Female mice exhibit a hardwired preference to investigate pheromones released by male conspecifics. The neural pathways that convey pheromonal inputs to brain regions controlling motivated behaviors remain largely unknown. One brain region known to process pheromonal information conveyed via main- and accessory olfactory bulb inputs is the Medial Amygdala (Me), a limbic structure comprised of anterior (MeA) and posterior (MeP) subdivisions. Electrolytic lesions of the MeP blocked the normal preference of estrous female mice to investigate urinary odors emitted from breeding as opposed to castrated males whereas lesions of either the MeA or MeP significantly reduced females' display of the receptive lordosis posture in response to male mounts. Quantitative analysis of synaptic puncta in the efferent projection targets of these two amygdaloid subregions, visualized using fluorescent anterograde tract tracing techniques, revealed that the MeA and MeP differentially innervate several forebrain regions. The medial olfactory tubercle (mOT; a component of the ventral striatum) receives dense monosynaptic input from the MeA and responds selectively to breeding male (but not female) soiled bedding volatiles, indexed by augmented FOS expression. Using injections of the retrograde tracer, cholera toxin B (CTb), neurons were identified in the MeA and ventral tegmental area (VTA) that projected to the mOT in female mice and which also co-expressed FOS after exposure to breeding male, but not female, soiled bedding/urinary volatiles. This suggests that the MeA and VTA convey opposite-sex (male) pheromonal information to the mOT. Bilateral dopaminergic lesions of the anteromedial VS (a region which includes the mOT) eliminated females' preference for breeding male vs. female urinary pheromones, suggesting that dopaminergic modulation in the VS is necessary for the display of these behaviors. Lastly, bilateral silencing of mOT neuronal firing by the activation of the inhibitory DREADD receptor, hM4Di, induced by intraperitoneal injection of its ligand (CNO), also disrupted females' preference to investigate urinary odors from breeding males; this deficit was reversed when saline was administered instead of CNO. The Me, VTA, and mOT are essential segments of a neural reward circuit that motivates estrous female mice to seek out male pheromones, thereby facilitating mate recognition and reproductive success.

abstract: Research has shown that the ability to smell is the most direct sense an individual can experience. With every breath a person takes, the brain recognizes thousands of molecules and makes connections with our memories to determine their composition. With the amount of research looking into how and why we smell, researchers still have little understanding of how the nose and brain process an aroma, and how emotional and physical behavior is impacted. This research focused on the affects smell has on a caregiver in a simulated Emergency Department setting located in the SimET of Banner Good Samaritan Medical Center in Phoenix, Arizona. The study asked each participant to care for a programmed mannequin, or "patient", while performing simple computer-based tasks, including memory and recall, multi-tasking, and mood-mapping to gauge physical and mental performance. Three different aromatic environments were then introduced through diffusion and indirect inhalation near the participants' task space: 1) a control (no smell), 2) an odor (simulated dirty feet), and 3) an aroma (one of four true essential oils plus a current odor-eliminating compound used in many U.S. Emergency Departments). This study was meant to produce a stressful environment by leading the caregiver to stay in constant movement throughout the study through timed tasks, uncooperative equipment, and a needy "patient". The goal of this research was to determine if smells, and of what form of pleasantness and repulsiveness, can have an effect on the physical and mental performance of emergency caregivers. Findings from this study indicated that the "odor eliminating" method currently used in typical Emergency Departments, coffee grounds, is more problematic than helpful, and the introduction of true essential oils may not only reduce stress, but increase efficiency and, in turn, job satisfaction. / Dissertation/Thesis / M.S.D. Design 2013

The purpose of this study was to determine if a relationship existed between olfactory preferences and sexual orientation in Heterosexual, Entire Life lesbian, and Adopted Lifestyle lesbian women. Research in the area of olfaction and sexual behavior was reviewed and, on the basis of the literature, it was hypothesized that Heterosexual women would prefer male odors, Entire Life lesbian women would prefer female odors, and Adopted Lifestyle lesbian women would prefer male odors more than Entire Life lesbians. The design involved having female subjects sniff male and female odors and indicate a preference for either the male or female odor. The odor samples were human apocrine gland secretions obtained by having odor donors wear gauze pads in their armpits. The odor collected on the pads was then stabilized through applications of alcohol and subsequent freezing.

The present study evaluated the effects of utilizing derived relational responding protocols to teach non-arbitrary frames of opposition, comparison and distinction to two children with autism across tactile, auditory, and olfactory sensory modalities. Both participants were successful in demonstrating accurate responding across all skill programs, which included the demonstration of transfers of stimulus function. The results for both participants suggest that the programs were effective in fostering skill acquisition among individuals with ASD using the relational frames of opposition, distinction, and comparison by utilizing stimuli with sensory qualities of tactile, olfactory, and auditory modalities respectively.

The mouse olfactory system detects odorants with 1000 olfactory receptors (ORs). Olfactory sensory neurons (OSNs) express only 1 OR. OSNs expressing a common OR converge on a single glomerulus, a stereotyped location in the olfactory bulb (OB). Thus, odorants are represented by a spatial map of glomerular activation. OB odor representations are then processed by five central brain regions. One region, cortical amygdala (CoA), receives spatially patterned and stereotyped axonal input from the OB and is both necessary and sufficient for innate behavioral responses to odor. However, CoA receives input from all glomeruli and forms a representation of every odor. It is not known why all odors are represented in CoA or how some odor representations elicit behavior while others do not. One hypothesis is that only rare neurons in CoA, not activated by most odors, participate in innate signaling. Another hypothesis is that all neurons in CoA participate in innate signaling, but for many odors, opposing CoA outputs cancel out downstream. These hypotheses were addressed by single nuclei sequencing and in situ hybridization which identified and localized neuronal cell types within CoA. Cell types are topographically segregated in regions well positioned to differentially receive inputs from genetically defined subsets of glomeruli. Therefore, the connectivity between OB and CoA may instantiate a genetically wired circuit from OB to cortex for innate odor processing. A number of rare and common cell types were identified. Thus, CoA may process two types of innate signals: (1) specific innate signals, produced by few glomeruli and processed by rare CoA cell types; (2) broad innate signals, produced by many glomeruli and processed by common CoA cell types through the integration of probabilistic information about the value of odorants.

L’infection virale des voies respiratoires supérieures est la cause la plus fréquente des troubles de l’odorat. L’entraînement olfactif permet un rétablissement des fonctions olfactives chez une bonne proportion des patients avec une perte olfactive post-virale. Aussi, les fonctions olfactives sont corrélées avec différentes mesures neuroanatomiques du cortex olfactif. L’objectif de ce mémoire est donc de reproduire les résultats bénéfiques de l’entraînement olfactif chez des patients avec un trouble de l’odorat post-viral et d’observer si le rétablissement des performances olfactives modifie l’épaisseur corticale des régions olfactives. Trente-neuf patients ayant un trouble de l’odorat post-viral ont complété un entraînement olfactif d’une durée de 12 semaines. L’entraînement olfactif consistait à sentir des contenants avec une odeur de rose, de citron, d’eucalyptus et de clou de girofle, deux fois par jour. Les capacités olfactives ont été mesurées avec les tests Sniffin’Sticks au début et à la fin de l’étude. L’entraînement olfactif a permis l’amélioration clinique (≥6 points SDI) des fonctions olfactives chez 59% des patients. Ces patients avaient une épaisseur corticale plus importante au niveau du cortex orbitofrontal latéral gauche à p<0,0001 non corrigé. Les patients avec une amélioration du score SDI (≥0,25 points) ont une augmentation de l’épaisseur du cortex orbitofrontal médial gauche, du cortex entorhinal droit et du cortex cingulaire postérieur gauche (p<0,0001, non corrigé). Ces résultats démontrent l’efficacité de l’entraînement olfactif chez les patients avec un trouble de l’odorat post-viral et que la rémission des fonctions olfactives semble modifier l’épaisseur corticale de certaines régions du cortex olfactif. / Viral infection of the upper respiratory tract is the most common cause of disturbances in smell. Olfactory training allows a reestablishment of olfactory functions in a good proportion of patients with post-viral olfactory loss. Also, olfactory functions are correlated with different neuroanatomic measures of the olfactory cortex. The objective of this dissertation is therefore to reproduce the beneficial results of olfactory training in patients with post-viral olfactory dysfunction and to observe whether the restoration of olfactory performances changes the cortical thickness of the olfactory cortex. Thirty-nine patients with post-viral olfactory dysfunction completed a twelve-week olfactory training. The olfactory training consisted of smelling containers with the scent of roses, lemon, eucalyptus and cloves, twice a day. Olfactory functions were measured with the Sniffin'Sticks tests at the start and end of the study. Olfactory training resulted in clinical improvement (≥6 SDI points) of olfactory functions in 59% of patients. These patients had greater cortical thickness in the left lateral orbitofrontal cortex at p <0,0001 uncorrected. Patients with improved SDI score (≥0,25 points) had an increase in the thickness of the left medial orbitofrontal cortex, right entorhinal cortex and left posterior cingulate cortex (p <0,0001, uncorrected). These results demonstrate the effectiveness of olfactory training in patients with post-viral olfactory loss and that remission of olfactory functions appears to alter the cortical thickness of certain regions of the olfactory cortex.

No description available.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13525号 / 論医博第2271号 / 新制||医||1062(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 大森 孝一, 教授 古川 壽亮 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Some of life’s most important behaviors are guided by the sense of smell. Detecting and interpreting odor information influences food-seeking, predator avoidance, sociality, competition, mating rituals, and more, shaping how organisms interact with their environment. In vertebrates, odors are detected by olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE). OSNs rely on olfactory receptors (ORs) to recognize odorants and trigger neural activation. The OR gene pool is typically vast, containing between 200-4000 olfactory receptor genes across mammals, yet mature OSNs stably express only one gene from one allele. Data from mice show that ORs are anatomically restricted to designated sections of the MOE, but within these zones, OR expression appears mosaic and random. Since the discovery of the OR gene pool 30 years ago, deciphering how OSNs choose which OR they are going to express remains a central question. While multiple differentiation-dependent alterations to the OSN nucleus are required for OR expression, the most notable contribution comes from the organization of OR-gene specific enhancers, called Greek Islands (GIs), around the chosen allele. GIs use the transcription factors Lhx2 and Ebf1, as well as the coactivator Ldb1, to form a nucleoprotein complex known as the Greek Island Hub (GIH) to associate with the active OR gene and support its transcription. Bulk Hi-C data show that GIs form strong, specific, and singular associations with the active OR gene, suggesting a possible role for the GIH in singular OR choice. However, single-cell Hi-C analysis shows that multiple GIHs exist in every OSN with no clear differences between them, complicating the contribution of the GIH. Furthermore, ectopic OR gene activation is sufficient to drive association of an OR locus with a GIH and bias choice, suggesting a role for OR transcription itself in supporting its own stable expression. To clarify the genomic transformations that result in the formation of multiple GIHs, I performed combined scRNA-seq and scATAC-seq in the MOE. I determined that a selective inactivation event was taking place during the INP3-to-iOSN transition, where OSNs would silence a large fraction of the GI pool. GI inactivation takes place during a phase preceding OR choice, where OR expression is polygenic but skewed towards one OR. My single-cell Hi-C analysis verifies the presence of multiple GIHs per cell, with similar GI-GI interaction properties, but I also observe that the single active GIH contains much more specific GI-OR gene interactions than those in inactive GIHs. These architectural differences are supported by Liquid Hi-C and H3K27ac HiChIP analysis where I observe that the active GIH is more highly acetylated than inactive GIHs and possesses more euchromatic physical properties. Taken together these data show that while most GIs were initially euchromatic during the polygenic phase of OR expression, once choice has taken place, GIHs possess distinct OR interaction properties, chromatin marks, and physical features that are determined by their association with the active OR gene. I believe that these data are best explained by a winner-takes-all event, where GIHs containing transcribed OR genes during the polygenic phase are in competition for choice. Once one OR begins to win, it recruits resources to maintain its expression which consequently results in the silencing of other GIHs. Ectopic induction of OR gene transcription is sufficient to bias choice and silence other ORs by impeding their specific association with a GIH. I find that this does not depend on the coding properties of OR protein, as the transcription of non-coding OR mRNAs still results in OR gene silencing. I describe this competition as a symmetry breaking process, where asymmetrical reorganization of transcriptional resources to a single GIH is mediated by non-coding properties of a single highly expressed OR mRNA, culminating in the stable expression of that allele alone for the remainder of a cell’s lifetime.

No description available.