C.A. Greer

Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region- and layer-specific alterations of neuron morphology and/or synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse. Cognitive aspects of olfactory function, particularly acuity, can decline during aging. However, due to ongoing adult neurogenesis, the olfactory system also undergoes a profound and continuous remodeling of synaptic circuits throughout life. This raises the question of whether during remodeling of olfactory circuits a decrease in cell number or synaptic organization may contribute to cognitive deficits. To assess the effect of aging on the organization of olfactory bulb (OB) circuitry we carried out quantitative morphometric analyses in the mouse OB at 2, 6, 12, 18 and 24 months. Our data establish that the volumes of the major OB layers do not change during aging. In parallel, we demonstrate for the first time that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide the first evidence of the stability of projection neurons and interneurons subpopulations in the aging mouse OB, arguing against the notion of an age-dependent widespread loss of neurons. Finally, we show ultrastructurally a significant layer-specific loss of synapses; synaptic density is reduced in the glomerular layer but not the external plexiform layer, leading to an imbalance in OB circuitry. These results suggest that reduction of afferent synaptic input and local modulatory circuit synapses in OB glomeruli may contribute to specific age-related alterations of the olfactory function.

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Mitral cells
Granule cells