Encoding of odors by mammalian olfactory receptors

Olfactory receptors (ORs) constitute the largest multi-gene family in the mammalian genome, with hundreds to thousands of loci in humans and mice respectively. The rapid expansion of this massive family of genes has been generated by numerous duplication and diversification events throughout evolutionary history. This size, similarity, and diversity has made it challenging to define the principles by which ORs encode olfactory stimuli. Here, we performed a broad surveying of OR responses, using an in vivo strategy, against a diverse panel of odorants. We then used the resulting interaction profiles to uncover relationships between OR responses, odorants, odor molecular properties, and OR sequences. Our data and analyses revealed that ORs generally exhibited sparse tuning towards odorants and their molecular properties. Odor molecular property similarity between pairs of odorants was informative of odor response similarity. Finally, ORs sharing response to an odorant possessed amino acids at poorly conserved sites that exhibited both, predictive power towards odorant selectivity and convergent evolution. The localization of these residues occurred primarily at the interface of the upper halves of the transmembrane domains, implying that canonical positions govern odor selectivity across ORs. Altogether, our results provide a basis for translating odorants into receptor neuron responses for the unraveling of mammalian odor coding.

EEG features in patients with Parkinson's disease during directional perception of olfactory stimuli

Introduction. Olfactory dysfunction is considered to be an early and relatively important marker of Parkinson's disease (PD). Olfactory studies using objective neurophysiological methods may become one of the diagnostic tests to identify individuals with a high risk of developing PD. The aim of the study was to assess the spectral and topographic characteristics of bioelectrical brain activity in patients with PD during directional perception of olfactory stimuli. Materials and methods. This study included 30 patients with PD (mean age was 66.5 6.5 years). The control group consisted of 20 people without PD (mean age was 65.3 8.5 years). Lavender oil, clove oil, camphor oil and -mercaptoethanol solution (an aversive stimulus) were used for olfactory stimulation, while distilled water was used as a control test. The test subject sat with their eyes closed and inhaled the presented smell for 30 seconds, while an EEG recording was made during this time. Study results. Olfactory stimulation in patients with PD showed increased synchronicity of the 3 rhythm in the right hemisphere, as well as the rhythm in the parieto-occipital regions of both hemispheres. These changes indicate significant activation of internal (endogenous) attention, increased overall, non-specific readiness potential, as well as the involvement of the limbic-reticular complex in olfactory perception. Olfactory perception in the control group was accompanied by reduction in the 1 rhythm amplitude in the parieto-occipital regions bilaterally, which may indicate moderate activation of external (exogenous) attention and the posterior attention system responsible for simple perception processes. Conclusion. Increased 3 rhythm amplitude in the right hemisphere and increased rhythm amplitude, observed during directional olfactory perception, may indicate olfactory dysfunction and should be viewed as an additional indicator when establishing a diagnosis of Parkinsons disease.

Different armpits under my new nose: olfactory sex but not gender affects implicit measures of embodiment

Research has shown that conflicting multisensory signals may alter embodiment to the point of self-identifying with a foreign body, but the role of olfaction in this process has been overlooked. Here, we study in healthy participants how sex (male and female sweat odors) and gender (male and female cosmetic scents) olfactory stimuli contribute to embodiment. Participants saw from the perspective of a sex mismatching person in virtual reality and received synchronous visuo-tactile stimulation to elicit illusory embodiment of the seen body while smelling either sex- or gender- congruent stimuli. We assessed implicit (skin conductance responses to visual threats) and explicit (questionnaire) measures of embodiment. Stronger responses to threat were found when participants smelled the sex-congruent compared to the sex-incongruent odor, while no such differences were found for the cosmetic scents. According to the questionnaire, embodiment did not differ between conditions. Post-experimental assessment of the presented cues, suggest that while both sweat odors were considered generally male, cosmetic scents were not. The presented scents were generally not associated to the embodied body. Our results suggest that sex-related body odors influence implicit but not explicit aspects of embodiment and are in line with unique characteristics of olfaction in other aspects of cognition.

Human Primary Olfactory Amygdala Subregions Form Distinct Functional Networks, Suggesting Distinct Olfactory Functions

Three subregions of the amygdala receive monosynaptic projections from the olfactory bulb, making them part of the primary olfactory cortex. These primary olfactory areas are located at the anterior-medial aspect of the amygdala and include the medial amygdala (MeA), cortical amygdala (CoA), and the periamygdaloid complex (PAC). The vast majority of research on the amygdala has focused on the larger basolateral and basomedial subregions, which are known to be involved in implicit learning, threat responses, and emotion. Fewer studies have focused on the MeA, CoA, and PAC, with most conducted in rodents. Therefore, our understanding of the functions of these amygdala subregions is limited, particularly in humans. Here, we first conducted a review of existing literature on the MeA, CoA, and PAC. We then used resting-state fMRI and unbiased k-means clustering techniques to show that the anatomical boundaries of human MeA, CoA, and PAC accurately parcellate based on their whole-brain resting connectivity patterns alone, suggesting that their functional networks are distinct, relative both to each other and to the amygdala subregions that do not receive input from the olfactory bulb. Finally, considering that distinct functional networks are suggestive of distinct functions, we examined the whole-brain resting network of each subregion and speculated on potential roles that each region may play in olfactory processing. Based on these analyses, we speculate that the MeA could potentially be involved in the generation of rapid motor responses to olfactory stimuli (including fight/flight), particularly in approach/avoid contexts. The CoA could potentially be involved in olfactory-related reward processing, including learning and memory of approach/avoid responses. The PAC could potentially be involved in the multisensory integration of olfactory information with other sensory systems. These speculations can be used to form the basis of future studies aimed at clarifying the olfactory functions of these under-studied primary olfactory areas.

Differential diagnosis of tension headache and basic principles of treatment

Headache (cephalalgia) is one of the most common symptoms and is a manifestation of more than 50 diseases. According to the World Health Organization, at least one episode of headache during a lifetime has occurred in almost every inhabitant of the Earth, and about half of them noted periodic headaches. In its etiology, cephalalgia can be primary, not associated with organic damage to tissues and organs, and secondary, which is based on pathological changes. In particular, cephalalgia in inflammatory lesions of the paranasal sinuses, brain tumors, encephalitis and meningitis, acute cerebrovascular accident, head trauma, arterial hypertension, aneurysm of the cerebral vessels, etc., should be attributed to the secondary headache. In 95–97 % of cases, the headache is not based on organic lesion, and in this case, the headache is primary. Primary cephalalgia can be based on both vegetative-vascular and metabolic-destructive changes. Primary headache can be noted with emotional or physical overstrain, exposure to a number of light, sound or olfactory stimuli, liquorodynamic or dysmetabolic disorders, when taking certain medications. Conventionally, primary headache can be divided into three groups — tension headache, migraine and cluster headache.

Specificity of California mouse pup vocalizations in response to olfactory cues

In rodents, young pups communicate with their parents through harmonic calls and ultrasonic vocalizations (USVs). These forms of communication can improve chances of survival, since pups rely on their parents for thermoregulation, nutrition and protection. The extent to which pups modulate calls in response to their surroundings remains unclear. In this study we examined whether olfactory stimuli influence characteristics of pup calls, and how these calls may be affected by pup sex and litter size, in the California mouse (Peromyscus californicus). Pups were isolated and audio recorded during an initial, 3-minute control period, after which they were exposed for 5 minutes to bedding containing one of 4 olfactory cues: scent from their home cage, scent from the home cage of an unfamiliar family, coyote urine, or no scent. Latency to call, call rate, call duration and call characteristics (e.g. frequency and amplitude) were compared between the control period and olfactory-exposure period as well as among olfactory conditions. Pups from 2-pup litters called more quietly (lower amplitude) when exposed to odor from a predator while pups from 3-pup litters called louder (higher amplitude). Additionally, pups tended to reduce their call rates in response to odors from their home cage, consistent with contact quieting. However, pups tended to increase their rate of calling when exposed to predator urine, in contrast to the expectations of predator-induced vocal suppression. Lastly, male pups produced higher-frequency calls and more USVs than females. These results indicate that a number of pup call characteristics in this species can be influenced by acute olfactory stimuli as well as factors such as litter size and sex. The value of these pup call variations for offspring-parent communication is unclear: whether they elicit different parental responses is unknown and would be an interesting/valuable/informative avenue for future studies.

Augmented reality flavor: cross-modal mapping across gustation, olfaction, and vision

Gustatory display research is still in its infancy despite being one of the essential everyday senses that human practice while eating and drinking. Indeed, the most important and frequent tasks that our brain deals with every day are foraging and feeding. The recent studies by psychologists and cognitive neuroscientist revealed how complex multisensory rely on the integration of cues from all the human senses in any flavor experiences. The perception of flavor is multisensory and involves combinations of gustatory and olfactory stimuli. The cross-modal mapping between these modalities needs to be more explored in the virtual environment and simulation, especially in liquid food. In this paper, we present a customized wearable Augmented Reality (AR) system and olfaction display to study the effect of vision and olfaction on the gustatory sense. A user experiment and extensive analysis conducted to study the influence of each stimulus on the overall flavor, including other factors like age, previous experience in Virtual Reality (VR)/AR, and beverage consumption. The result showed that smell contributes strongly to the flavor with less contribution to the vision. However, the combination of these stimuli can deliver richer experience and a higher belief rate. Beverage consumption had a significant effect on the flavor belief rate. Experience is correlated with stimulus and age is correlated with belief rate, and both indirectly affected the belief rate.

Coding of social odors in the hippocampal CA2 region as a substrate for social memory

The ability to encode and update information about individuals is critical for lasting social relationships. Although the hippocampus is important for social recognition memory, its underlying neural representations remain elusive. Here we investigate the neural codes mediating social recognition and learning by examining social odor recognition and associative odor-reward learning in mice. We performed high-resolution calcium imaging from the hippocampal CA2 region of awake head-fixed mice, as CA2 is necessary for social recognition memory. We find that CA2 encodes specific neural representations of novel social odors that are further refined during associative odor-reward learning. Optogenetic silencing of CA2 impairs the formation of reward associations. Furthermore, CA2 population activity represents odors in a geometry that enables abstract representations of social versus non-social odors. Thus, CA2 distinguishes multiple forms of olfactory stimuli to enhance the learning of social odors and associations, which are poised to serve as substrates of social memory.

Effects of Sleep Deprivation by Olfactorily Induced Sexual Arousal Compared to Immobilization Stress and Manual Sleep Deprivation on Neuromessengers and Time Keeping Genes in the Suprachiasmatic Nuclei and Other Cerebral Entities of Syrian Hamsters—An Immunohistochemical Study

We investigated the effects of sexual arousal induced by olfactory stimuli on the expression of neuromodulators, neurotransmitters and sexual steroid receptors in the suprachiasmatic nucleus (SCN, the circadian pacemaker of mammals) and other cerebral entities of Syrian hamsters (Mesocricetus auratus) compared to manual sleep deprivation and immobilization stress. The hamsters kept under a 12:12 hours (h) light:dark cycle were deprived of sleep by sexual stimulation, gentle manual handling or immobilization stress for 1 h at the beginning of the light phase and subsequently sacrificed at zeitgeber time 01:00, respectively; for comparison, hamsters were manually sleep deprived for 6 or 20 h or sacrificed after completing a full sleep phase. As demonstrated by immunohistochemistry, apart from various alterations after manual sleep deprivation, sexual stimulation caused down-regulation of arginine-vasopressin (AVP), vasointestinal peptide (VIP), serotonin (5-HT), substance P (SP), and met-enkephalin (ME) in the SCN. Somatostatin (SOM) was diminished in the medial periventricular nucleus (MPVN). In contrast, an increase in AVP was observed in the PVN, that of oxytocin (OXY) in the supraoptic nucleus (SON), of tyrosine-hydroxylase (TH) in the infundibular nucleus (IN), and dopamine beta-hydroxylase (DBH) in the A7 neuron population of the brain stem (A7), respectively. Testosterone in plasma was increased. The results indicate that sexual arousal extensively influences the neuropeptide systems of the SCN, suggesting an involvement of the SCN in reproductive behavior.

Automated control of odor dynamics for neurophysiology and behavior

Animals use their olfactory systems to avoid predators, forage for food, and identify mates. Olfactory systems detect and distinguish odors by responding to the concentration, temporal dynamics, and identities of odorant molecules. Studying the temporal neural processing of odors carried in air has been difficult because of the inherent challenge in precisely controlling odorized airflows over time. Odorized airflows interact with surfaces and other air currents, leading to a complex transformation from the odorized airflow that is desired to the olfactory stimulus that is delivered. Here, we present a method that achieves precise and automated control of the amplitude, baseline, and temporal structure of olfactory stimuli. We use this technique to analyze the temporal processing of olfactory stimuli in the early olfactory circuits and navigational behavior of larval Drosophila. Precise odor control and calcium measurements in the axon terminal of an Olfactory Receptor Neuron (ORN-Or42b) revealed dynamic adaptation properties: as in vertebrate photoreceptor neurons, Or42b-ORNs display simultaneous gain-suppression and speedup of their neural response. Furthermore, we found that ORN sensitivity to changes in odor concentration decreases with odor background, but the sensitivity to odor contrast is invariant -- this causes odor-evoked ORN activity to follow the Weber-Fechner Law. Using precise olfactory stimulus control with freely-moving animals, we uncovered correlations between the temporal dynamics of larval navigation motor programs and the neural response dynamics of second-order olfactory neurons. The correspondence between neural and behavioral dynamics highlights the potential of precise odor temporal dynamics control in dissecting the sensorimotor circuits for olfactory behaviors.