Gheusi et al, 2000). In mCD24-deficient mice, in spite of an overproliferation of neuronal precursor cells in the SVZ and chain-like migrating neuroblast organization conserved, we did not find any significant increase in the size of mutant OB.…”

Adult Neurogenesis and the Ischemic Forebrain

“…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).…”

Epigenetic regulation of aging stem cells

“…NSCs in the hippocampus give rise to new granule layer neurons that integrate into functional neuronal circuits (Kaplan and Bell 1984;Kempermann et al, 1998a;Gould et al, 1999;Song et al, 2002;Lagace et al, 2007) and are critical for such cognitive functions as learning and memory formation (Shors et al, 2001;Kee et al, 2007;Imayoshi et al, 2008;Zhang et al, 2008;Clelland et al, 2009). Deep layer neurons of the olfactory bulb are continuously replaced by neurons generated from the NSCs in the SVZ and play essential roles in odor discrimination and odor memory (Gheusi et al, 2000;Enwere et al, 2004;Lagace et al, 2007;Breton-Provencher et al, 2009). In humans, adult neural progenitors have been identified in the dentate gyrus and lateral ventricles (Eriksson et al, 1998;Kukekov et al, 1999;Roy et al, 2000;Sanai et al, 2004;Curtis et al, 2007), although their role in cognition has not been established.…”