Adult naris closure profoundly reduces tyrosine hydroxylase expression in mouse olfactory bulb

Kim

Proc. Natl. Acad. Sci. U.S.A.

et al. 2016

In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein G o is widely expressed in the MOE and VNO of mice. Early studies indicated that G o expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of G o in the MOE have remained poorly defined. Here, we examined the role of G o in the MOE using mice lacking the α subunit of G o . Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that G o signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.heterotrimeric G o protein | olfactory mucosa | olfactory bulb interneuron | tyrosine monooxygenase | sexual behavior P heromones evoke diverse social and sexual behaviors in animals of the same species. In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and vomeronasal organ (VNO). Early studies indicated that the VNO is largely responsible for the detection of pheromones and the consequent direction of social and sexual behaviors (1). VNO sensory neurons (VSNs) express distinct types of vomeronasal receptors: type 1 (V1Rs) in the apical region and type 2 (V2Rs) in the basal region. These receptors couple, respectively, to G i and G o members of the heterotrimeric GTPbinding protein family. It has been suggested that, following ligand binding to V1Rs and V2Rs, the Gβγ subunits released from G i and G o activate phospholipase C and increase the intracellular concentration of Ca 2+ . Ca 2+ ions induce opening of small Ca 2+ -activated K + (SK3) channels, subsequently activating Ca 2+ -activated Cl − channels (CACCs). In the VNO, Gβγ can also directly induce the opening of G protein-activated inward rectifying K + (GIRK) channels independently of transient receptor potential cation channel C2 (TRPC2) (2). Because of the VNO's high luminal K + concentration (2), opening of SK3 and GIRK channels leads to depolarization of VSNs and transmission of pheromone signals. Targeted deletion of the TRPC2 gene abrogates gender identification and intermale aggression without affecting male-to-female mating behavior in male mice (3, 4). Targeted deletion of the GIRK1 gene partially attenuates mating behavior of the male toward fem...

Section: Resultsmentioning

confidence: 99%

Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in G _o -deficient mice

Kim

Proc. Natl. Acad. Sci. U.S.A.

et al. 2016

“…The OD group included only those bulbs (n = 4), in which naris occlusion resulted in a significant decrease in the expression of tyrosine hydroxylase (TH), confirmed immunohistochemically (Supplementary information, Figure S4A and S4B). Despite a clear reduction in TH expression in OD bulbs, a known consequence of the naris closure [28,29], there was no significant difference in migration speed between the cells in control and OD groups (Supplementary information, Figure S4C). Similarly, we did not observe any difference in mean migration angles (Supplementary information, Figure S4D), the fraction of cells with unior multidirectional migration patterns (Supplementary information, Figure S4E), and net or cumulative distances that cells traveled in the GL (Supplementary information, Figure S4F).…”

Section: Odor Deprivation Does Not Affect the Migration Of Adultborn mentioning

confidence: 99%

Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

Liang

Riecken

et al. 2016

Cell Res

The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate.

Proc. Natl. Acad. Sci. U.S.A.

“…It might be surprising that the decrease in A:D synapses is not accompanied by a reduction in TH expression and activity (17,38). TH expression in the glomerular layer is decreased when odorant-induced activity is eliminated with naris occlusion (39) or OSN elimination (40). However, the age-related decrease in glomerular synapses may result in more subtle changes in activity that would be unlikely to affect TH expression.…”

Section: Are Morphological Changes In the Ob Related To Alterations Inmentioning

confidence: 99%

Age-induced disruption of selective olfactory bulb synaptic circuits

Richard

Taylor²,

Greer³

2010

127

125

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...