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 layerspecific alterations of neuron morphology and 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. 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 mo. Our data establish that the volumes of the major OB layers do not change during aging. Parallel to this, we are unique in demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide unique 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.aging | axodendritic synapses | dendrodendritic synapses | mitral cells A ge-related neurodegenerative diseases, such as Parkinson and Alzheimer's, involve localized or widespread neuronal loss, but little is known about the changes occurring in the brain during normal aging. A growing consensus argues against widespread neuronal loss and atrophy during aging (1, 2). Rather, subtle region-and layer-specific alterations of neuronal morphology and synaptic connections are reported in the neocortex and hippocampus, where they may contribute to age-related cognitive deficits.The laminar organization of olfactory bulb (OB) neurons and synapses provides a simplified cortical model in which we can probe principles of neuronal and synaptic organization during aging. Sensory functions are affected by aging, including alterations in olfactory acuity, discrimination, and memory (3-12). The OB is the first central relay in the pathway processing odor information: it receives afferent input from olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) and is responsible for detecting odors in the nasal cavity. OSN axons synapse on mitral/tufted cell dendrites in OB glomerular neuropils. OB local interneurons modulate the activity of mitral/tufted cells, contributing to odor signal integration, before propagation to the piriform cortex. Projections from the OE to the OB are organized in an odor receptor (OR) map; each subpopulation of OSNs expressin...

The piriform cortex (PCX) is a trilaminar paleocortex that is of interest for its role in odor coding and as a model for studying general principles of cortical sensory processing. While the structure of the mature PCX has been well characterized, its development is poorly understood. Notably, the kinetics as well as the cellular and morphological basis of the postnatal events that shape the PCX remain unknown. We followed the cellular fates of early- versus late-born cells in layer II of the anterior PCX, with a focus on the molecular maturation of pyramidal cells and the kinetics of their differentiation. We showed that: 1) early-born pyramidal cells differentiate more rapidly than late-born cells and 2) the position of pyramidal cells within the thickness of layer II determines the kinetics of their molecular maturation. We then examined the postnatal development of cortical lamination and showed that the establishment of inhibitory networks in the PCX proceeds through an increase in the density of inhibitory synapses despite a decrease in the number of interneurons. Together, our results provide a more comprehensive view of the postnatal development of the anterior PCX and reveal both similarities and differences in the development of this paleocortex versus the neocortex.

Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice.