Humans and Mice Express Similar Olfactory Preferences

In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.     

The Evolution of Mammalian Olfactory Receptor Genes

We performed a comparative study of four subfamilies of olfactory receptor genes first identified in the dog to assess changes in the gene family during mammalian evolution, and to begin linking the dog genetic map to that of humans. The human subfamilies were localized to chromosomes 7, 11, and 19. The two subfamilies that were tightly linked in the dog genome were also tightly linked in the human genome. The four subfamilies were compared in human (primate), horse (perissodactyl), and a variety of artiodactyls and carnivores. Some changes in gene number were detected, but overall subfamily size appeared to have been established before the divergence of these mammals 60-100 million years ago.     

Modeling Olfactory Bulb Evolution through Primate Phylogeny

Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution.     

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of females. Our study provides additional evidence in support of genotype-dependent maternal influences on phenotypic variability in adulthood.     

Stink Bug Aldehydes

The odorus and physiologically active substances of the secretions of Japanese stink bugs (six kinds of Pentatomidae and three kinds of Coreidae bugs) were identified. The secretions of Pentatomidae bugs contained trans 2-decenal as a main component. In the secretions of Coreidae bugs n-hexanal was always found and in the case of Acanthocoris sordidus trans 2-hexenal was a main component.     

Loss of Olfactory Receptor Function in Hominin Evolution

The mammalian sense of smell is governed by the largest gene family, which encodes the olfactory receptors (ORs). The gain and loss of OR genes is typically correlated with adaptations to various ecological niches. Modern humans have 853 OR genes but 55% of these have lost their function. Here we show evidence of additional OR loss of function in the Neanderthal and Denisovan hominin genomes using comparative genomic methodologies. Ten Neanderthal and 8 Denisovan ORs show evidence of loss of function that differ from the reference modern human OR genome. Some of these losses are also present in a subset of modern humans, while some are unique to each lineage. Morphological changes in the cranium of Neanderthals suggest different sensory arrangements to that of modern humans. We identify differences in functional olfactory receptor genes among modern humans, Neanderthals and Denisovans, suggesting varied loss of function across all three taxa and we highlight the utility of using genomic information to elucidate the sensory niches of extinct species.     

Neuropeptide S Facilitates Mice Olfactory Function through Activation of Cognate Receptor-Expressing Neurons in the Olfactory Cortex

Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR). High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v.) injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir) neurons that also bear NPSR. NPS (0.1–1 nmol) i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val⁵]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON), piriform cortex (Pir), ventral tenia tecta (VTT), the anterior cortical amygdaloid nucleus (ACo) and lateral entorhinal cortex (LEnt). The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice.     

The Evolution of Olfactory Capabilities in Wild Birds: A Comparative Study

Modern birds possess an olfactory apparatus similar to that of other vertebrates, yet the major evolutionary forces that drove the evolution of diversity in olfactory capabilities in birds remain elusive. Several non-mutually exclusive evolutionary scenarios for the evolution of olfactory capability in birds have been proposed. Olfactory capability may have evolved due to its role in recognition in social contexts. In addition, olfactory capability may have evolved because it provides a selective advantage in foraging or navigation. Finally, olfactory capability could be favored whenever the ecological conditions of species hindered the use of other senses and/or favored olfaction. Here we evaluate predictions from these hypotheses in a comparative study using a species-level phylogeny of 142 bird species and considering the indirect effects of some predictors on others. We find an interactive effect of aquatic dependence and diet on the size of the olfactory bulb: vegetarian and omnivore birds living in aquatic environments have larger olfactory bulbs than terrestrial birds, whereas species with an animal diet, aquatic and terrestrial species have similar-sized olfactory bulbs. In addition, the size of the olfactory bulb was weakly related with social complexity, with colonial species having relatively larger olfactory bulb than solitary breeders or those forming small aggregations. Our results suggest that the role of foraging in driving enhancements in the avian olfactory apparatus is contingent on ecological conditions that may affect the transmission of odor-based signals. This provides evidence for the largely neglected possibility that the evolution of the olfactory apparatus of birds has been driven by the interaction between ecological and behavioral traits, rather than being solely due to main effects of these traits.     

Norepinephrine Is Lateralized Within the Olfactory Bulbs of Male Mice

Abstract: Concentrations and in vitro release of norepinephrine were determined from left and right olfactory bulbs of adult male CD-1 mice. Norepinephrine concentrations from the left olfactory bulbs were significantly greater than those of the right ( p < 0.01). No statistically significant differences were obtained for dopamine, nor were there differences in tissue weights between the left and right olfactory bulb tissue samples. To verify further this asymmetry, release rates of norepinephrine were measured from superfused left and right olfactory bulbs. Norepinephrine output from the left olfactory bulb was significantly greater than that from the right ( p < 0.05). These results show that norepinephrine is lateralized within the olfactory bulbs of male mice. This asymmetry shows a clear catecholamine specificity with regard to concentrations and may be related to the lateralized olfactory processing that has been reported to occur in humans.     

Olfactory Bulbectomy Leads to the Development of Epilepsy in Mice

There is a clear link between epilepsy and depression. Clinical data demonstrate a 30–35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals. Studies assessing pro-epileptogenic changes in models of depression, however, are more limited. Here, we examined whether a traditional rodent depression model—bilateral olfactory bulbectomy—predisposes the animals towards the development of epilepsy. Past studies have demonstrated increased neuronal excitability after bulbectomy, but continuous seizure monitoring had not been conducted. For the present study, we monitored control and bulbectomized animals by video-EEG 24/7 for approximately two weeks following the surgery to determine whether they develop spontaneous seizures. All seven bulbectomized mice exhibited seizures during the monitoring period. Seizures began about one week after surgery, and occurred in clusters with severity increasing over the monitoring period. These results suggest that olfactory bulbectomy could be a useful model of TBI-induced epilepsy, with advantages of relatively rapid seizure onset and a high number of individuals developing the disease. The model may also be useful for investigating the mechanisms underlying the bidirectional relationship between epilepsy and depression.     

Transsynaptic Regulation of Olfactory Bulb Catecholamines in Mice and Rats

Norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured simultaneously by high performance liquid chromatography with electrochemical detection in extracts of olfactory bulbs at various intervals after chemical or surgical deafferentation. Chemical deafferentation of mice by intranasal irrigation with Triton X-100 or of rats by olfactory axotomy resulted in a rapid progressive decline of DA and DOPAC and an associated rise in NE in the olfactory bulb. However, after several weeks, these values returned to prelesion levels concomitant with reinnervation of the bulb by the afferent neurons. In contrast, deafferentation by procedures known to prevent reinnervation of the bulb by the afferent chemoreceptor neurons (i.e., a ZnSo4 solution in mice or a surgical procedure in rats) completely blocked the return to pre-lesion values of DA, DOPAC, and NE. The specificity of these effects was demonstrated by the inability of intranasal administration of the neurotoxin 6-hydroxydopamine to alter DA levels, resulting instead in a significant decline in olfactory bulb NE content. These data demonstrate that the DA content of the olfactory bulb can be influenced by either chemical or surgical modulation of the afferent pathway in two different species. This offers additional support for our hypothesis of transsynaptic regulation of intrinsic DA neurons of the bulb by the afferent olfactory chemoreceptor neurons.     

Mitochondrial DNA Evolution in Mice

This study extends knowledge of mitochondrial DNA (mtDNA) diversity in mice to include 208 animals belonging to eight species in the subgenus Mus. Highly purified mtDNA from each has been subjected to high-resolution restriction mapping with respect to the known sequence of one mouse mtDNA. Variation attributed to base substitutions was encountered at about 200 of the 300 cleavage sites examined, and a length mutation was located in or near the displacement loop. The variability of different functional regions in this genome was as follows, from least to most: ribosomal RNA, transfer RNA, known proteins, displacement loop and unidentified reading frames.—Phylogenetic analysis confirmed the utility of the Sage and Marshall revision of mouse classification, according to which there are at least four species of commensal mice and three species of aboriginal mice in the complex that was formerly considered to be one species. The most thoroughly studied of these species is Mus domesticus, the house mouse of Western Europe and the Mediterranean region, which is the mitochondrial source of all 50 of the laboratory strains examined and of the representatives of wild house mice introduced by Europeans to North and South America during the past few hundred years.—The level of mtDNA variation among wild representatives of (M. musculus) and several other mammalian species. By contrast, among the many laboratory strains that are known or suspected to stem from the pet mouse trade, there is little interstrain variation, most strains having the "old inbred" type of domesticus mtDNA, whose frequency in the 145 wild mice examined is low, about 0.04. Also notable is the apparent homogeneity of mtDNA in domesticus races that have fixed six or more fused chromosomes and the close relationship of some of these mtDNAs to those of karyotypically normal mice.—In addition, this paper discusses fossil and other evidence for the view that in mice, as in many other mammals, the average rate of point mutational divergence in mtDNA is 2–4% per million years. From this, it is estimated that the commensal association between mice and our ancestors began more than a million years ago, i.e., at an early stage in the evolution of Homo erectus.     

Photoperiod Mediated Changes in Olfactory Bulb Neurogenesis and Olfactory Behavior in Male White-Footed Mice (Peromyscus leucopus)

Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.     

A Dysfunctional Sense of Smell: The Irreversibility of Olfactory Evolution in Free-Living Pigs

Artificial selection began to override natural selection in domesticated wild boar and other species about 10,000 years ago. The intentional selection of a desired phenotypic trait is a complex process, and comes along with unexpected or even unwanted changes in other traits, because of epistatic gene effects, and ontogenetic constraints. The loss of brain mass in domestic ungulates is related to selection for reduced reaction to external stimuli. Evolutionary losses in body structures and genes were once considered mostly irreversible, in keeping with Dollo’s law. Here we studied the biochemical and the histological functioning of the free-living pigs (FLPs) olfactory system, to see if and to what extent does FLPs regain a full sense of smell, as compared to the domestic pigs and wild boar Sus scrofa. In our samples both wild boars and FLPs have significantly larger brain per unit mass than domestic pigs, and FLPs’ brains are not significantly smaller than wild boar’s. Similarly, both wild boars and FLPs have significantly higher cell density than domestic pigs in the olfactory mucosa. Yet, at the functional level, olfactory marker protein and neuropeptide Y, both of which are important to the correct functioning of the sense of smell, are fully expressed only in wild boar. These results suggest that FLPs reacquired structural, but not the biochemical capability in their olfactory system.     

The Temporal Expression Pattern of Alpha-Synuclein Modulates Olfactory Neurogenesis in Transgenic Mice

Background

Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS) under the murine Thy1 (mThy1) promoter, a model known to have a particularly high tg expression associated with impaired olfaction.

Results

Survival of newly generated neurons (NeuN-positive) in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor β (PDGF) promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.

Conclusions

The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.