Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit.

Odorant receptors (OR) are strongly implicated in coalescence of olfactory sensory neuron (OSN) axons and the formation of olfactory bulb (OB) glomeruli. However, when ORs are first expressed relative to basal cell division and OSN axon extension is unknown. We developed an in vivo fate-mapping strategy that enabled us to follow OSN maturation and axon extension beginning at basal cell division. In parallel, we mapped the molecular development of OSNs beginning at basal cell division, including the onset of OR expression. Our data show that ORs are first expressed around 4 d following basal cell division, 24 h after OSN axons have reached the OB. Over the next 6+ days the OSN axons navigate the OB nerve layer and ultimately coalesce in glomeruli. These data provide a previously unidentified perspective on the role of ORs in homophilic OSN axon adhesion and lead us to propose a new model dividing axon extension into two phases. Phase I is OR-independent and accounts for up to 50% of the time during which axons approach the OB and begin navigating the olfactory nerve layer. Phase II is OR-dependent and concludes as OSN axons coalesce in glomeruli.olfactory epithelium | axon guidance | tamoxifen | olfactory marker protein | Ascl1 I n the mouse olfactory system, olfactory sensory neurons (OSNs) extend their axons from the olfactory epithelium (OE) to the olfactory bulb (OB), where they converge to form glomeruli. Each OSN expresses only 1 of ∼2,400 candidate odorant receptor (OR) alleles. OSNs expressing the same OR can be widely dispersed in the OE, yet their axons converge in only two to three molecularly specific glomeruli of a possible 3,700 (1). It was first recognized almost 20 y ago that substituting an OR-coding region with that of a different OR resulted in the glomerular convergence of axons at an ectopic location relative to that of the native ORs (2). This led to the suggestion that ORs have an instructive role in the extension and glomerular coalescence of OSN axons, most likely mediated by homophilic fasciculation (3-5).Postnatal OSNs are derived from self-renewing precursors located proximal to the deep basal lamina of the OE (6). Following the division of globose basal stem cells, OSN neuroblasts transiently express Achaete-scute homolog 1 (Ascl1) followed by two phases of differentiation (6-8). Initially, they express growthassociated protein-43 (GAP-43), a marker of immature cells. Subsequently, the OSNs down-regulate GAP-43 and express olfactory marker protein (OMP), a universal marker of mature OSNs.Although there is a consensus on the involvement of ORs in OSN axon glomerular convergence, when ORs exert that influence following basal cell division or axon extension is not known. Moreover, the developmental progression of GAP-43 to OMP, as a measure of OSN differentiation and maturation, or of adenylate cyclase 3 (AC3), a downstream signaling molecule also implicated in axon extension, has not been considered in the context of OR expression or OSN dynamics. Here, we determined when ORs exert thei...

With advancing age, the ability of humans to detect and discriminate odors declines. In light of the rapid progress in analyzing molecular and structural correlates of developing and adult olfactory systems, the paucity of information available on the aged olfactory system is startling. A rich literature documents the decline of olfactory acuity in aged humans, but the underlying cellular and molecular mechanisms are largely unknown. Using animal models, preliminary work is beginning to uncover differences between young and aged rodents that may help address the deficits seen in humans, but many questions remain unanswered. Recent studies of odorant receptor (OR) expression, synaptic organization, adult neurogenesis, and the contribution of cortical representation during aging suggest possible underlying mechanisms and new research directions.