The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice.

PubMed

Degl'Innocenti, Andrea; Parrilla, Marta; Harr, Bettina; Teschke, Meike

2016-01-01

In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice. Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice. Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections. In the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings favor Olfr266 as a model gene to investigate odorant receptor gene choice.

Baicalin Modulates APPL2/Glucocorticoid Receptor Signaling Cascade, Promotes Neurogenesis, and Attenuates Emotional and Olfactory Dysfunctions in Chronic Corticosterone-Induced Depression.

PubMed

Gao, Chong; Du, Qiaohui; Li, Wenting; Deng, Ruixia; Wang, Qi; Xu, Aimin; Shen, Jiangang

2018-04-19

Olfactory dysfunction is often accompanied with anxiety- and depressive-like behaviors in depressive patients. Impaired neurogenesis in hippocampus and subventricular zone (SVZ)-olfactory bulb (OB) contribute to anxiety- and depressive-like behaviors and olfactory dysfunctions. However, the underlying mechanisms of olfactory dysfunction remain unclear. Our previous study indicates that adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2), could affect the activity and sensitivity of glucocorticoid receptor (GR) and mediate impaired hippocampal neurogenesis, which contribute the development of depression. In the present study, we further identified the roles of APPL2 in olfactory functions. APPL2 Tg mice displayed higher GR activity and less capacity of neurogenesis at olfactory system with less olfactory sensitivity than WT mice, indicating that APPL2 could be a potential therapeutic target for depression and olfactory deficits. We then studied the effects of baicalin, a medicinal herbal compound, on modulating APPL2/GR signaling pathway for promoting neurogenesis and antidepressant as well as improving olfactory functions. Baicalin treatment inhibited APPL2/GR signaling pathway and improved neurogenesis at SVZ, OB, and hippocampus in APPL2 Tg mice and chronic corticosterone-induced depression mouse model. Behavioral tests revealed that baicalin attenuated depressive- and anxiety-like behaviors and improve olfactory functions in the chronic depression mouse model and APPL2 Tg mice. Taken together, APPL2 could be a novel therapeutic target for improving depressant-related olfactory dysfunctions and baicalin could inhibit APPL2-mediated GR hyperactivity and promote adult neurogenesis, subsequently releasing depressive and anxiety symptoms and improving olfactory functions for antidepressant therapy.

The nervus terminalis in the mouse: light and electron microscopic immunocytochemical studies.

PubMed

Jennes, L

1987-01-01

The distribution of gonadotropin-releasing hormone (GnRH)-containing neurons and fibers in the olfactory bulb was studied with light and electron microscopic immunohistochemistry in combination with retrograde transport of "True Blue" and horseradish peroxidase and lesion experiments. GnRH-positive neurons are found in the septal roots of the nervus terminalis, in the ganglion terminale, intrafascicularly throughout the nervus terminalis, in a dorso-ventral band in the caudal olfactory bulb, in various layers of the main and accessory olfactory bulb, and in the basal aspects of the nasal epithelium. Electron microscopic studies show that the nerve fibers in the nervus terminalis are not myelinated and are not surrounded by Schwann cell sheaths. In the ganglion terminale, "smooth" GnRH neurons are seen in juxtaposition to immunonegative neurons. Occasionally, axosomatic specializations are found in the ganglion terminale, but such synaptic contacts are not seen intrafascicularly in the nervus terminalis. Retrograde transport studies indicate that certain GnRH neurons in the septal roots of the nervus terminalis were linked to the amygdala. In addition, a subpopulation of nervus terminalis-related GnRH neurons has access to fenestrated capillaries whereas other GnRH neurons terminate at the nasal epithelium. Lesions of the nervus terminalis caudal to the ganglion terminale result in sprouting of GnRH fibers at both sites of the knife cut. The results suggest that GnRH in the olfactory system of the mouse can influence a variety of target sites either via the blood stream, via the external cerebrospinal fluid or via synaptic/asynaptic contacts with, for example, the receptor cells in the nasal mucosa.

Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb.

PubMed

Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E

2013-08-21

Animals modulate their courtship and territorial behaviors in response to olfactory cues produced by other animals. In rodents, detecting these cues is the primary role of the accessory olfactory system (AOS). We sought to systematically investigate the natural stimulus coding logic and robustness in neurons of the first two stages of accessory olfactory processing, the vomeronasal organ (VNO) and accessory olfactory bulb (AOB). We show that firing rate responses of just a few well-chosen mouse VNO or AOB neurons can be used to reliably encode both sex and strain of other mice from cues contained in urine. Additionally, we show that this population code can generalize to new concentrations of stimuli and appears to represent stimulus identity in terms of diverging paths in coding space. Together, the results indicate that firing rate code on the temporal order of seconds is sufficient for accurate classification of pheromonal patterns at different concentrations and may be used by AOS neural circuitry to discriminate among naturally occurring urine stimuli.

Olfactory regulation of the sexual behavior and reproductive physiology of the laboratory mouse: effects and neural mechanisms.

PubMed

Kelliher, Kevin R; Wersinger, Scott R

2009-01-01

In many species, chemical compounds emitted by conspecifics exert profound effects on reproductive physiology and sexual behavior. This is particularly true in the mouse, where such cues advance and delay puberty, suppress and facilitate estrous cycles, and cause the early termination of pregnancy. They also facilitate sexual behavior and inform mate selection. The mouse has a rich and complex repertoire of social behaviors. The technologies of molecular genetics are well developed in the mouse. Gene expression can be experimentally manipulated in the mouse relatively easily and in a time- and tissue-specific manner. Thus, the mouse is an excellent model in which to investigate the genetic, neural, and hormonal bases by which chemical compounds released by other mice affect physiology and behavior. These chemical cues are detected and processed by the olfactory system and other specialized but less well characterized sensory organs. The sensory information reaches brain regions that regulate hormone levels as well as those that are involved in behavior and alters the function of these brain regions. The effects of these chemical compounds have important implications for the laboratory animal facility as well as for researchers. We begin with an overview of the basic structure and function of the olfactory system and of the connections among brain regions that receive olfactory stimuli. We discuss the effects of chemosensory cues on the behavior and physiology of the organism along with what is known about the neural and hormonal mechanisms underlying these effects. We also describe some of the implications for the laboratory animal facility.

Effects of statins on the recovery of olfactory function in a 3-methylindole-induced anosmia mouse model.

PubMed

Kim, Hyo Yeol; Kim, Joon Ho; Dhong, Hun-Jong; Kim, Ki Ryung; Chung, Seung-Kyu; Chung, Soo-Chan; Kang, Jeong Min; Jung, Yong Gi; Jang, Seong Yun; Hong, Sang Duk

2012-01-01

Despite the importance of olfactory function, no effective medications have been identified to treat olfactory disorders. This study was performed to evaluate the functional recovery of olfaction damaged by 3-methylindole (3MI) in a mouse model with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins). In a randomized placebo-controlled trial, 24 healthy female BALB/c mice (aged 9-10 weeks and weighing 18-20 g each) were randomly allocated to statin-treated or control groups. Olfactory loss was induced by i.p. injections of 3MI. Atorvastatin (10 mg/kg) or normal saline was then administered per os with a gastric tube for 3 weeks. The effects of treatment were evaluated by food-finding tests and Western blot analysis. Both groups showed complete losses of olfactory function 1 week after 3MI injection. Three weeks after 3MI injection, 9 of the 12 mice in the statin-treated group (75%) passed a food-finding test, in which they were able to find the food within 3 minutes, at least two times out of three trials. However, only two mice in the control group (16.6%) passed the food-finding test, and this difference was statistically significant (p = 0.004; chi-square test). The expression level of the olfactory marker protein was also elevated in the statin-treated group (p = 0.030; Wilcoxon rank sum test). Statins are associated with recovery of olfaction after 3MI injection in a mouse model.

Development of a mouse test for repetitive, restricted behaviors: relevance to autism.

PubMed

Moy, Sheryl S; Nadler, Jessica J; Poe, Michele D; Nonneman, Randal J; Young, Nancy B; Koller, Beverly H; Crawley, Jacqueline N; Duncan, Gary E; Bodfish, James W

2008-03-17

Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently demonstrated for one particular olfactory stimulus. Further work is required to determine the characteristics of optimal mouse social stimuli in the olfactory hole-board test.

Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

PubMed

Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

2000-07-01

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

5HTR3A-driven GFP labels immature olfactory sensory neurons.

PubMed

Finger, Thomas E; Bartel, Dianna L; Shultz, Nicole; Goodson, Noah B; Greer, Charles A

2017-05-01

The ionotropic serotonin receptor, 5-HT 3 , is expressed by many developing neurons within the central nervous system. Since the olfactory epithelium continues to generate new olfactory sensory neurons (OSNs) throughout life, we investigated the possibility that 5-HT 3 is expressed in the adult epithelium. Using a transgenic mouse in which the promoter for the 5-HT 3a subunit drives expression of green fluorescent protein (GFP), we assessed the expression of this marker in the olfactory epithelium of adult mice. Both the native 5-HT 3a mRNA and GFP are expressed within globose basal cells of the olfactory and vomeronasal epithelium in adult mice. Whereas the 5-HT 3a mRNA disappears relatively quickly after final cell division, the GFP label persists for about 5 days, thereby labeling immature OSNs in both the main olfactory system and vomeronasal organ. The GFP-labeled cells include both proliferative globose basal cells as well as immature OSNs exhibiting the hallmarks of ongoing differentiation including GAP43, PGP9.5, but the absence of olfactory marker protein. Some of the GFP-labeled OSNs show characteristics of more mature yet still developing OSNs including the presence of cilia extending from the apical knob and expression of NaV1.5, a component of the transduction cascade. These findings suggest that 5-HT 3a is indicative of a proliferative or developmental state, regardless of age, and that the 5-HT 3A GFP mice may prove useful for future studies of neurogenesis in the olfactory epithelium. J. Comp. Neurol. 525:1743-1755, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Experimental evidence for olfactory predator recognition in wild mouse lemurs.

PubMed

Kappel, Philipp; Hohenbrink, Sarah; Radespiel, Ute

2011-09-01

Although primates have remarkable olfactory capabilities, their ability for olfactory predator recognition is still understudied. We investigated this cognitive ability in wild gray and golden-brown mouse lemurs (Microcebus murinus and M. ravelobensis) that were confronted with four different olfactory stimuli, derived from two Malagasy predators (fossa and barn owl) and two local nonpredator species (brown lemur and sifaka). The predator response was tested (1) in a systematic cage setup and (2) in a two-way choice experiment with two Sherman traps on platforms in the forest (stimulus trap vs. nonstimulus trap). For part 1, the study animals were housed in cages during habituation and 5 days of experiments. One stimulus was tested per night and was presented underneath a drinking bottle. The changes in the time spent close to the stimulus and the drinking time at the bottle were used as indicators of predator recognition. A timidity score was established by classifying the strength of the antipredator response during the experiment. The study animals spent significantly less time drinking and less time in the stimulus area when confronted with fossa odor compared with the other stimuli. The timidity score was significantly higher during the fossa stimulus compared with the nonpredator and the control stimuli. The two-way choice experiments revealed a complete avoidance of the fossa odor, which was not found with the other stimuli. Thus, wild mouse lemurs showed clear signs of olfactory predator recognition in the case of the fossa in both experiments, but no signs of avoidance to the other presented stimuli. The lack of owl avoidance may be explained by less or no aversive metabolites in the owl stimulus or by lower significance for olfactory recognition of aerial predators. Furthermore, the results showed slight differences between the two mouse lemur species that may be linked to differences in their ecology. © 2011 Wiley-Liss, Inc.

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice.

PubMed

Matsuo, Tomohiko; Hattori, Tatsuya; Asaba, Akari; Inoue, Naokazu; Kanomata, Nobuhiro; Kikusui, Takefumi; Kobayakawa, Reiko; Kobayakawa, Ko

2015-01-20

Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites

PubMed Central

LaRocca, Greg

2017-01-01

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. SIGNIFICANCE STATEMENT The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively. PMID:28003347

Social modulation of associative fear learning by pheromone communication

PubMed Central

Bredy, Timothy W.; Barad, Mark

2009-01-01

Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned familiar mouse and by the putative stress-related anxiogenic pheromone β-phenylethylamine (β-PEA). Together, these findings suggest social modulation of higher-order cognitive processing through pheromone communication and support the concurrent excitor hypothesis of extinction learning. PMID:19117912

Social modulation of associative fear learning by pheromone communication.

PubMed

Bredy, Timothy W; Barad, Mark

2009-01-01

Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned familiar mouse and by the putative stress-related anxiogenic pheromone beta-phenylethylamine (beta-PEA). Together, these findings suggest social modulation of higher-order cognitive processing through pheromone communication and support the concurrent excitor hypothesis of extinction learning.

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice

PubMed Central

Degl'Innocenti, Andrea

2016-01-01

Background In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice. Aim Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice. Procedures Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections. Results In the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings favor Olfr266 as a model gene to investigate odorant receptor gene choice. PMID:26794459

Effect of ginkgo biloba and dexamethasone in the treatment of 3-methylindole-induced anosmia mouse model.

PubMed

Lee, Chul Hee; Mo, Ji-Hun; Shim, Seung Hee; Ahn, Jung-Min; Kim, Jeong-Whun

2008-01-01

Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.

MouSensor: A Versatile Genetic Platform to Create Super Sniffer Mice for Studying Human Odor Coding.

PubMed

D'Hulst, Charlotte; Mina, Raena B; Gershon, Zachary; Jamet, Sophie; Cerullo, Antonio; Tomoiaga, Delia; Bai, Li; Belluscio, Leonardo; Rogers, Matthew E; Sirotin, Yevgeniy; Feinstein, Paul

2016-07-26

Typically, ∼0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these "MouSensors." In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 MouSensor. Moreover, a behavioral avoidance task demonstrates that specific odor detection thresholds are significantly decreased in multiple transgenic lines, expressing mouse or human ORs. We have developed a versatile platform to study gene choice and axon identity, to create biosensors with great translational potential, and to finally decode human olfaction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Social Modulation of Associative Fear Learning by Pheromone Communication

ERIC Educational Resources Information Center

Bredy, Timothy W.; Barad, Mark

2009-01-01

Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned…

Olfactory epithelium influences the orientation of mitral cell dendrites during development.

PubMed

López-Mascaraque, Laura; García, Concepción; Blanchart, Albert; De Carlos, Juan A

2005-02-01

We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Copyright 2004 Wiley-Liss, Inc.

Methods to measure olfactory behavior in mice

PubMed Central

Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Lu, Song; Xia, Zhengui

2015-01-01

Mice rely on the sense of olfaction to detect food sources, recognize social and mating partners, and avoid predators. Many behaviors of mice including learning and memory, social interaction, fear, and anxiety are closely associated with their function of olfaction, and behavior tasks designed to evaluate those brain functions may use odors as cues. Accurate assessment of olfaction is not only essential for the study of olfactory system but also critical for proper interpretation of various mouse behaviors especially learning and memory, emotionality and affect, and sociality. Here we describe a series of behavior experiments that offer multidimensional and quantitative assessments for mouse’s olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, to both social and nonsocial odors. PMID:25645244

Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

PubMed

Shiga, Hideaki; Nagaoka, Mikiya; Washiyama, Kohshin; Yamamoto, Junpei; Yamada, Kentaro; Noda, Takuya; Harita, Masayuki; Amano, Ryohei; Miwa, Takaki

2014-09-01

Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mammalian social odours: attraction and individual recognition

PubMed Central

Brennan, Peter A; Kendrick, Keith M

2006-01-01

Mammalian social systems rely on signals passed between individuals conveying information including sex, reproductive status, individual identity, ownership, competitive ability and health status. Many of these signals take the form of complex mixtures of molecules sensed by chemosensory systems and have important influences on a variety of behaviours that are vital for reproductive success, such as parent–offspring attachment, mate choice and territorial marking. This article aims to review the nature of these chemosensory cues and the neural pathways mediating their physiological and behavioural effects. Despite the complexities of mammalian societies, there are instances where single molecules can act as classical pheromones attracting interest and approach behaviour. Chemosignals with relatively high volatility can be used to signal at a distance and are sensed by the main olfactory system. Most mammals also possess a vomeronasal system, which is specialized to detect relatively non-volatile chemosensory cues following direct contact. Single attractant molecules are sensed by highly specific receptors using a labelled line pathway. These act alongside more complex mixtures of signals that are required to signal individual identity. There are multiple sources of such individuality chemosignals, based on the highly polymorphic genes of the major histocompatibility complex (MHC) or lipocalins such as the mouse major urinary proteins. The individual profile of volatile components that make up an individual odour signature can be sensed by the main olfactory system, as the pattern of activity across an array of broadly tuned receptor types. In addition, the vomeronasal system can respond highly selectively to non-volatile peptide ligands associated with the MHC, acting at the V2r class of vomeronasal receptor. The ability to recognize individuals or their genetic relatedness plays an important role in mammalian social behaviour. Thus robust systems for olfactory learning and recognition of chemosensory individuality have evolved, often associated with major life events, such as mating, parturition or neonatal development. These forms of learning share common features, such as increased noradrenaline evoked by somatosensory stimulation, which results in neural changes at the level of the olfactory bulb. In the main olfactory bulb, these changes are likely to refine the pattern of activity in response to the learned odour, enhancing its discrimination from those of similar odours. In the accessory olfactory bulb, memory formation is hypothesized to involve a selective inhibition, which disrupts the transmission of the learned chemosignal from the mating male. Information from the main olfactory and vomeronasal systems is integrated at the level of the corticomedial amygdala, which forms the most important pathway by which social odours mediate their behavioural and physiological effects. Recent evidence suggests that this region may also play an important role in the learning and recognition of social chemosignals. PMID:17118924

High convergence of olfactory and vomeronasal influence in the telencephalon of the terrestrial salamander Plethodon shermani.

PubMed

Roth, F C; Laberge, F

2011-03-17

Previous work suggested that the telencephalic pathways of the main olfactory and vomeronasal systems of vertebrates are mostly isolated from each other, with the possible exception of convergence of the two systems into a small part of the olfactory amygdala. We tested the hypothesis of convergence between the main olfactory and vomeronasal systems by investigating the physiology of telencephalic olfactory responses in an in vitro brain preparation of the salamander Plethodon shermani. This animal was chosen because its olfactory and vomeronasal nerves can be separated and stimulated independently. The nerves were stimulated by short current pulses delivered through suction electrodes. Evoked field potentials and intracellular responses were systematically recorded in the telencephalon. The results showed an abundant overlap of olfactory and vomeronasal nerve-evoked field potentials in the ipsilateral lateral telencephalon and the amygdala. Single neurons receiving bimodal main olfactory and vomeronasal input were found in the dorsolateral telencephalon and amygdala. A classification of response latencies suggested that a subset of these neurons received direct input from both the main and accessory olfactory bulbs. Unimodal excitatory main olfactory responses were mostly found in neurons of the caudal telencephalic pole, but were also present in the striato-pallial transition area/lateral pallium region and striatum. Unimodal excitatory vomeronasal responses were found in neurons of the striato-pallial transition area, vomeronasal amygdala, and caudal amygdala. We conclude that the main olfactory and vomeronasal systems are extensively integrated within the salamander telencephalon and probably act in concert to modulate behavior. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

The Accessory Olfactory System Facilitates the Recovery of the Attraction to Familiar Volatile Female Odors in Male Mice.

PubMed

Muroi, Yoshikage; Nishimura, Masakazu; Ishii, Toshiaki

2017-10-31

Odors in female mice induce sexual arousal in male mice. Repeated exposure to female odors attenuates male attraction, which recovers when the odors are removed. The neuronal mechanisms for the recovery of male attraction have not been clarified. In this study, we examined how olfactory systems are involved in the recovery of male attraction to female odors following habituation in mice. Presentation with volatile female odors for 5 min induced habituation in males. To evaluate male attraction to familiar volatile female odors, we measured the duration for investigating volatile female odors from the same female mouse, which was presented twice for 5 min with 1-, 3-, or 5-min interval. Intranasal irrigation with ZnSO4 solution almost completely suppressed investigating behavior, indicating that the main olfactory system is indispensable for inducing the attraction to volatile female odors. In contrast, removal of the vomeronasal organ, bilateral lesions of the accessory olfactory bulb (AOB), or pharmacological blockage of neurotransmission in the AOB did not affect the investigation time at the first odor presentation. However, each one of the treatments decreased the investigation time in the second presentation, compared to that in the first presentation, at longer intervals than control treatment, indicating that the disturbance of neurotransmission in the accessory olfactory system delayed the recovery of the attraction attenuated by the first presentation. These results suggest that the accessory olfactory system facilitates the recovery of the attraction to familiar volatile female odors in male mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacological and immunochemical characterization of α2* nicotinic acetylcholine receptors (nAChRs) in mouse brain

PubMed Central

Whiteaker, Paul; Wilking, Jennifer A; Brown, Robert WB; Brennan, Robert J; Collins, Allan C; Lindstrom, Jon M; Boulter, Jim

2009-01-01

Aim: α2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of α2* nAChRs in these mouse brain regions. Methods: α2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were used to determine the composition of α2 subunit-containing (α2*) nAChRs in these two regions. Results: [125I]Epibatidine (200 pmol/L) autoradiography and saturation binding demonstrated that α2 deletion reduces nAChR expression in both olfactory bulbs and interpeduncular nucleus (by 4.8±1.7 and 92±26 fmol̇mg-1 protein, respectively). Pharmacological characterization using the β2-selective drug A85380 to inhibit [125I]epibatidine binding proved inconclusive, so immunoprecipitation methods were used to further characterize α2* nAChRs. Protocols were established to immunoprecipitate β2 and β4 nAChRs. Immunoprecipitation specificity was ascertained using tissue from β2- and β4-null mutant mice, and efficacy was good (>90% of β2* and >80% of β4* nAChRs were routinely recovered). Conclusion: Immunoprecipitation experiments indicated that interpeduncular nucleus α2* nAChRs predominantly contain β2 subunits, while those in olfactory bulbs contain mainly β4 subunits. In addition, the immunoprecipitation evidence indicated that both nuclei, but especially the interpeduncular nucleus, express nAChR complexes containing both β2 and β4 subunits. PMID:19498420

Olfactory marker protein is critical for functional maturation of olfactory sensory neurons and development of mother preference

PubMed Central

Lee, Anderson C.; He, Jiwei; Ma, Minghong

2011-01-01

Survival of many altricial animals critically depends on the sense of smell. Curiously, the olfactory system is rather immature at birth and undergoes a maturation process, which is poorly understood. Using patch clamp technique on mouse olfactory sensory neurons (OSNs) with a defined odorant receptor (OR), we demonstrate that OSNs exhibit functional maturation during the first month of postnatal life by developing faster response kinetics, higher sensitivity, and most intriguingly, higher selectivity. OSNs expressing the receptor MOR23 are relatively broadly tuned in neonates and become selective detectors for the cognate odorant within two weeks. Remarkably, these changes are prevented by genetic ablation of olfactory marker protein (OMP), which is exclusively expressed in mature OSNs. Biochemical and pharmacological evidence supports that alteration in odorant-induced phosphorylation of signaling proteins underlie some of the OMP−/− phenotypes. Furthermore, in a novel behavioral assay in which the mouse pups are given a choice between the biological mother and another unfamiliar lactating female, wild-type pups prefer the biological mother, while OMP knockout pups fail to show preference. These results reveal that OSNs undergo an OMP-dependant functional maturation process that coincides with early development of the smell function, which is essential for pups to form preference for their mother. PMID:21414919

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.

PubMed

Rey, Nolwen L; Jardanhazi-Kurutz, Daniel; Terwel, Dick; Kummer, Markus P; Jourdan, Francois; Didier, Anne; Heneka, Michael T

2012-02-01

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model.

PubMed

Wesson, Daniel W; Levy, Efrat; Nixon, Ralph A; Wilson, Donald A

2010-01-13

Alzheimer's disease often results in impaired olfactory perceptual acuity-a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-beta (Abeta) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-beta precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically-some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar Abeta deposition within the olfactory bulb-earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of Abeta deposition. Therefore, nonfibrillar, versus fibrillar, Abeta-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites.

PubMed

Burton, Shawn D; LaRocca, Greg; Liu, Annie; Cheetham, Claire E J; Urban, Nathaniel N

2017-02-01

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively. Copyright © 2017 the authors 0270-6474/17/371117-22$15.00/0.

Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23.

PubMed

Lam, Rebecca S; Mombaerts, Peter

2013-07-01

The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The olfactory gonadotropin-releasing hormone immunoreactive system in mouse.

PubMed

Jennes, L

1986-10-29

The olfactory gonadotropin-releasing hormone (GnRH) system in mice was studied with immunofluorescence in combination with lesions of the olfactory bulb and retrograde transport of horseradish peroxidase (HRP) which was administered intravascularly, intranasally or into the subarachnoid space. GnRH-positive neurons were located in the two major branches forming the septal roots of the nervus terminalis, in the ganglion terminale, within the fascicles of the nervus terminalis throughout its extent, in a conspicuous band which connects the ventral neck of the caudal olfactory bulb with the accessory olfactory bulb and in the nasal mucosa. GnRH-positive fibers were seen in all areas in which neurons were found, i.e. in the rostral septum, the ganglion and nervus terminalis and in the nasal subepithelium. In addition, a broad bundle of fibers was observed to surround the entire caudal olfactory bulb, connecting the rostral sulcus rhinalis with the ventrocaudal olfactory bulb. Fibers were seen in close association with the main and accessory olfactory bulb, with the fila olfactoria and with the nasal mucosa. Throughout the olfactory bulb and the nasal epithelium, an association of GnRH fibers with blood vessels was apparent. Intravascular and intranasal injection of HRP resulted in labeling of certain GnRH neurons in the septal roots of the nervus terminalis, the ganglion terminale, the nervus terminalis, the caudal ventrodorsal connection and in the accessory olfactory bulb. After placement of HRP into the subarachnoid space dorsal to the accessory olfactory bulb, about 50% of the GnRH neurons in the accessory olfactory bulb and in the ventrodorsal connection were labeled with HRP. Also, a few GnRH neurons in the rostral septum, the ganglion terminale and in the fascicles of the nervus terminalis had taken up the enzyme. Lesions of the nervus terminalis caudal to the ganglion terminale resulted in sprouting of GnRH fibers at both sites of the knife cut. Lesions rostral to the ganglion terminale induced sprouting mostly at the distal site of the knife cut while most but not all GnRH fibers proximal to the lesion had disappeared. The results of the present study indicate that the olfactory GnRH system is mostly associated with the nervus terminalis. This cranial nerve apparently projects to the central nervous system as well as the periphery. The results of the HRP uptake studies suggest that the GnRH neurons in the nervus terminalis have access to fenestrated capillaries in the subepithelial connective tissue of the nasal mucosa, to the nasal epithelium proper, and to the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS)

RhoE deficiency alters postnatal subventricular zone development and the number of calbindin-expressing neurons in the olfactory bulb of mouse.

PubMed

Ballester-Lurbe, Begoña; González-Granero, Susana; Mocholí, Enric; Poch, Enric; García-Manzanares, María; Dierssen, Mara; Pérez-Roger, Ignacio; García-Verdugo, José M; Guasch, Rosa M; Terrado, José

2015-11-01

The subventricular zone represents an important reservoir of progenitor cells in the adult brain. Cells from the subventricular zone migrate along the rostral migratory stream and reach the olfactory bulb, where they originate different types of interneurons. In this work, we have analyzed the role of the small GTPase RhoE/Rnd3 in subventricular zone cell development using mice-lacking RhoE expression. Our results show that RhoE null mice display a remarkable postnatal broadening of the subventricular zone and caudal rostral migratory stream. This broadening was caused by an increase in progenitor proliferation, observed in the second postnatal week but not before, and by an altered migration of the cells, which appeared in disorganized cell arrangements that impaired the appropriate contact between cells in the rostral migratory stream. In addition, the thickness of the granule cell layer in the olfactory bulb was reduced, although the density of granule cells did not differ between wild-type and RhoE null mice. Finally, the lack of RhoE expression affected the olfactory glomeruli inducing a severe reduction of calbindin-expressing interneurons in the periglomerular layer. This was already evident in the newborns and even more pronounced 15 days later when RhoE null mice displayed 89% less cells than control mice. Our results indicate that RhoE has pleiotropic functions on subventricular cells because of its role in proliferation and tangential migration, affecting mainly the development of calbindin-expressing cells in the olfactory bulb.

The development of the olfactory organs in newly hatched monotremes and neonate marsupials

PubMed Central

Schneider, Nanette Yvette

2011-01-01

Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the marsupial tammar wallaby, rabbits, rats and other eutherians. PMID:21592102

Cholinergic modulation of dopaminergic neurons in the mouse olfactory bulb.

PubMed

Pignatelli, Angela; Belluzzi, Ottorino

2008-04-01

Considerable evidence exists for an extrinsic cholinergic influence in the maturation and function of the main olfactory bulb. In this study, we addressed the muscarinic modulation of dopaminergic neurons in this structure. We used different patch-clamp techniques to characterize the diverse roles of muscarinic agonists on identified dopaminergic neurons in a transgenic animal model expressing a reporter protein (green fluorescent protein) under the tyrosine hydroxylase promoter. Bath application of acetylcholine (1 mM) in slices and in enzymatically dissociated cells reduced the spontaneous firing of dopaminergic neurons recorded in cell-attached mode. In whole-cell configuration no effect of the agonist was observed, unless using the perforated patch technique, thus suggesting the involvement of a diffusible second messenger. The effect was mediated by metabotropic receptors as it was blocked by atropine and mimicked by the m2 agonist oxotremorine (10 muM). The reduction of periglomerular cell firing by muscarinic activation results from a membrane-potential hyperpolarization caused by activation of a potassium conductance. This modulation of dopaminergic interneurons may be important in the processing of sensory information and may be relevant to understand the mechanisms underlying the olfactory dysfunctions occurring in neurodegenerative diseases affecting the dopaminergic and/or cholinergic systems.

Co-localization of TRPV2 and insulin-like growth factor-I receptor in olfactory neurons in adult and fetal mouse.

PubMed

Matsui, Hitoshi; Noguchi, Tomohiro; Takakusaki, Kaoru; Kashiwayanagi, Makoto

2014-01-01

TRPV2, a member of the transient receptor potential family, has been isolated as a capsaicin-receptor homolog and is thought to respond to noxious heat. Here we show that TRPV2 mRNA is predominantly expressed in the subpopulation of olfactory sensory neurons (OSNs). We carried out histochemical analyses of TRPV2 and insulin-like growth factor-I receptor (IGF-IR) using in situ hybridization and immunofluorescence in the adult olfactory system. In olfactory mucosa, intensive TRPV2 immunostaining was observed at the olfactory axon bundles but not at the soma. TRPV2-positive labeling was preferentially found in the olfactory nerve layer in the olfactory bulb (OB). Furthermore, we demonstrated that a positive signal for IGF-IR mRNA was detected in OSNs expressing TRPV2 mRNA. In embryonic stages, TRPV2 immunoreactivity was observed on axon bundles of developing OSNs in the nasal region starting from 12.5 d of gestation and through fetal development. Observations in this study suggest that TRPV2 coupled with IGF-IR localizes to growing olfactory axons in the OSNs.

Odor Coding by a Mammalian Receptor Repertoire

PubMed Central

Saito, Harumi; Chi, Qiuyi; Zhuang, Hanyi; Matsunami, Hiro; Mainland, Joel D.

2009-01-01

Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of over 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and unraveling mammalian odor coding. PMID:19261596

Activation of β-noradrenergic receptors enhances rhythmic bursting in mouse olfactory bulb external tufted cells.

PubMed

Zhou, Fu-Wen; Dong, Hong-Wei; Ennis, Matthew

2016-12-01

The main olfactory bulb (MOB) receives a rich noradrenergic innervation from the nucleus locus coeruleus. Despite the well-documented role of norepinephrine and β-adrenergic receptors in neonatal odor preference learning, identified cellular physiological actions of β-receptors in the MOB have remained elusive. β-Receptors are expressed at relatively high levels in the MOB glomeruli, the location of external tufted (ET) cells that exert an excitatory drive on mitral and other cell types. The present study investigated the effects of β-receptor activation on the excitability of ET cells with patch-clamp electrophysiology in mature mouse MOB slices. Isoproterenol and selective β 2 -, but not β 1 -, receptor agonists were found to enhance two key intrinsic currents involved in ET burst initiation: persistent sodium (I NaP ) and hyperpolarization-activated inward (I h ) currents. Together, the positive modulation of these currents increased the frequency and strength of ET cell rhythmic bursting. Rodent sniff frequency and locus coeruleus neuronal firing increase in response to novel stimuli or environments. The increase in ET excitability by β-receptor activation may better enable ET cell rhythmic bursting, and hence glomerular network activity, to pace faster sniff rates during heightened norepinephrine release associated with arousal. Copyright © 2016 the American Physiological Society.

Prominent facilitation at beta and gamma frequency range revealed with physiological calcium concentration in adult mouse piriform cortex in vitro

PubMed Central

Gleizes, Marie; Perrier, Simon P.; Fonta, Caroline

2017-01-01

Neuronal activity is characterized by a diversity of oscillatory phenomena that are associated with multiple behavioral and cognitive processes, yet the functional consequences of these oscillations are not fully understood. Our aim was to determine whether and how these different oscillatory activities affect short-term synaptic plasticity (STP), using the olfactory system as a model. In response to odorant stimuli, the olfactory bulb displays a slow breathing rhythm as well as beta and gamma oscillations. Since the firing of olfactory bulb projecting neurons is phase-locked with beta and gamma oscillations, structures downstream from the olfactory bulb should be driven preferentially at these frequencies. We examined STP exhibited by olfactory bulb inputs in slices of adult mouse piriform cortex maintained in vitro in an in vivo-like ACSF (calcium concentration: 1.1 mM). We replaced the presynaptic neuronal firing rate by repeated electrical stimulation (frequency between 3.125 and 100 Hz) applied to the lateral olfactory tract. Our results revealed a considerable enhancement of postsynaptic response amplitude for stimulation frequencies in the beta and gamma range. A phenomenological model of STP fitted to the data suggests that the experimental results can be explained by the interplay between three mechanisms: a short-term facilitation mechanism (time constant ≈160 msec), and two short-term depression mechanisms (recovery time constants <20 msec and ≈140 msec). Increasing calcium concentration (2.2 mM) resulted in an increase in the time constant of facilitation and in a strengthening of the slowest depression mechanism. As a result, response enhancement was reduced and its peak shifted toward the low beta and alpha ranges while depression became predominant in the gamma band. Using environmental conditions corresponding to those that prevail in vivo, our study shows that STP in the lateral olfactory tract to layer Ia synapse allows amplification of olfactory bulb inputs at beta and gamma frequencies. PMID:28820903

Experience-dependent olfactory behaviors of the parasitic nematode Heligmosomoides polygyrus

PubMed Central

Castelletto, Michelle L.; Gang, Spencer S.

2017-01-01

Parasitic nematodes of humans and livestock cause extensive disease and economic loss worldwide. Many parasitic nematodes infect hosts as third-stage larvae, called iL3s. iL3s vary in their infection route: some infect by skin penetration, others by passive ingestion. Skin-penetrating iL3s actively search for hosts using host-emitted olfactory cues, but the extent to which passively ingested iL3s respond to olfactory cues was largely unknown. Here, we examined the olfactory behaviors of the passively ingested murine gastrointestinal parasite Heligmosomoides polygyrus. H. polygyrus iL3s were thought to reside primarily on mouse feces, and infect when mice consume feces containing iL3s. However, iL3s can also adhere to mouse fur and infect orally during grooming. Here, we show that H. polygyrus iL3s are highly active and show robust attraction to host feces. Despite their attraction to feces, many iL3s migrate off feces to engage in environmental navigation. In addition, H. polygyrus iL3s are attracted to mammalian skin odorants, suggesting that they migrate toward hosts. The olfactory preferences of H. polygyrus are flexible: some odorants are repulsive for iL3s maintained on feces but attractive for iL3s maintained off feces. Experience-dependent modulation of olfactory behavior occurs over the course of days and is mediated by environmental carbon dioxide (CO2) levels. Similar experience-dependent olfactory plasticity occurs in the passively ingested ruminant-parasitic nematode Haemonchus contortus, a major veterinary parasite. Our results suggest that passively ingested iL3s migrate off their original fecal source and actively navigate toward hosts or new host fecal sources using olfactory cues. Olfactory plasticity may be a mechanism that enables iL3s to switch from dispersal behavior to host-seeking behavior. Together, our results demonstrate that passively ingested nematodes do not remain inactive waiting to be swallowed, but rather display complex sensory-driven behaviors to position themselves for host ingestion. Disrupting these behaviors may be a new avenue for preventing infections. PMID:29190282

Results of examination of the nasal mucosa. [in Apollo 17 BIOCORE pocket mice

NASA Technical Reports Server (NTRS)

Kraft, L. M.; Vogel, F. S.; Lloyd, B.; Benton, E. V.; Cruty, M. R.; Haymaker, W.; Leon, H. A.; Billingham, J.; Turnbill, C. E.; Teas, V.

1975-01-01

The olfactory epithelium, but not the nasal respiratory epithelium, of the four pocket mice (Perognathus longimembris) that survived their flight on Apollo XVII showed both diffuse alterations and numerous disseminated focal lesions. The olfactory mucosa of the mouse that died during flight was also affected, but to a minor degree insofar as could be determined. All this was in contrast to the normal appearance of the olfactory mucosa of the numerous control animals. A number of possible causes were considered: systemic or regional infection; inhaled particulate material (seed dust); by-products from the KO2 bed in aerosol or particulate form; gas contaminants originating in the flight package; volatile substances from the dead mouse; weightlessness; and cosmic ray particle radiation. Where feasible, studies were conducted in an effort to rule in or rule out some of these potentially causative factors. No definitive conclusions were reached as to the cause of the lesions in the flight mice.

Cooperative interactions enable singular olfactory receptor expression in mouse olfactory neurons

PubMed Central

Monahan, Kevin; Schieren, Ira; Cheung, Jonah; Mumbey-Wafula, Alice; Monuki, Edwin S

2017-01-01

The monogenic and monoallelic expression of only one out of >1000 mouse olfactory receptor (ORs) genes requires the formation of large heterochromatic chromatin domains that sequester the OR gene clusters. Within these domains, intergenic transcriptional enhancers evade heterochromatic silencing and converge into interchromosomal hubs that assemble over the transcriptionally active OR. The significance of this nuclear organization in OR choice remains elusive. Here, we show that transcription factors Lhx2 and Ebf specify OR enhancers by binding in a functionally cooperative fashion to stereotypically spaced motifs that defy heterochromatin. Specific displacement of Lhx2 and Ebf from OR enhancers resulted in pervasive, long-range, and trans downregulation of OR transcription, whereas pre-assembly of a multi-enhancer hub increased the frequency of OR choice in cis. Our data provide genetic support for the requirement and sufficiency of interchromosomal interactions in singular OR choice and generate general regulatory principles for stochastic, mutually exclusive gene expression programs. PMID:28933695

Functional organization of glomerular maps in the mouse accessory olfactory bulb

PubMed Central

Hammen, Gary F.; Turaga, Diwakar; Holy, Timothy E.; Meeks, Julian P.

2014-01-01

Summary The mammalian accessory olfactory system (AOS) extracts information about species, sex, and individual identity from social odors, but its functional organization remains unclear. We imaged presynaptic Ca2+ signals in vomeronasal inputs to the accessory olfactory bulb (AOB) during peripheral stimulation using light sheet microscopy. Urine- and steroid-responsive glomeruli densely innervated the anterior AOB. Glomerular activity maps for sexually mature female mouse urine overlapped maps for juvenile and/or gonadectomized urine of both sexes, whereas maps for sexually mature male urine were highly distinct. Further spatial analysis revealed a complicated organization involving selective juxtaposition and dispersal of functionally-grouped glomerular classes. Glomeruli that were similarly tuned to urines were often closely associated, whereas more disparately tuned glomeruli were selectively dispersed. Maps to a panel of sulfated steroid odorants identified tightly-juxtaposed groups that were disparately tuned and dispersed groups that were similarly tuned. These results reveal a modular, non-chemotopic spatial organization in the AOB. PMID:24880215

Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse.

PubMed

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2017-09-01

The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli. © 2017 Wiley Periodicals, Inc.

Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells

PubMed Central

Ogura, Tatsuya; Szebenyi, Steven A.; Krosnowski, Kurt; Sathyanesan, Aaron; Jackson, Jacqueline

2011-01-01

The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium. PMID:21676931

Non-motor parkinsonian pathology in aging A53T α-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function.

PubMed

Farrell, Kaitlin F; Krishnamachari, Sesha; Villanueva, Ernesto; Lou, Haiyan; Alerte, Tshianda N M; Peet, Eloise; Drolet, Robert E; Perez, Ruth G

2014-02-01

Aging, the main risk factor for Parkinson's disease (PD), is associated with increased α-synuclein levels in substantia nigra pars compacta (SNc). Excess α-synuclein spurs Lewy-like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α-synuclein for behavior and α-synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α-synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α-synuclein. Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α-synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α-synuclein pathology associated with pre-motor stages of PD. © 2013 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

PubMed Central

Arenkiel, Benjamin R.; Hasegawa, Hiroshi; Yi, Jason J.; Larsen, Rylan S.; Wallace, Michael L.; Philpot, Benjamin D.; Wang, Fan; Ehlers, Michael D.

2011-01-01

The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits. PMID:22216277

Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid.

PubMed

Roullet, F I; Wollaston, L; Decatanzaro, D; Foster, J A

2010-10-13

Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development. In humans, prenatal exposure to VPA can induce fetal valproate syndrome, which has been associated with autism. The present study examined mouse pups exposed in utero to VPA, measuring physical development, olfactory discrimination, and social behavior as well as expression of plasticity-related genes, brain derived neurotrophic factor (BDNF) and NMDA receptor subunits NR2A and NR2B. VPA-exposed mice showed delayed physical development, impaired olfactory discrimination, and dysfunctional pre-weaning social behavior. In situ hybridization experiments revealed lower cortical expression of BDNF mRNA in VPA animals. These results support the validity of the VPA mouse model for human autism and suggest that alterations in plasticity-related genes may contribute to the behavioral phenotype. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility.

PubMed

Fukuda, Nanaho; Yomogida, Kentaro; Okabe, Masaru; Touhara, Kazushige

2004-11-15

Although a subset of the olfactory receptor (OR) gene family is expressed in testis, neither their developmental profile nor their physiological functions have been fully characterized. Here, we show that MOR23 (a mouse OR expressed in the olfactory epithelium and testis) functions as a chemosensing receptor in mouse germ cells. In situ hybridization showed that MOR23 was expressed in round spermatids during stages VI-VIII of spermatogenesis. Lyral, a cognate ligand of MOR23, caused an increase in intracellular Ca2+ in a fraction of spermatogenic cells and spermatozoa. We also generated transgenic mice that express high levels of MOR23 in the testis and examined the response of their germ cells to lyral. The results provided evidence that lyral-induced Ca2+ increases were indeed mediated by MOR23. In a sperm accumulation assay, spermatozoa migrated towards an increasing gradient of lyral. Tracking and sperm flagellar analyses suggest that Ca2+ increases caused by MOR23 activation lead to modulation of flagellar configuration, resulting in chemotaxis. By contrast, a gradient of a cAMP analog or K8.6 solution, which elicit Ca2+ influx in spermatozoa, did not cause sperm accumulation, indicating that chemosensing and regulation of sperm motility was due to an OR-mediated local Ca2+ increase. The present studies indicate that mouse testicular ORs might play a role in chemoreception during sperm-egg communication and thereby regulate fertilization.

Detection and avoidance of a carnivore odor by prey

PubMed Central

Ferrero, David M.; Lemon, Jamie K.; Fluegge, Daniela; Pashkovski, Stan L.; Korzan, Wayne J.; Datta, Sandeep Robert; Spehr, Marc; Fendt, Markus; Liberles, Stephen D.

2011-01-01

Predator–prey relationships provide a classic paradigm for the study of innate animal behavior. Odors from carnivores elicit stereotyped fear and avoidance responses in rodents, although sensory mechanisms involved are largely unknown. Here, we identified a chemical produced by predators that activates a mouse olfactory receptor and produces an innate behavioral response. We purified this predator cue from bobcat urine and identified it to be a biogenic amine, 2-phenylethylamine. Quantitative HPLC analysis across 38 mammalian species indicates enriched 2-phenylethylamine production by numerous carnivores, with some producing >3,000-fold more than herbivores examined. Calcium imaging of neuronal responses in mouse olfactory tissue slices identified dispersed carnivore odor-selective sensory neurons that also responded to 2-phenylethylamine. Two prey species, rat and mouse, avoid a 2-phenylethylamine odor source, and loss-of-function studies involving enzymatic depletion of 2-phenylethylamine from a carnivore odor indicate it to be required for full avoidance behavior. Thus, rodent olfactory sensory neurons and chemosensory receptors have the capacity for recognizing interspecies odors. One such cue, carnivore-derived 2-phenylethylamine, is a key component of a predator odor blend that triggers hard-wired aversion circuits in the rodent brain. These data show how a single, volatile chemical detected in the environment can drive an elaborate danger-associated behavioral response in mammals. PMID:21690383

Postnatal Experience Modulates Functional Properties of Mouse Olfactory Sensory Neurons

PubMed Central

He, Jiwei; Tian, Huikai; Lee, Anderson C.; Ma, Minghong

2012-01-01

Early experience considerably modulates the organization and function of all sensory systems. In the mammalian olfactory system, deprivation of the sensory inputs via neonatal, unilateral naris closure has been shown to induce structural, molecular, and functional changes from the olfactory epithelium to the olfactory bulb and cortex. However, it remains unknown how early experience shapes functional properties of individual olfactory sensory neurons (OSNs), the primary odor detectors in the nose. To address this question, we examined odorant response properties of mouse OSNs in both the closed and open nostril after four weeks of unilateral naris closure with age-matched untreated animals as control. Using patch-clamp technique on genetically-tagged OSNs with defined odorant receptors (ORs), we found that sensory deprivation increased the sensitivity of MOR23 neurons in the closed side while overexposure caused the opposite effect in the open side. We next analyzed the response properties including rise time, decay time, and adaptation induced by repeated stimulation in MOR23 and M71 neurons. Even though these two types of neurons showed distinct properties in dynamic range and response kinetics, sensory deprivation significantly slowed down the decay phase of odorant-induced transduction events in both types. Using western blotting and antibody staining, we confirmed upregulation of several signaling proteins in the closed side as compared with the open side. This study suggests that early experience modulates functional properties of OSNs, probably via modifying the signal transduction cascade. PMID:22703547

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchholz, Bruce A.

The project has two main goals: 1) Identify the types of adducts naphthalene (NA) forms with DNA and 2) determine whether adduct formation correlates with site selective tumor formation in defined subcompartments of the respiratory tract (respiratory and olfactory nasal epithelium and airways of mice, rats and rhesus monkeys). Five tasks are associated with the completion of the goals. Task 1: Contracting and Animal Use Approvals. IACUC and ACURO approvals are complete, The subcontract with UC Davis (UCD) was executed in December 2014. Task 2: Perform In Vitro Study for Goal 1. Rat samples exposed and in freezer while adductmore » standards are being made. Mouse samples need to be exposed in next quarter. Task 3: Perform In Vitro Study for Goal 2. Mouse ex vivo samples completed. Rat and monkey samples need to be completed in the next quarter. Task 4: Sample Preparation and Analysis. Mouse Goal 2 samples completed. Other samples remain to be done. Task 5: Data Interpretation and Reporting. Need rat data to write paper on adduct formation.« less

The neuroregenerative capacity of olfactory stem cells is not limitless: implications for aging.

PubMed

Child, Kevin M; Herrick, Daniel B; Schwob, James E; Holbrook, Eric H; Jang, Woochan

2018-06-22

The olfactory epithelium (OE) of vertebrates is a highly regenerative neuroepithelium, maintained under normal condition by a population of stem and progenitor cells - globose basal cells (GBCs) that also contribute to epithelial reconstitution after injury. However, aging of the OE often leads to neurogenic exhaustion - the disappearance of both GBCs and olfactory sensory neurons (OSNs). Aneuronal tissue may remain as olfactory, with an uninterrupted sheet of apically arrayed microvillar-capped sustentacular cell, or may undergo respiratory metaplasia. We have generated a transgenic mouse model for neurogenic exhaustion using OMP-driven Tet-off regulation of the A subunit of Diphtheria toxin such that the death of mature OSNs is accelerated. As early as 2 months of age the epithelium of transgenic mice, regardless of sex, recapitulates what is seen in the aged OE of humans and rodents. Areas of the epithelium completely lack neurons and GBCs, while the horizontal basal cells, a reserve stem cell population, show no evidence of activation. Surprisingly, other areas that were olfactory undergo respiratory metaplasia. The impact of accelerated neuronal death and reduced innervation on the olfactory bulb (OB) is also examined. Constant neuronal turnover leaves glomeruli shrunken and impacts the dopaminergic interneurons in the periglomerular layer. Moreover, the acceleration of OSN death can be reversed in those areas where some GBCs persist. However, the projection onto the OB recovers incompletely and the reinnervated glomeruli are markedly altered. Thus, the capacity for OE regeneration is tempered when GBCs disappear. SIGNIFICANCE STATEMENT A large percentage of humans lose or suffer a significant decline in olfactory function as they age. Consequently, quality of life suffers, and safety and nutritional status are put at risk. With age, the OE apparently becomes incapable of fully maintaining the neuronal population of the epithelium despite its well-known capacity for recovering from most forms of injury when younger which may contribute to age-related olfactory loss. Efforts to identify the mechanism by which olfactory neurogenesis becomes exhausted with age require a powerful model for accelerating age-related tissue pathology. The current OMP-tTA ; TetO-DTA transgenic mouse model, in which olfactory neurons die when they reach maturity and accelerated death can be aborted to assess the capacity for structural recovery, satisfies that need. Copyright © 2018 the authors.

Ablation of Mouse Adult Neurogenesis Alters Olfactory Bulb Structure and Olfactory Fear Conditioning

PubMed Central

Valley, Matthew T.; Mullen, Tanner R.; Schultz, Lucy C.; Sagdullaev, Botir T.; Firestein, Stuart

2009-01-01

Adult neurogenesis replenishes olfactory bulb (OB) interneurons throughout the life of most mammals, yet during this constant flux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the sub-ventricular zone (SVZ). Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs) born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral deficit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local field potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB. PMID:20582278

Predators Are Attracted to the Olfactory Signals of Prey

PubMed Central

Hughes, Nelika K.; Price, Catherine J.; Banks, Peter B.

2010-01-01

Background Predator attraction to prey social signals can force prey to trade-off the social imperatives to communicate against the profound effect of predation on their future fitness. These tradeoffs underlie theories on the design and evolution of conspecific signalling systems and have received much attention in visual and acoustic signalling modes. Yet while most territorial mammals communicate using olfactory signals and olfactory hunting is widespread in predators, evidence for the attraction of predators to prey olfactory signals under field conditions is lacking. Methodology/Principal Findings To redress this fundamental issue, we examined the attraction of free-roaming predators to discrete patches of scents collected from groups of two and six adult, male house mice, Mus domesticus, which primarily communicate through olfaction. Olfactorily-hunting predators were rapidly attracted to mouse scent signals, visiting mouse scented locations sooner, and in greater number, than control locations. There were no effects of signal concentration on predator attraction to their prey's signals. Conclusions/Significance This implies that communication will be costly if conspecific receivers and eavesdropping predators are simultaneously attracted to a signal. Significantly, our results also suggest that receivers may be at greater risk of predation when communicating than signallers, as receivers must visit risky patches of scent to perform their half of the communication equation, while signallers need not. PMID:20927352

ATP excites mouse vomeronasal sensory neurons through activation of P2X receptors.

PubMed

Vick, J S; Delay, R J

2012-09-18

Purinergic signaling through activation of P2X and P2Y receptors is critically important in the chemical senses. In the mouse main olfactory epithelium (MOE), adenosine 5'-triphosphate (ATP) elicits an increase in intracellular calcium ([Ca(2+)](I)) and reduces the responsiveness of olfactory sensory neurons to odorants through activation of P2X and P2Y receptors. We investigated the role of purinergic signaling in vomeronasal sensory neuron (VSN)s from the mouse vomeronasal organ (VNO), an olfactory organ distinct from the MOE that responds to many conspecific chemical cues. Using a combination of calcium imaging and patch-clamp electrophysiology with isolated VSNs, we demonstrated that ATP elicits an increase in [Ca(2+)](I) and an inward current with similar EC(50)s. Neither adenosine nor the P2Y receptor ligands adenosine 5'-diphosphate, uridine 5'-triphosphate, and uridine-5'-disphosphate could mimic either effect of ATP. Moreover, the increase in [Ca(2+)](I) required the presence of extracellular calcium and the inward current elicited by ATP was partially blocked by the P2X receptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate and 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate. Consistent with the activation of P2X receptors, we detected gene expression of the P2X1 and 3 receptors in the VNO by Reverse transcription polymerase chain reaction (RT-PCR). When co-delivered with dilute urine, a natural stimulus, ATP significantly increased the inward current above that elicited by dilute urine or ATP alone. Mechanical stimulation of the VNO induced the release of ATP, detected by luciferin-luciferase luminometry, and this release of ATP was completely abolished in the presence of the connexin/pannexin hemichannel blocker, carbenoxolone. We conclude that the release of ATP could occur during the activity of the vasomotor pump that facilitates the movement of chemicals into the VNO for detection by VSNs. This mechanism could lead to a global increase in excitability and the chemosensory response in VSNs through activation of P2X receptors. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Survival of mature mouse olfactory sensory neurons labeled genetically perinatally.

PubMed

Holl, Anna-Maria

2018-04-01

The main olfactory epithelium (MOE) of an adult mouse harbors a few million mature olfactory sensory neurons (OSNs), which are traditionally defined as mature by their expression of the olfactory marker protein (OMP). Mature OSNs differentiate in situ from stem cells at the base of the MOE. The consensus view is that mature OSNs have a defined lifespan and then undergo programmed cell death, and that the adult MOE maintains homeostasis by generating new mature OSNs from stem cells. But there is also evidence for mature OSNs that are long-lived. Thus far modern genetic tools have not been applied to quantify survival of a population of OSNs that are mature at a given point in time. Here, a genetic strategy was developed to label irreversibly OMP-expressing OSNs in mice. A gene-targeted OMP-CreERT2 strain was generated in which mature OSNs express an enzymatically inactive version of the Cre recombinase. The fusion protein CreERT2 becomes transiently active when exposed to tamoxifen, and in the presence of a Cre reporter in the genome such as tdRFP, CreERT2-expressing cells become irreversibly labeled. A cohort of mice was generated with the same day of birth by in vitro fertilization and embryo transfer, and injected tamoxifen in their mothers at E18.5 of gestation. I counted RFP immunoreactive cells in the MOE and vomeronasal organ of 36 tamoxifen-exposed OMP-CreERT2 × tdRFP mice from 7 age groups: postnatal day (PD)1.5, PD3.5, PD6.5, 3 weeks, 9 weeks, 6 months, and 12 months. Approximately 7.8% of perinatally labeled cells remain at 12 months, confirming that some mature OSNs are indeed long-lived. The survival curve of the population of perinatally labeled MOE cells can be modeled with a mean half-life of 26 days for the population as a whole, excluding the long-lived cells. Copyright © 2018 The Author. Published by Elsevier Inc. All rights reserved.

The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map.

PubMed

Login, Hande; Håglin, Sofia; Berghard, Anna; Bohm, Staffan

2015-10-07

Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DM(high)-VL(low) expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map. The mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the development of the olfactory sensory map are beginning to be elucidated. Little is known about mechanisms by which sensory stimuli shape the organization of the map after birth. We show that a stimulus-dependent gradient of a retinoic acid-inactivating enzyme Cyp26B1 modifies the composition, localization, and axonal projections of olfactory sensory neuron classes. The mechanism is novel and suggests the interesting possibility that local vitamin A metabolism could also be a mediator of stimulus-dependent modifications of precise spatial connectivity in other parts of the nervous system. Copyright © 2015 the authors 0270-6474/15/3513807-12$15.00/0.

Increases in intracellular calcium via activation of potentially multiple phospholipase C isozymes in mouse olfactory neurons

PubMed Central

Szebenyi, Steven A.; Ogura, Tatsuya; Sathyanesan, Aaron; AlMatrouk, Abdullah K.; Chang, Justin; Lin, Weihong

2014-01-01

Phospholipase C (PLC) and internal Ca2+ stores are involved in a variety of cellular functions. However, our understanding of PLC in mammalian olfactory sensory neurons (OSNs) is generally limited to its controversial role in odor transduction. Here we employed single-cell Ca2+ imaging and molecular approaches to investigate PLC-mediated Ca2+ responses and its isozyme gene transcript expression. We found that the pan-PLC activator m-3M3FBS (25 μM) induces intracellular Ca2+ increases in vast majority of isolated mouse OSNs tested. Both the response amplitude and percent responding cells depend on m-3M3FBS concentrations. In contrast, the inactive analog o-3M3FBS fails to induce Ca2+ responses. The m-3M3FBS-induced Ca2+ increase is blocked by the PLC inhibitor U73122, while its inactive analog U73433 has no effect. Removal of extracellular Ca2+ does not change significantly the m-3M3FBS-induced Ca2+ response amplitude. Additionally, in the absence of external Ca2+, we found that a subset of OSNs respond to an odorant mixture with small Ca2+ increases, which are significantly suppressed by U73122. Furthermore, using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction, we found that multiple PLC isozyme gene transcripts are expressed in olfactory turbinate tissue in various levels. Using RNA in situ hybridization analysis, we further show expression of β4, γ1, γ2 gene transcripts in OSNs. Taken together, our results establish that PLC isozymes are potent enzymes for mobilizing intracellular Ca2+ in mouse OSNs and provide molecular insight for PLC isozymes-mediated complex cell signaling and regulation in the peripheral olfactory epithelium. PMID:25374507

Odor identity coding by distributed ensembles of neurons in the mouse olfactory cortex

PubMed Central

Roland, Benjamin; Deneux, Thomas; Franks, Kevin M; Bathellier, Brice; Fleischmann, Alexander

2017-01-01

Olfactory perception and behaviors critically depend on the ability to identify an odor across a wide range of concentrations. Here, we use calcium imaging to determine how odor identity is encoded in olfactory cortex. We find that, despite considerable trial-to-trial variability, odor identity can accurately be decoded from ensembles of co-active neurons that are distributed across piriform cortex without any apparent spatial organization. However, piriform response patterns change substantially over a 100-fold change in odor concentration, apparently degrading the population representation of odor identity. We show that this problem can be resolved by decoding odor identity from a subpopulation of concentration-invariant piriform neurons. These concentration-invariant neurons are overrepresented in piriform cortex but not in olfactory bulb mitral and tufted cells. We therefore propose that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the olfactory cortex. DOI: http://dx.doi.org/10.7554/eLife.26337.001 PMID:28489003

Electrophysiological mapping of the accessory olfactory bulb of the rabbit (Oryctolagus cuniculus).

PubMed

van Groen, T; Ruardy, L; da Silva, F H

1986-07-01

Field potentials elicited by electrical stimulation of the vomeronasal nerve were measured in the accessory olfactory bulb of the rabbit. Maps were made of the distribution of surface field potentials and of the corresponding depth profiles. The surface maps followed closely the contours of the accessory olfactory bulb: at the frontal border the field potential tended to zero and at the center of the structure the field potential attained a maximum. Depth profiles of the field potentials through the accessory olfactory bulb presented a surface-negative wave and, in depth, a positive wave. The polarity reversal occurred at the deep part of the granule cell layer. The zero equipotential line followed closely the curvature of the granule cell layer. Current source density analysis of the depth profiles revealed a main sink at the external plexiform and granule cell layers. This indicates that the main activity in the accessory olfactory bulb is generated by the synapses between the mitral cells and the granule cells as is found in the main olfactory bulb.

Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor.

PubMed

Pozharskaya, Tatyana; Liang, Jonathan; Lane, Andrew P

2013-09-01

Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed. IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-α expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice. TNFR2 is the minor receptor for TNF-α, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS. © 2013 ARS-AAOA, LLC.

Non-redundant coding of aversive odours in the main olfactory pathway

PubMed Central

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-01-01

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

Non-redundant coding of aversive odours in the main olfactory pathway.

PubMed

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-05-23

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

Cell-specific Expression of CYP2A5 in the Mouse Respiratory Tract: Effects of Olfactory Toxicants

PubMed Central

Piras, Elena; Franzén, Anna; Fernández, Estíbaliz L.; Bergström, Ulrika; Raffalli-Mathieu, Françoise; Lang, Matti; Brittebo, Eva B.

2003-01-01

We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens. PMID:14566026

Toward a Mouse Neuroethology in the Laboratory Environment

PubMed Central

Hellier, Jennifer L.; Ly, Xuan; Koka, Kanthaiah; Tollin, Daniel J.; Restrepo, Diego

2010-01-01

In this report we demonstrate that differences in cage type brought unexpected effects on aggressive behavior and neuroanatomical features of the mouse olfactory bulb. A careful characterization of two cage types, including a comparison of the auditory and temperature environments, coupled with a demonstration that naris occlusion abolishes the neuroanatomical changes, lead us to conclude that a likely important factor mediating the phenotypic changes we find is the olfactory environment of the two cages. We infer that seemingly innocuous changes in cage environment can affect sensory input relevant to mice and elicit profound effects on neural output. Study of the neural mechanisms underlying animal behavior in the laboratory environment should be broadened to include neuroethological approaches to examine how the laboratory environment (beyond animal well-being and enrichment) influences neural systems and behavior. PMID:20613876

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchholz, B. A.

The project has two main goals: 1) Identify the types of adducts naphthalene (NA) forms with DNA and 2) determine whether adduct formation correlates with site selective tumor formation in defined subcompartments of the respiratory tract (respiratory and olfactory nasal epithelium and airways of mice, rats and rhesus monkeys). Five tasks are associated with the completion of the goals. Task 1: Contracting and Animal Use Approvals. IACUC and ACURO approvals are complete. The subcontract with UC Davis (UCD) was executed in December 2014. Task 2: Perform In Vitro Study for Goal 1. Rat and mouse samples exposures completed. Monkey samplesmore » need to be exposed in next quarter. Task 3: Perform In Vitro Study for Goal 2. Mouse and rat ex vivo exposures completed. Monkey samples need to be completed in the next quarter. Task 4: Sample Preparation and Analysis. Mouse and Rat Goal 2 samples completed. Monkey samples remain to be done for Goal 2. Rat samples completed for Goal 1. Mouse and Monkey samples for Goal 1 need to be completed. Task 5: Data Interpretation and Reporting. Poster will be presented at 2016 Society of Toxicology Meeting. Outline for paper on adduct formation complete and similar to poster for SOT meeting.« less

Changes in cell migration and survival in the olfactory bulb of the pcd/pcd mouse.

PubMed

Valero, J; Weruaga, E; Murias, A R; Recio, J S; Curto, G G; Gómez, C; Alonso, J R

2007-06-01

Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals, progenitor cells from the rostral migratory stream (RMS) differentiate into bulbar interneurons that modulate MC activity. In the present work, we studied changes in proliferation, tangential migration, radial migration patterns, and the survival of these newly generated neurons in this neurodegeneration animal model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months before killing in order to label neuroblast incorporation into the OB and to analyze the survival of these cells after differentiation, respectively. Both the organization and cellular composition of the RMS and the differentiation of the newly generated neurons in the OB were studied using specific markers of glial cells, neuroblasts, and mature neurons. No changes were observed in the cell proliferation rate nor in their tangential migration through the RMS, indicating that migrating neuroblasts are only weakly responsive to the alteration in their target region, the OB. However, the absence of MC does elicit differences in the final destination of the newly generated interneurons. Moreover, the loss of MC also produces changes in the survival of the newly generated interneurons, in accordance with the dramatic decrease in the number of synaptic targets available.

Role of a Ubiquitously Expressed Receptor in the Vertebrate Olfactory System

PubMed Central

DeMaria, Shannon; Berke, Allison P.; Van Name, Eric; Heravian, Anisa; Ferreira, Todd

2013-01-01

Odorant cues are recognized by receptors expressed on olfactory sensory neurons, the primary sensory neurons of the olfactory epithelium. Odorant receptors typically obey the “one receptor, one neuron” rule, in which the receptive field of the olfactory neuron is determined by the singular odorant receptor that it expresses. Odor-evoked receptor activity across the population of olfactory neurons is then interpreted by the brain to identify the molecular nature of the odorant stimulus. In the present study, we characterized the properties of a C family G-protein-coupled receptor that, unlike most other odorant receptors, is expressed in a large population of microvillous sensory neurons in the zebrafish olfactory epithelium and the mouse vomeronasal organ. We found that this receptor, OlfCc1 in zebrafish and its murine ortholog Vmn2r1, is a calcium-dependent, low-sensitivity receptor specific for the hydrophobic amino acids isoleucine, leucine, and valine. Loss-of-function experiments in zebrafish embryos demonstrate that OlfCc1 is required for olfactory responses to a diverse mixture of polar, nonpolar, acidic, and basic amino acids. OlfCc1 was also found to promote localization of other OlfC receptor family members to the plasma membrane in heterologous cells. Together, these results suggest that the broadly expressed OlfCc1 is required for amino acid detection by the olfactory system and suggest that it plays a role in the function and/or intracellular trafficking of other olfactory and vomeronasal receptors with which it is coexpressed. PMID:24048853

Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

PubMed Central

Sjölinder, Hong; Jonsson, Ann-Beth

2010-01-01

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

PubMed

Sjölinder, Hong; Jonsson, Ann-Beth

2010-11-18

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

Dynamic expression patterns of ECM molecules in the developing mouse olfactory pathway

PubMed Central

Shay, Elaine L.; Greer, Charles A.; Treloar, Helen B.

2009-01-01

Olfactory sensory neuron (OSN) axons follow stereotypic spatio-temporal paths in the establishment of the olfactory pathway. Extracellular matrix (ECM) molecules are expressed early in the developing pathway and are proposed to have a role in its initial establishment. During later embryonic development, OSNs sort out and target specific glomeruli to form precise, complex topographic projections. We hypothesized that ECM cues may help to establish this complex topography. The aim of this study was to characterize expression of ECM molecules during the period of glomerulogenesis, when synaptic contacts are forming. We examined expression of laminin-1, perlecan, tenascin-C and CSPGs and found a coordinated pattern of expression of these cues in the pathway. These appear to restrict axons to the pathway while promoting axon outgrowth within. Thus, ECM molecules are present in dynamic spatio-temporal positions to affect OSN axons as they navigate to the olfactory bulb and establish synapses. PMID:18570250

Neuronal pattern separation in the olfactory bulb improves odor discrimination learning

PubMed Central

Lagier, Samuel; Begnaud, Frédéric; Rodriguez, Ivan; Carleton, Alan

2015-01-01

Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. Here we show that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) are dynamically reformatted in the network at the timescale of a single breath, giving rise to separated patterns of activity in ensemble of output neurons (mitral/tufted cells; M/T). Strikingly, the extent of pattern separation in M/T assemblies predicts behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimuli distinction, a process that is sculpted by synaptic inhibition. PMID:26301325

Neuronal pattern separation in the olfactory bulb improves odor discrimination learning.

PubMed

Gschwend, Olivier; Abraham, Nixon M; Lagier, Samuel; Begnaud, Frédéric; Rodriguez, Ivan; Carleton, Alan

2015-10-01

Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features, thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns of activity in an ensemble of output neurons, mitral/tufted (M/T) cells. Notably, the extent of pattern separation in M/T assemblies predicted behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimulus distinction, a process that is sculpted by synaptic inhibition.

Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wray, S.; Grant, P.; Gainer, H.

1989-10-01

In situ hybridization histochemistry and immunocytochemistry were used to study the prenatal expression of luteinizing hormone-releasing hormone (LHRH) cells in the mouse. Cells expressing LHRH mRNA and peptide product were first detected on embryonic day 11.5 (E11.5) in the olfactory pit. On E12.5, the majority of LHRH cells were located on tracks extending from the olfactory pit to the base of the telencephalon. From E12.5 to E15.5, LHRH cells were detected in a rostral-to-caudal gradient in forebrain areas. Prior to E12.5, cells expressing LHRH mRNA were not detected in forebrain areas known to contain LHRH cells in postnatal animals. Quantitationmore » of cells expressing LHRH mRNA showed that the number of labeled cells on E12.5 (approximately 800) equaled the number of LHRH cells in postnatal animals, but more than 90% of these cells were located in nasal regions. Between E12.5 and E15.5, the location of LHRH cells shifted. The number of LHRH cells in the forebrain increased, while the number of LHRH cells in nasal regions decreased over this same period. These findings establish that cells first found in the olfactory pit and thereafter in forebrain areas express the LHRH gene and correspond to the position of LHRH immunopositive cells found at these developmental times. To further examine the ontogeny of the LHRH system, immunocytochemistry in combination with (3H)thymidine autoradiography was used to determine when LHRH cells left the mitotic cycle. We show that LHRH neurons exhibit a discrete time of birth, suggesting that they arise as a single neuronal population between E10.0 and E11.0. Postnatal LHRH neurons were birth-dated shortly after differentiation of the olfactory placode and before LHRH mRNA was expressed in cells in the olfactory pit.« less

Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

ERIC Educational Resources Information Center

Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

2004-01-01

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

Luteinizing hormone-releasing hormone (LHRH) in rat olfactory systems.

PubMed

Witkin, J W; Silverman, A J

1983-08-20

The luteinizing hormone-releasing hormone (LHRH) systems of rat olfactory bulbs and nasal areas were studied in neonatal and adult rats. Animals were perfused with Zamboni's fixative and olfactory bulbs with nasal olfactory areas intact were removed, postfixed, and decalcified. LHRH was immunohistochemically demonstrated in unembedded frozen or vibratome sections. Luteinizing hormone-releasing hormone immunoreactive elements were found along the course of the nervus terminalis (NT) and within both the main and accessory olfactory bulbs (MOB and AOB, respectively). Both LHRH neurons and fibers were present in the AOB, but only fibers were detected in the MOB. The fibers of the AOB were not confined to any particular lamina while fibers in the MOB were found mainly in the external plexiform layer. LHRH fibers were found in the mucosa of the olfactory epithelium of the vomeronasal organ in both neonatal and adult rats. The NT probably serves as a source of LHRH fibers for both the AOB and the MOB and for fibers observed in the olfactory epithelium of the vomeronasal organ. Other likely sources of LHRH fibers in the olfactory bulb are discussed.

Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

PubMed Central

Burton, Shawn D.

2015-01-01

Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE STATEMENT Inhibitory granule cells are involved critically in shaping odor-evoked principal neuron activity in the mammalian olfactory bulb, yet little is known about how sensory input activates granule cells. Here, we show that sensory input to the olfactory bulb evokes a barrage of asynchronous synaptic excitation and highly reliable, short-latency synaptic inhibition onto granule cells via a disynaptic feedforward inhibitory circuit involving deep short-axon cells. Feedforward inhibition attenuates local depolarization within granule cell dendritic branches, interacts with asynchronous excitation to suppress granule cell spike-timing precision, and scales in strength with excitation across different levels of sensory input to normalize granule cell firing rates. PMID:26490853

Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse.

PubMed

Cádiz-Moretti, Bernardita; Otero-García, Marcos; Martínez-García, Fernando; Lanuza, Enrique

2016-03-01

The medial amygdaloid nucleus (Me) is a key node in the socio-sexual brain, composed of anterior (MeA), posteroventral (MePV) and posterodorsal (MePD) subdivisions. These subdivisions have been suggested to play a different role in reproductive and defensive behaviours. In the present work we analyse the afferents of the three Me subdivisions using restricted injections of fluorogold in female outbred CD1 mice. The results reveal that the MeA, MePV and MePD share a common pattern of afferents, with some differences in the density of retrograde labelling in several nuclei. Common afferents to Me subdivisions include: the accessory olfactory bulbs, piriform cortex and endopiriform nucleus, chemosensory amygdala (receiving direct inputs from the olfactory bulbs), posterior part of the medial bed nucleus of the stria terminalis (BSTM), CA1 in the ventral hippocampus and posterior intralaminar thalamus. Minor projections originate from the basolateral amygdala and amygdalo-hippocampal area, septum, ventral striatum, several allocortical and periallocortical areas, claustrum, several hypothalamic structures, raphe and parabrachial complex. MeA and MePV share minor inputs from the frontal cortex (medial orbital, prelimbic, infralimbic and dorsal peduncular cortices), but differ in the lack of main olfactory projections to the MePV. By contrast, the MePD receives preferential projections from the rostral accessory olfactory bulb, the posteromedial BSTM and the ventral premammillary nucleus. In summary, the common pattern of afferents to the Me subdivisions and their interconnections suggest that they play cooperative instead of differential roles in the various behaviours (e.g., sociosexual, defensive) in which the Me has been shown to be involved.

Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model.

PubMed

Ahn, Sangzin; Choi, Mooseok; Kim, Hyunju; Yang, Eun-Jeong; Mahmood, Usman; Kang, Seong-Il; Shin, Hyun-Woo; Kim, Dae Woo; Kim, Hye-Sun

2018-04-23

Olfactory loss is known to affect both mood and quality of life. Transient anosmia was induced in mice to study the resulting changes in mood, behavior, and on a molecular level. Transient anosmia was induced by a single intranasal instillation of ZnSO4 in BALB/c mice. Hematoxylin and eosin (HE) staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression-related behavior; while the open field, and elevated plus maze tests were used to evaluate anxiety-related behavior. The mRNA levels of amygdalar corticotropin-releasing hormone (CRH) and hypothalamic glucocorticoid receptor (GR) were quantified using real-time PCR to confirm relevant molecular change. Olfactory loss was confirmed 1-2.5 weeks after induction, and this loss was subsequently reversed over time. The results of the behavioral tests indicated increased depression-like and reduced anxiety-like behavior at week 1. Accordingly, PCR data identified decreased amygdalar CRH expression at week 1. These results suggest that transient anosmia induces both depressive and anxiolytic behavior as a result of decreased amygdalar CRH in a mouse model of anosmia.

In vivo bioelectronic nose using transgenic mice for specific odor detection.

PubMed

Gao, Keqiang; Li, Songmin; Zhuang, Liujing; Qin, Zhen; Zhang, Bin; Huang, Liquan; Wang, Ping

2018-04-15

The olfactory system is a natural biosensor since its peripheral olfactory sensory neurons (OSNs) respond to the external stimuli and transmit the signals to the olfactory bulb (OB) where they are integrated and processed. The axonal connections from the OSNs expressing about 1000 different types of odorant receptors are precisely organized and sorted out onto 1800 glomeruli in the OB, from which the olfactory information is delivered to and perceived by the central nervous system. This process is carried out with particularly high sensitivity, specificity and rapidity, which can be used for explosive detection. Biomimetic olfactory biosensors use various biological components from the olfactory system as sensing elements, possessing great commercial prospects. In this study, we utilized the genetically labeled murine M72 olfactory sensory neurons with the green fluorescent protein (GFP) as sensing components and obtained long-term in vivo electrophysiological recordings from the M72 OSNs by implanting the microelectrode arrays (MEAs) into the behaving mouse's OB. The electrophysiological responses showed high reliability, reproducibility and specificity for odor detection, and particularly, the high sensitivity for the detection of odorants that contain benzene rings. Furthermore, our results indicated that it can detect trinitrotoluene (TNT) in liquid at a concentration as low as 10 -5 M and can distinguish TNT from other chemicals with a similar structure. Thus our study demonstrated that the in vivo biomimetic olfactory system could provide novel approaches to enhancing the specificity and increasing working lifespan of olfactory biosensors capable of detecting explosives. Copyright © 2017 Elsevier B.V. All rights reserved.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

PubMed

Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

2012-01-01

Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h) or day (10:00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

PubMed Central

Chery, Romain; L'Heureux, Barbara; Bendahmane, Mounir; Renaud, Rémi; Martin, Claire; Pain, Frédéric; Gurden, Hirac

2011-01-01

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4. The olfactory system is of central importance for the survival of the vast majority of living species because it allows efficient detection and identification of chemical substances in the environment (food, predators). The OB is the first relay of olfactory information processing in the brain. It receives afferent projections from the olfactory primary sensory neurons that detect volatile odorant molecules. Each sensory neuron expresses only one type of odorant receptor and neurons carrying the same type of receptor send their nerve processes to the same well-defined microregions of ˜100μm3 constituted of discrete neuropil, the olfactory glomerulus (Fig. 1). In the last decade, IOS imaging has fostered the functional exploration of the OB5, 6, 7 which has become one of the most studied sensory structures. The mapping of OB activity with FAS imaging has not been performed yet. Here, we show the successive steps of an efficient protocol for IOS and FAS imaging to map odor-evoked activities in the mouse OB. PMID:22064685

[The role of metabolic activation of promutagens in the genome destabilization under pheromonal stress in the house mouse (Mus musculus)].

PubMed

Zhuk, A S; Stepchenkova, E I; Dukel'skaia, A V; Daev, E V; Inge-Vechtomov, S G

2011-10-01

The hypothesis on a relationship between the high frequency of mitotic disturbances in bone marrow cells and the change in the activity of the S9 liver fraction containing promutagen-activating enzymes under olfactory stress in the house mouse Mus musculus has been tested. For this purpose, the effect of the pheromone 2,5-dimethylpyrazine on the frequency of mitotic disturbances in mouse bone marrow cells has been measured by the anaphase-telophase assay. The Ames test using Salmonella typhimurium has been employed to compare the capacities of the S9 liver fractions from stressed and intact mice for activating the promutagen 2-aminofluorene. It has been demonstrated that the increased frequency of mitotic disturbances in bone marrow cells induced by the pheromonal stressor in male house mice is accompanied by an increased promutagen-activating capacity of the S9 liver fraction. The model system used in the study allowed the genetic consequences of the exposure to the olfactory stressor to be estimated and the possible mechanisms of genome destabilization to be assumed.

Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.

PubMed

Ahn, Sangzin; Shin, Hyun-Woo; Mahmood, Usman; Khalmuratova, Roza; Jeon, Sea-Yuong; Jin, Hong Ryul; Choi, Jung-Seok; Kim, Hye-Sun; Kim, Dae Woo

2016-03-01

Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.

Changes in the serotonergic system in the main olfactory bulb of rats unilaterally deprived from birth to adulthood.

PubMed

Gómez, C; Briñón, J G; Orio, L; Colado, M I; Lawrence, A J; Zhou, F C; Vidal, M; Barbado, M V; Alonso, J R

2007-02-01

The serotonergic system plays a key role in the modulation of olfactory processing. The present study examined the plastic response of this centrifugal system after unilateral naris occlusion, analysing both serotonergic afferents and receptors in the main olfactory bulb. After 60 days of sensory deprivation, the serotonergic system exhibited adaptive changes. Olfactory deprivation caused a general increase in the number of fibres immunopositive for serotonin but not of those immunopositive for the serotonin transporter. HPLC data revealed an increase in serotonin levels but not in those of its major metabolite, 5-hydroxyindole acetic acid, resulting in a decrease in the 5-hydroxyindole acetic acid/serotonin ratio. These changes were observed not only in the deprived but also in the contralateral olfactory bulb. Double serotonin-tyrosine hydroxylase immunolabelling revealed that the glomerular regions of the deprived olfactory bulb with a high serotonergic fibre density showed a strong reduction in tyrosine hydroxylase. Finally, the serotonin(2A) receptor distribution density and the number of juxtaglomerular cells immunopositive for serotonin(2A) receptor remained unaltered after olfactory deprivation. Environmental stimulation modulated the serotonergic afferents to the olfactory bulb. Our results indicate the presence of a bilateral accumulation of serotonin in the serotonergic axon network, with no changes in serotonin(2A) receptor density after unilateral olfactory deprivation.

Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb.

PubMed

Gómez, C; Briñón, J G; Barbado, M V; Weruaga, E; Valero, J; Alonso, J R

2005-06-01

The centrifugal systems innervating the olfactory bulb are important elements in the functional regulation of the olfactory pathway. In this study, the selective innervation of specific glomeruli by serotonergic, noradrenergic and cholinergic centrifugal axons was analyzed. Thus, the morphology, distribution and density of positive axons were studied in the glomerular layer of the main olfactory bulb of the rat, using serotonin-, serotonin transporter- and dopamine-beta-hydroxylase-immunohistochemistry and acetylcholinesterase histochemistry in serial sections. Serotonin-, serotonin transporter-immunostaining and acetylcholinesterase-staining revealed a higher heterogeneity in the glomerular layer of the main olfactory bulb than previously reported. In this sense, four types of glomeruli could be identified according to their serotonergic innervation. The main distinctive feature of these four types of glomeruli was their serotonergic fibre density, although they also differed in their size, morphology and relative position throughout the rostro-caudal main olfactory bulb. In this sense, some specific regions of the glomerular layer were occupied by glomeruli with a particular morphology and a characteristic serotonergic innervation pattern that was consistent from animal to animal. Regarding the cholinergic system, we offer a new subclassification of glomeruli based on the distribution of cholinergic fibres in the glomerular structure. Finally, the serotonergic and cholinergic innervation patterns were compared in the glomerular layer. Sexual differences concerning the density of serotonergic fibres were observed in the atypical glomeruli (characterized by their strong cholinergic innervation). The present report provides new data on the heterogeneity of the centrifugal innervation of the glomerular layer that constitutes the morphological substrate supporting the existence of differential modulatory levels among the entire glomerular population.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Exercise Is Associated with Lower Long-Term Risk of Olfactory Impairment in Older Adults

PubMed Central

Schubert, Carla R.; Cruickshanks, Karen J.; Nondahl, David M.; Klein, Barbara EK; Klein, Ronald; Fischer, Mary E.

2013-01-01

Importance The prevalence of olfactory impairment is high in older adults and this decline in olfactory ability may pose health and safety risks, affect nutrition and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objectives To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n=1611) were ages 53-97 years at baseline and were followed for up to ten years (1998-2010). Interventions None Main Outcome and Measures Olfaction was measured with the San Diego Odor Identification Test at three examinations (1998-2000, 2003-2005, 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment five (2003-2005) or ten (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% confidence interval =25.3, 29.9) and rates varied by age and sex; those who were older (Hazard Ratio =1.88, 95% Confidence Interval=1.74, 2.03, for every 5 years) or male (Hazard Ratio=1.27, 95% Confidence Interval=1.00, 1.61) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age and sex adjusted Hazard Ratio= 0.76, 95% CI= 0.60, 0.97). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment (p for trend = 0.02). Conclusion and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age. PMID:24135745

Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress

PubMed Central

Belnoue, Laure; Malvaut, Sarah; Ladevèze, Elodie; Abrous, Djoher Nora; Koehl, Muriel

2016-01-01

Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers’ ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers. PMID:27886228

[Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

PubMed

Sánchez-Criado, J E

1979-06-01

The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

PubMed Central

Puche, Adam C.; Munger, Steven D.

2016-01-01

The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model

PubMed Central

Marjonen, Heidi; Sierra, Alejandra; Nyman, Anna; Rogojin, Vladimir; Gröhn, Olli; Linden, Anni-Maija; Hautaniemi, Sampsa; Kaminen-Ahola, Nina

2015-01-01

The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P) 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60): we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in different tissue types later in life. PMID:25970770

Inhalation Frequency Controls Reformatting of Mitral/Tufted Cell Odor Representations in the Olfactory Bulb.

PubMed

Díaz-Quesada, Marta; Youngstrom, Isaac A; Tsuno, Yusuke; Hansen, Kyle R; Economo, Michael N; Wachowiak, Matt

2018-02-28

In mammals, olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and tufted (MT) cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT cell odor responses, we obtained whole-cell recordings from MT cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across cells. We characterized frequency effects on MT cell responses during inhalation of air and odorants using inhalation pulses and also "playback" of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well predicted across frequency from linear convolution of 1 Hz responses; and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT cells, with some cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling. SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on inhalation, which increases in frequency during active sampling of olfactory stimuli. We asked how inhalation frequency can shape the neural coding of odor information by recording from projection neurons of the olfactory bulb while artificially varying odor sampling frequency in the anesthetized mouse. We found that sampling an odor at higher frequencies led to diverse changes in net responsiveness, as measured by action potential output, that were not predicted from low-frequency responses. These changes led to a reorganization of the pattern of neural activity evoked by a given odorant that occurred preferentially during sustained, high-frequency inhalation. These results point to a novel mechanism for modulating early sensory representations solely as a function of sampling behavior. Copyright © 2018 the authors 0270-6474/18/382189-18$15.00/0.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

PubMed Central

Saven, Jeffery G.; Matsunami, Hiroaki; Eckenhoff, Roderic G.

2015-01-01

Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug. PMID:25829447

Stereochemical study of mouse muscone receptor MOR215-1 and vibrational theory based on statistical physics formalism.

PubMed

Ben Khemis, Ismahene; Mechi, Nesrine; Ben Lamine, Abdelmottaleb

2018-02-10

In the biosensor system, olfactory receptor sites could be activated by odorant molecules and then the biological interactions are converted into electrical signals by a signal transduction cascade that leads the toopening of ion channels, generating a current that leads into the cilia and depolarizes the membrane. The aim of this paper is to present a new investigation that allows determining the olfactory band using a monolayer adsorption with identical sites modeling which may also describe the static and the dynamic sensitivities through the expression of the olfactory response. Moreover, knowing the size of receptor site in olfactory sensory neurons provides valuable information about the relationship between molecular structure and biological activity. The determination of microreceptors and mesoreceptors is mostly carried out via physical adsorption and the radius is calculated using the Kelvin equation. The mean values of radius obtained from the maximum of the receptor size distributions peaks are 4 nm for ℓ-muscone and 6 nm for d-muscone. Copyright © 2018. Published by Elsevier Ltd.

Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates

PubMed Central

Wiebe, Victor; Przeworski, Molly; Lancet, Doron; Pääbo, Svante

2004-01-01

Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates. PMID:14737185

Organization of the main olfactory bulbs of some mammals: musk shrews, moles, hedgehogs, tree shrews, bats, mice, and rats.

PubMed

Kosaka, Katsuko; Kosaka, Toshio

2004-04-19

We immunohistochemically examined the organization of the main olfactory bulbs (MOBs) in seven mammalian species, including moles, hedgehogs, tree shrews, bats, and mice as well as laboratory musk shrews and rats. We focused our investigation on two points: 1) whether nidi, particular spheroidal synaptic regions subjacent to glomeruli, which we previously reported for the laboratory musk shrew MOBs, are also present in other animals and 2) whether the compartmental organization of glomeruli and two types of periglomerular cells we proposed for the rat MOBs are general in other animals. The general laminar pattern was similar among these seven species, but discrete nidi and the nidal layer were recognized only in two insectivores, namely, the mole and laboratory musk shrew. Olfactory marker protein-immunoreactive (OMP-IR) axons extended beyond the limits of the glomerular layer (GL) into the superficial region of the external plexiform layer (EPL) or the nidal layer in the laboratory musk shrew, mole, hedgehog, and tree shrew but not in bat, mouse, and rat. We observed, in nidi and the nidal layer in the mole and laboratory musk shrew MOBs, only a few OMP-IR axons. In the hedgehog, another insectivore, OMP-IR processes extending from the glomeruli were scattered and intermingled with calbindin D28k-IR cells at the border between the GL and the EPL. In the superficial region of the EPL of the tree shrew MOBs, there were a small number of tiny glomerulus-like spheroidal structures where OMP-IR axons protruding from glomeruli were intermingled with dendritic branches of surrounding calbindin D28k-IR cells. Furthermore, we recognized the compartmental organization of glomeruli and two types of periglomerular cells in the MOBs of all of the mammals we examined. These structural features are therefore considered to be common and important organizational principles of the MOBs. Copyright 2004 Wiley-Liss, Inc.

Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice

PubMed Central

Dong, Frederick N.

2017-01-01

Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia- and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type α-helical repeats, which may mediate protein–protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior. SIGNIFICANCE STATEMENT Sensory receptor cells are generally thought to evolve to respond to sensory cues as fast as they can. This idea is consistent with mutational analyses in various sensory systems, where mutations of sensory receptor cells often resulted in reduced response size and slowed response kinetics. Contrary to this idea, we have found that there is a kinetic “damper” present in the olfactory transduction cascade of the mouse that slows down the response kinetics and, by doing so, it reduces the peripheral temporal resolution in coding odor stimuli and allows for robust olfactory behavior. This study should trigger a rethinking of the significance of the intrinsic speed of sensory transduction and the pattern of the peripheral coding of sensory stimuli. PMID:28495971

Olfactory discrimination varies in mice with different levels of α7-nicotinic acetylcholine receptor expression.

PubMed

Hellier, Jennifer L; Arevalo, Nicole L; Blatner, Megan J; Dang, An K; Clevenger, Amy C; Adams, Catherine E; Restrepo, Diego

2010-10-28

Previous studies have shown that schizophrenics have decreased expression of α7-nicotinic acetylcholine (α7) receptors in the hippocampus and other brain regions, paranoid delusions, disorganized speech, deficits in auditory gating (i.e., inability to inhibit neuronal responses to repetitive auditory stimuli), and difficulties in odor discrimination and detection. Here we use mice with decreased α7 expression that also show a deficit in auditory gating to determine if these mice have similar deficits in olfaction. In the adult mouse olfactory bulb (OB), α7 expression localizes in the glomerular layer; however, the functional role of α7 is unknown. We show that inbred mouse strains (i.e., C3H and C57) with varying α7 expressions (e.g., α7 wild-type [α7+/+], α7 heterozygous knock-out [α7+/-] and α7 homozygous knock-out mice [α7-/-]) significantly differ in odor discrimination and detection of chemically-related odorant pairs. Using [(125)I] α-bungarotoxin (α-BGT) autoradiography, α7 expression was measured in the OB. As previously demonstrated, α-BGT binding was localized to the glomerular layer. Significantly more expression of α7 was observed in C57 α7+/+ mice compared to C3H α7+/+ mice. Furthermore, C57 α7+/+ mice were able to detect a significantly lower concentration of an odor in a mixture compared to C3H α7+/+ mice. Both C57 and C3H α7+/+ mice discriminated between chemically-related odorants sooner than α7+/- or α7-/- mice. These data suggest that α7-nicotinic-receptors contribute strongly to olfactory discrimination and detection in mice and may be one of the mechanisms producing olfactory dysfunction in schizophrenics. Copyright © 2010 Elsevier B.V. All rights reserved.

ATP Mediates Neuroprotective and Neuroproliferative Effects in Mouse Olfactory Epithelium following Exposure to Satratoxin G In Vitro and In Vivo

PubMed Central

Jia, Cuihong; Sangsiri, Sutheera; Belock, Bethany; Iqbal, Tania R.; Pestka, James J.; Hegg, Colleen C.

2011-01-01

Intranasal aspiration of satratoxin G (SG), a mycotoxin produced by the black mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) in mouse olfactory epithelium (OE) through unknown mechanisms. Here, we show a dose-dependent induction of apoptosis 24 h post-SG exposure in vitro as measured by increased activated caspases in the OP6 olfactory placodal cell line and increased propidium iodide staining in primary OE cell cultures. Intranasal aspiration of SG increased TUNEL (Terminal dUTP Nick End Labeling) staining in the neuronal layer of the OE and significantly increased the latency to find a buried food pellet, confirming that SG selectively induces neuronal apoptosis and demonstrating that SG impairs the sense of smell. Next, we investigated whether ATP can prevent SG-induced OE toxicity. ATP did not decrease apoptosis under physiological conditions but significantly reduced SG-induced OSN apoptosis in vivo and in vitro. Furthermore, purinergic receptor inhibition significantly increased apoptosis in OE primary cell culture and in vivo. These data indicate that ATP is neuroprotective against SG-induced OE toxicity. The number of cells that incorporated 5′-bromodeoxyuridine, a measure of proliferation, was significantly increased 3 and 6 days post-SG aspiration. Treatment with purinergic receptor antagonists significantly reduced SG-induced cell proliferation, whereas post-treatment with ATP significantly potentiated SG-induced cell proliferation. These data indicate that ATP is released and promotes cell proliferation via activation of purinergic receptors in SG-induced OE injury. Thus, the purinergic system is a therapeutic target to alleviate or restore the loss of OSNs. PMID:21865290

Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

PubMed Central

Etgen, Anne M.; Dobrenis, Kostantin; Pollard, Jeffrey W.

2011-01-01

The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1op) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure. PMID:22046273

Perforated Patch-clamp Recording of Mouse Olfactory Sensory Neurons in Intact Neuroepithelium: Functional Analysis of Neurons Expressing an Identified Odorant Receptor

PubMed Central

Jarriault, David; Grosmaitre, Xavier

2015-01-01

Analyzing the physiological responses of olfactory sensory neurons (OSN) when stimulated with specific ligands is critical to understand the basis of olfactory-driven behaviors and their modulation. These coding properties depend heavily on the initial interaction between odor molecules and the olfactory receptor (OR) expressed in the OSNs. The identity, specificity and ligand spectrum of the expressed OR are critical. The probability to find the ligand of the OR expressed in an OSN chosen randomly within the epithelium is very low. To address this challenge, this protocol uses genetically tagged mice expressing the fluorescent protein GFP under the control of the promoter of defined ORs. OSNs are located in a tight and organized epithelium lining the nasal cavity, with neighboring cells influencing their maturation and function. Here we describe a method to isolate an intact olfactory epithelium and record through patch-clamp recordings the properties of OSNs expressing defined odorant receptors. The protocol allows one to characterize OSN membrane properties while keeping the influence of the neighboring tissue. Analysis of patch-clamp results yields a precise quantification of ligand/OR interactions, transduction pathways and pharmacology, OSNs' coding properties and their modulation at the membrane level.  PMID:26275097

Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

PubMed

Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Wang, Xiaomei; Wang, Cong

2017-01-01

Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus .

Functional transformations of odor inputs in the mouse olfactory bulb.

PubMed

Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

2014-01-01

Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams.

A role for TENM1 mutations in congenital general anosmia.

PubMed

Alkelai, A; Olender, T; Haffner-Krausz, R; Tsoory, M M; Boyko, V; Tatarskyy, P; Gross-Isseroff, R; Milgrom, R; Shushan, S; Blau, I; Cohn, E; Beeri, R; Levy-Lahad, E; Pras, E; Lancet, D

2016-09-01

Congenital general anosmia (CGA) is a neurological disorder entailing a complete innate inability to sense odors. While the mechanisms underlying vertebrate olfaction have been studied in detail, there are still gaps in our understanding of the molecular genetic basis of innate olfactory disorders. Applying whole-exome sequencing to a family multiply affected with CGA, we identified three members with a rare X-linked missense mutation in the TENM1 (teneurin 1) gene (ENST00000422452:c.C4829T). In Drosophila melanogaster, TENM1 functions in synaptic-partner-matching between axons of olfactory sensory neurons and target projection neurons and is involved in synapse organization in the olfactory system. We used CRISPR-Cas9 system to generate a Tenm1 disrupted mouse model. Tenm1(-/-) and point-mutated Tenm1(A) (/A) adult mice were shown to have an altered ability to locate a buried food pellet. Tenm1(A) (/A) mice also displayed an altered ability to sense aversive odors. Results of our study, that describes a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction. However, additional studies should be done in larger CGA cohorts, to provide statistical evidence that loss-of-function mutations in TENM1 can solely cause the disease in our and other CGA cases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening

PubMed Central

Harini, K.; Sowdhamini, Ramanathan

2015-01-01

Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors. PMID:26221959

Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb.

PubMed

Uchida, Sae; Kagitani, Fusako

2017-05-12

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of L-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

Olfactory projection neuron pathways in two species of marine Isopoda (Peracarida, Malacostraca, Crustacea).

PubMed

Stemme, Torben; Eickhoff, René; Bicker, Gerd

2014-08-01

The neuroanatomy of the olfactory pathway has been intensely studied in many representatives of Malacostraca. Nevertheless, the knowledge about bilateral olfactory integration pathways is mainly based on Decapoda. Here, we investigated the olfactory projection neuron pathway of two marine isopod species, Saduria entomon and Idotea emarginata, by lipophilic dye injections into the olfactory neuropil. We show that both arms of the olfactory globular tract form a chiasm in the center of the brain, as known from several other crustaceans. Furthermore, the olfactory projection neurons innervate both the medulla terminalis and the hemiellipsoid body of the ipsi- and the contralateral hemisphere. Both protocerebral neuropils are innervated to a comparable extent. This is reminiscent of the situation in the basal decapod taxon Dendrobranchiata. Thus, we propose that an innervation by the olfactory globular tract of both the medulla terminalis and the hemiellipsoid body is characteristic of the decapod ground pattern, but also of the ground pattern of Caridoida. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preprocessing of emotional visual information in the human piriform cortex.

PubMed

Schulze, Patrick; Bestgen, Anne-Kathrin; Lech, Robert K; Kuchinke, Lars; Suchan, Boris

2017-08-23

This study examines the processing of visual information by the olfactory system in humans. Recent data point to the processing of visual stimuli by the piriform cortex, a region mainly known as part of the primary olfactory cortex. Moreover, the piriform cortex generates predictive templates of olfactory stimuli to facilitate olfactory processing. This study fills the gap relating to the question whether this region is also capable of preprocessing emotional visual information. To gain insight into the preprocessing and transfer of emotional visual information into olfactory processing, we recorded hemodynamic responses during affective priming using functional magnetic resonance imaging (fMRI). Odors of different valence (pleasant, neutral and unpleasant) were primed by images of emotional facial expressions (happy, neutral and disgust). Our findings are the first to demonstrate that the piriform cortex preprocesses emotional visual information prior to any olfactory stimulation and that the emotional connotation of this preprocessing is subsequently transferred and integrated into an extended olfactory network for olfactory processing.

Development of the olfactory pathways in platypus and echidna.

PubMed

Ashwell, Ken W S

2012-01-01

The two groups of living monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum für Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching. Copyright © 2011 S. Karger AG, Basel.

Cladistic Analysis of Olfactory and Vomeronasal Systems

PubMed Central

Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

2010-01-01

Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses. PMID:21290004

Cladistic analysis of olfactory and vomeronasal systems.

PubMed

Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

2011-01-01

Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies' view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical "cortex." We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

Cell density and intracellular translocation of glucocorticoid receptor-immunoreactive neurons in the kokanee salmon (Oncorhynchus nerka kennerlyi) brain, with an emphasis on the olfactory system.

PubMed

Carruth, L L; Jones, R E; Norris, D O

2000-01-01

This study tested the hypothesis that neurons in olfactory regions of the kokanee salmon brain contain glucocorticoid receptors. Distribution and neuronal number of glucocorticoid receptor-like immunoreactive (GRir) neurons were identified in the kokanee salmon brain using immunohistochemistry with an antibody to GR (polyclonal rabbit anti-human, dilution 1:1500; and monoclonal mouse, dilution 5 micrograms/ml). Distribution of GRir neurons similar to the mammalian pattern was observed in the brains of sexually immature (n = 8; 4 female and 4 male) as well as spawning (n = 8; 4 female and 4 male) salmon. Olfactory-related areas containing GRir positive neuronal bodies included the internal cell layer of the olfactory bulb, ventral-lateral and lateral parts of the dorsal telencephalon (homologue of the mammalian hippocampus), ventral area of the telencephalon (homologue of the mammalian amygdala), glomerulosus complex of the thalamus, the preoptic area, and inferior lobe of the hypothalamus. The pattern of GRir neuronal distribution in sexually immature and spawning fish was similar. However, spawning fish brains, compared to sexually immature brains, exhibited a significantly greater GRir neuronal number in several olfactory regions in paired immunohistochemical runs. There also were differences in intraneuronal location of GRir in olfactory regions, with staining being predominantly cytoplasmic in sexually immature fish but nuclear in spawning fish. These results are consistent with a role for cortisol in olfactory-mediated homing in kokanee salmon. Although GRir were identified in many nonolfactory regions, the focus of this study is on GRir present in brain regions involved in olfaction. Copyright 2000 Academic Press.

Stimulation of Electro-Olfactogram Responses in the Main Olfactory Epithelia by Airflow Depend on the Type 3 Adenylyl Cyclase

PubMed Central

Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R.

2012-01-01

Cilia of olfactory sensory neurons (OSN) are the primary sensory organelles for olfaction. The detection of odorants by the main olfactory epithelium (MOE) depends on coupling of odorant receptors to the type 3 adenylyl cyclase (AC3) in olfactory cilia. We monitored the effect of airflow on electro-olfactogram (EOG) responses and found that the MOE of mice can sense mechanical forces generated by airflow. The airflow-sensitive EOG response in the MOE was attenuated when cAMP was increased by odorants or by forskolin suggesting a common mechanism for airflow and odorant detection. In addition, the sensitivity to airflow was significantly impaired in the MOE from AC3−/− mice. We conclude that AC3 in the MOE is required for detecting the mechanical force of airflow, which in turn may regulate odorant perception during sniffing. PMID:23136416

Odorant Sensory Input Modulates DNA Secondary Structure Formation and Heterogeneous Ribonucleoprotein Recruitment on the Tyrosine Hydroxylase and Glutamic Acid Decarboxylase 1 Promoters in the Olfactory Bulb.

PubMed

Wang, Meng; Cai, Elizabeth; Fujiwara, Nana; Fones, Lilah; Brown, Elizabeth; Yanagawa, Yuchio; Cave, John W

2017-05-03

Adaptation of neural circuits to changes in sensory input can modify several cellular processes within neurons, including neurotransmitter biosynthesis levels. For a subset of olfactory bulb interneurons, activity-dependent changes in GABA are reflected by corresponding changes in Glutamate decarboxylase 1 ( Gad1 ) expression levels. Mechanisms regulating Gad1 promoter activity are poorly understood, but here we show that a conserved G:C-rich region in the mouse Gad1 proximal promoter region both recruits heterogeneous nuclear ribonucleoproteins (hnRNPs) that facilitate transcription and forms single-stranded DNA secondary structures associated with transcriptional repression. This promoter architecture and function is shared with Tyrosine hydroxylase ( Th ), which is also modulated by odorant-dependent activity in the olfactory bulb. This study shows that the balance between DNA secondary structure formation and hnRNP binding on the mouse Th and Gad1 promoters in the olfactory bulb is responsive to changes in odorant-dependent sensory input. These findings reveal that Th and Gad1 share a novel transcription regulatory mechanism that facilitates sensory input-dependent regulation of dopamine and GABA expression. SIGNIFICANCE STATEMENT Adaptation of neural circuits to changes in sensory input can modify several cellular processes within neurons, including neurotransmitter biosynthesis levels. This study shows that transcription of genes encoding rate-limiting enzymes for GABA and dopamine biosynthesis ( Gad1 and Th , respectively) in the mammalian olfactory bulb is regulated by G:C-rich regions that both recruit heterogeneous nuclear ribonucleoproteins (hnRNPs) to facilitate transcription and form single-stranded DNA secondary structures associated with repression. hnRNP binding and formation of DNA secondary structure on the Th and Gad1 promoters are mutually exclusive, and odorant sensory input levels regulate the balance between these regulatory features. These findings reveal that Th and Gad1 share a transcription regulatory mechanism that facilitates odorant-dependent regulation of dopamine and GABA expression levels. Copyright © 2017 the authors 0270-6474/17/374778-12$15.00/0.

Species and sex differences in susceptibility to olfactory lesions among the mouse, rat and monkey following an intravenous injection of vincristine sulphate.

PubMed

Kai, Kiyonori; Sahto, Hiroshi; Yoshida, Mitsuyoshi; Suzuki, Takami; Shikanai, Yukari; Kajimura, Tetsuyo; Furuhama, Kazuhisa

2006-01-01

Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.6-fold LD10 and LD10 were used for mice and rats, and a maximum tolerated dose (MTD) was chosen only for monkeys. The order of strength of VCR action on peripheral neuropathic signs, body weight gain, and hematological parameters was mice > rats > monkeys, without clear sex differences. Histopathologically, on day 2, single cell death in the olfactory epithelium and vomeronasal organ was observed only in male mice at LD10, and in female mice at 0.6-fold LD10 or more. On day 5, the olfactory epithelium in these mice showed regenerative proliferation suggesting a sign of recovery. On day 10, axonopathy and demyelination in the sciatic and trigeminal nerves were noted in mice of both sexes at 0.6-fold LD10 or more. In rats and monkeys of either sex, however, no morphological changes were observed at any dose level. In conclusion, mice, particularly females, were shown to be more susceptible to VCR-induced apoptosis in the olfactory epithelium than rats and monkeys.

Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: A patch clamp analysis in gene-targeted mice

PubMed Central

Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M.; Ma, Minghong

2006-01-01

A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli. PMID:16446455

Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice.

PubMed

Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M; Ma, Minghong

2006-02-07

A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli.

Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity.

PubMed

Ferguson, Christopher H; Zhao, Haiqing

2017-01-04

In vertebrate olfactory sensory neurons (OSNs), Ca 2+ plays key roles in both mediating and regulating the olfactory response. Ca 2+ enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca 2+ -activated chloride channel to amplify the response. Ca 2+ also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca 2+ /calmodulin (CaM), to reduce the response. Ca 2+ is removed from the cilia primarily by the K + -dependent Na + /Ca 2+ exchanger 4 (NCKX4), and the removal of Ca 2+ leads to closure of the chloride channel and response termination. In this study, we investigate how two mechanisms conventionally considered negative regulatory mechanisms of olfactory transduction, Ca 2+ removal by NCKX4, and desensitization of the CNG channel by Ca 2+ /CaM, interact to regulate the olfactory response. We performed electro-olfactogram (EOG) recordings on the double-mutant mice, NCKX4 -/- ;CNGB1 ΔCaM , which are simultaneously lacking NCKX4 (NCKX4 -/- ) and Ca 2+ /CaM-mediated CNG channel desensitization (CNGB1 ΔCaM ). Despite exhibiting alterations in various response attributes, including termination kinetics and adaption properties, OSNs in either NCKX4 -/- mice or CNGB1 ΔCaM mice show normal resting sensitivity, as determined by their unchanged EOG response amplitude. We found that OSNs in NCKX4 -/- ;CNGB1 ΔCaM mice displayed markedly reduced EOG amplitude accompanied by alterations in other response attributes. This study suggests that what are conventionally considered negative regulatory mechanisms of olfactory transduction also play a role in setting the resting sensitivity in OSNs. Sensory receptor cells maintain high sensitivity at rest. Although the mechanisms responsible for setting the resting sensitivity of sensory receptor cells are not well understood, it has generally been assumed that the sensitivity is set primarily by how effectively the components in the activation cascade of sensory transduction can be stimulated. Our findings in mouse olfactory sensory neurons suggest that mechanisms that are primarily responsible for terminating the olfactory response are also critical for proper resting sensitivity. Copyright © 2017 the authors 0270-6474/17/370110-10$15.00/0.

Uptake and transport of manganese in primary and secondary olfactory neurones in pike.

PubMed

Tjälve, H; Mejàre, C; Borg-Neczak, K

1995-07-01

gamma-spectrometry and autoradiography were used to examine the axoplasmic flow of manganese in the olfactory nerves and to study the uptake of the metal in the brain after application of 54Mn2+ in the olfactory chambers of pikes. The results show that the 54Mn2+ is taken up in the olfactory receptor cells and is transported at a constant rate along the primary olfactory neurones into the brain. The maximal velocity for the transported 54Mn2+ was 2.90 +/- 0.21 mm/hr (mean +/- S.E.) at 10 degrees, which was the temperature used in the experiments. The 54Mn2+ accumulated in the entire olfactory bulbs, although most marked in central and caudal parts. The metal was also seen to migrate into large areas of the telencephalon, apparently mainly via the secondary olfactory axons present in the medial olfactory tract. A transfer along fibres of the medial olfactory tract probably also explains the labelling which was seen in the diencephalon down to the hypothalamus. The results also showed that there is a pathway connecting the two olfactory bulbs of the pike and that this can carry the metal. Our data further showed a marked accumulation of 54Mn2+ in the meningeal epithelium and in the contents of the meningeal sacs surrounding the olfactory bulbs. It appears from our study that manganese has the ability to pass the synaptic junctions between the primary and the secondary olfactory neurones in the olfactory bulbs and to migrate along secondary olfactory pathways into the telencephalon and the diencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

PubMed Central

2007-01-01

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use. PMID:17903277

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

PubMed

Carlson, Kaitlin S; Whitney, Meredith S; Gadziola, Marie A; Deneris, Evan S; Wesson, Daniel W

2016-01-01

The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 ( Tph2 ), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.

PubMed

Jin, Xiangyuan; Uchiyama, Masateru; Zhang, Qi; Niimi, Masanori

2014-05-09

Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated. Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival. Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.

Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations.

PubMed

Beinfeld, Margery C; Blum, Alissa; Vishnuvardhan, Daesety; Fanous, Sanya; Marchand, James E

2005-11-18

Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain. To examine its role in cholecystokinin processing, cholecystokinin levels were measured in dissected brain regions from prohormone convertase 2 knock-out mice. Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice. In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type. Female mice were more affected by the loss of prohormone convertase 2 than male mice. The decrease in cholecystokinin levels in these brain regions shows that prohormone convertase 2 is important for cholecystokinin processing. Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression. They revealed that cholecystokinin and prohormone convertase 1 mRNA levels in cerebral cortex and olfactory bulb were actually lower in knock-out than wild type, whereas their expression in other brain regions of knock-out mouse brain was the same as wild type. Female mice frequently had higher expression of cholecystokinin and prohormone convertase 1, 2, and 5 mRNA than male mice. The loss of prohormone convertase 2 alters CCK processing in specific brain regions. This loss also appears to trigger compensatory mechanisms in cerebral cortex and olfactory bulb that produce elevated levels of cholecystokinin but do not involve increased expression of cholecystokinin, prohormone convertase 1 or 5 mRNA.

Evaluation of the Role of G Protein-Coupled Receptor Kinase 3 in Desensitization of Mouse Odorant Receptors in a Mammalian Cell Line and in Olfactory Sensory Neurons

PubMed Central

Kato, Aya; Reisert, Johannes; Ihara, Sayoko; Yoshikawa, Keiichi

2014-01-01

Thousands of odors are sensed and discriminated by G protein-coupled odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). G protein-coupled receptor kinases (GRKs) may have a role in desensitization of ORs. However, whether ORs are susceptible to agonist-dependent desensitization and whether GRKs affect odorant responsiveness of OSNs are currently unknown. Here we show that GRK3 attenuated the agonist responsiveness of a specific mouse odorant receptor for eugenol (mOR-EG) upon agonist pretreatment in HEK293 cells, but GRK3 did not affect the response amplitude or the recovery kinetics upon repeated agonist stimulation. We performed electrophysiological recordings of single OSNs which expressed mOR-EG and green fluorescent protein (GFP) in the presence or absence of GRK3. The kinetics and amplitude of agonist responsiveness of individual GFP-labeled mOR-EG neurons were not significantly affected by the absence of GRK3. These results indicate that the role of GRK3 in attenuating ORs responsiveness in OSNs may have been overestimated. PMID:25313015

Impact of the Usher syndrome on olfaction.

PubMed

Jansen, Fabian; Kalbe, Benjamin; Scholz, Paul; Mikosz, Marta; Wunderlich, Kirsten A; Kurtenbach, Stefan; Nagel-Wolfrum, Kerstin; Wolfrum, Uwe; Hatt, Hanns; Osterloh, Sabrina

2016-02-01

Usher syndrome is a genetically and clinically heterogeneous disease in humans, characterized by sensorineural hearing loss, retinitis pigmentosa and vestibular dysfunction. This disease is caused by mutations in genes encoding proteins that form complex networks in different cellular compartments. Currently, it remains unclear whether the Usher proteins also form networks within the olfactory epithelium (OE). Here, we describe Usher gene expression at the mRNA and protein level in the OE of mice and showed interactions between these proteins and olfactory signaling proteins. Additionally, we analyzed the odor sensitivity of different Usher syndrome mouse models using electro-olfactogram recordings and monitored significant changes in the odor detection capabilities in mice expressing mutant Usher proteins. Furthermore, we observed changes in the expression of signaling proteins that might compensate for the Usher protein deficiency. In summary, this study provides novel insights into the presence and purpose of the Usher proteins in olfactory signal transduction. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels

PubMed Central

Kapoor, Vikrant; Provost, Allison; Agarwal, Prateek; Murthy, Venkatesh N.

2015-01-01

The serotonergic raphe nuclei are involved in regulating brain states over time-scales of minutes and hours. We examined more rapid effects of serotonergic activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation, similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels. PMID:26752161

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

PubMed Central

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors. PMID:28066196

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

PubMed

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors.

Differential effects of unilateral olfactory deprivation on noradrenergic and cholinergic systems in the main olfactory bulb of the rat.

PubMed

Gómez, C; Briñón, J G; Colado, M I; Orio, L; Vidal, M; Barbado, M V; Alonso, J R

2006-09-15

The lack of environmental olfactory stimulation produced by sensory deprivation causes significant changes in the deprived olfactory bulb. Olfactory transmission in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems. The present report examines the effects of unilateral deprivation on the noradrenergic and cholinergic centrifugal systems innervating the MOB. The morphology, distribution, and density of positive axons were studied in the MOBs of control and deprived rats, using dopamine-beta-hydroxylase (DBH)-immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial sections. Catecholamine content was compared among the different groups of MOBs (control, contralateral, and ipsilateral to the deprivation) using high-performance liquid chromatography analysis. Sensory deprivation revealed that the noradrenergic system developed adaptive plastic changes after olfactory deprivation, including important modifications in its fiber density and distribution, while no differences in cholinergic innervation were observed under the same conditions. The noradrenergic system underwent an important alteration in the glomerular layer, in which some glomeruli showed a dense noradrenergic innervation that was not detected in control animals. The DBH-positive glomeruli with the highest noradrenergic fiber density were compared with AChE-stained sections and it was observed that the strongly noradrenergic-innervated glomeruli were always atypical glomeruli (characterized by their strong degree of cholinergic innervation). In addition to the morphological findings, our biochemical data revealed that olfactory deprivation caused a decrease in the content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ipsilateral MOB in comparison to the contralateral and control MOBs, together with an increase in noradrenaline levels in both the ipsilateral and contralateral MOBs. Our results show that regulation of the noradrenergic centrifugal system in the MOB depends on environmental olfactory stimulation and that it is highly reactive to sensory deprivation. By contrast, the cholinergic system is fairly stable and does not exhibit clear changes after the loss of sensory inputs.

Neurodegeneration and Vision Loss after Mild Blunt Trauma in the C57Bl/6 and DBA/2J Mouse

PubMed Central

Bricker-Anthony, Courtney; Rex, Tonia S.

2015-01-01

Damage to the eye from blast exposure can occur as a result of the overpressure air-wave (primary injury), flying debris (secondary injury), blunt force trauma (tertiary injury), and/or chemical/thermal burns (quaternary injury). In this study, we investigated damage in the contralateral eye after a blast directed at the ipsilateral eye in the C57Bl/6J and DBA/2J mouse. Assessments of ocular health (gross pathology, electroretinogram recordings, optokinetic tracking, optical coherence tomography and histology) were performed at 3, 7, 14 and 28 days post-trauma. Olfactory epithelium and optic nerves were also examined. Anterior pathologies were more common in the DBA/2J than in the C57Bl/6 and could be prevented with non-medicated viscous eye drops. Visual acuity decreased over time in both strains, but was more rapid and severe in the DBA/2J. Retinal cell death was present in approximately 10% of the retina at 7 and 28 days post-blast in both strains. Approximately 60% of the cell death occurred in photoreceptors. Increased oxidative stress and microglial reactivity was detected in both strains, beginning at 3 days post-injury. However, there was no sign of injury to the olfactory epithelium or optic nerve in either strain. Although our model directs an overpressure air-wave at the left eye in a restrained and otherwise protected mouse, retinal damage was detected in the contralateral eye. The lack of damage to the olfactory epithelium and optic nerve, as well as the different timing of cell death as compared to the blast-exposed eye, suggests that the injuries were due to physical contact between the contralateral eye and the housing chamber of the blast device and not propagation of the blast wave through the head. Thus we describe a model of mild blunt eye trauma. PMID:26148200

Maternal odours induce Fos in the main but not the accessory olfactory bulbs of neonatal male and female ferrets.

PubMed

Chang, Y M; Kelliher, K R; Baum, M J

2001-06-01

Previous research demonstrated that exposing gonadectomized adult ferrets to odours in oestrous female bedding induced nuclear Fos-immunoreactivity (Fos-IR; a marker of neuronal activity) in the main as opposed to the accessory olfactory system in a sexually dimorphic fashion, which was further augmented in both sexes by treatment with testosterone propionate. Ferrets are born in an altricial state and presumably use maternal odour cues to locate the nipples until the eyes open after postnatal (P) day 23. We investigated whether maternal odours augment neuronal Fos preferentially in the main versus accessory olfactory system of neonatal male and female ferret kits. Circulating testosterone levels peak in male ferrets on postnatal day P15, and mothers provide maximal anogenital stimulation (AGS) to males at this same age. Therefore, we assessed the ability of maternal odours to augment Fos-IR in the accessory olfactory bulb (AOB), the main olfactory bulb (MOB) and other forebrain regions of male and female ferret kits on P15 and investigated whether artificial AGS (provided with a paintbrush) would further enhance any effects of maternal odours. After separation from their mothers for 4 h, groups of male and female kits that were placed for 1.5 h with their anaesthetized mother had significantly more Fos-IR cells in the MOB granule cell layer and in the anterior-cortical amygdala, but not in the AOB cell layer, compared to control kits that were left on the heating pad. Artificial AGS failed to amplify these effects of maternal odours. Maternal odours (with or without concurrent AGS) failed to augment neuronal Fos-IR in medial amygdaloid and hypothalamic regions that are activated in adult ferrets by social odours. In neonatal ferrets of both sexes, as in adults, socially relevant odours are detected by the main olfactory epithelium and initially processed by the MOB and the anterior-cortical amygdala. In neonates, unlike adults, medial amygdaloid and hypothalamic neurones either do not respond to these inputs or respond in a manner that fails to induce Fos expression.

Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

PubMed Central

Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

2013-01-01

Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

A direct main olfactory bulb projection to the ‘vomeronasal’ amygdala in female mice selectively responds to volatile pheromones from males

PubMed Central

Kang, Ningdong; Baum, Michael J.; Cherry, James A.

2009-01-01

The main olfactory system, like the accessory olfactory system, responds to pheromones involved in social communication. Whereas pheromones detected by the accessory system are transmitted to the hypothalamus via the medial (‘vomeronasal’) amygdala, the pathway by which pheromones are detected and transmitted by the main system is not well understood. We examined in female mice whether a direct projection from mitral/tufted (M/T) cells in the main olfactory bulb (MOB) to the medial amygdala exists, and whether medial amygdala-projecting M/T cells are activated by volatile urinary odors from conspecifics or a predator (cat). Simultaneous anterograde tracing using Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby placed in the MOB and accessory olfactory bulb (AOB), respectively, revealed that axons of MOB M/T cells projected to superficial laminae of layer Ia in anterior and posterodorsal subdivisions of the medial amygdala, whereas projection neurons from the AOB sent axons to non-overlapping, deeper layer Ia laminae of the same subdivisions. Placement of the retrograde tracer cholera toxin B into the medial amygdala labeled M/T cells that were concentrated in the ventral MOB. Urinary volatiles from male mice, but not from female conspecifics or cat, induced Fos in medial amygdala-projecting MOB M/T cells of female subjects, suggesting that information about male odors is transmitted directly from the MOB to the ‘vomeronasal’ amygdala. The presence of a direct MOB-to-medial amygdala pathway in mice and other mammals could enable volatile, opposite-sex pheromones to gain privileged access to diencephalic structures that control mate recognition and reproduction. PMID:19187265

Changes in the serotonergic system and in brain-derived neurotrophic factor distribution in the main olfactory bulb of pcd mice before and after mitral cell loss.

PubMed

Gómez, C; Curto, G G; Baltanás, F C; Valero, J; O'Shea, E; Colado, M I; Díaz, D; Weruaga, E; Alonso, J R

2012-01-10

The serotonergic centrifugal system innervating the main olfactory bulb (MOB) plays a key role in the modulation of olfactory processing. We have previously demonstrated that this system suffers adaptive changes under conditions of a lack of olfactory input. The present work examines the response of this centrifugal system after mitral cell loss in the Purkinje cell degeneration (pcd) mutant mice. The distribution and density of serotonergic centrifugal axons were studied in the MOB of control and pcd mice, both before and after the loss of mitral cells, using serotonin (5-HT) and 5-HT transporter immunohistochemistry. Studies of the amount of 5-HT and its metabolite, 5-hydroxyindole acetic acid (5-HIAA), were performed by means of high-performance liquid chromatography (HPLC), and the relative amounts of brain-derived neurotrophin factor, BDNF, and its major receptor, tropomyosin-related kinase B (TrkB), were measured by Western blot. Our study revealed that the serotonergic system develops adaptive changes after, but not before, mitral cell loss. The lack of the main bulbar projection cells causes a decrease in the serotonergic input received by the MOB, whereas the number of serotonergic cells in the raphe nuclei remains constant. In addition, one of the molecules directly involved in serotonergic sprouting, the neurotrophin BDNF and its main receptor TrkB, underwent alterations in the MOBs of the pcd animals even before the loss of mitral cells. These data indicate that serotonergic function in the MOB is closely related to olfactory activity and that mitral cell loss induces serotonergic plastic responses. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers.

PubMed

Laska, M; Shepherd, G M

2007-01-05

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species' olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers

PubMed Central

Laska, Matthias; Shepherd, Gordon M.

2006-01-01

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species′ olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships. PMID:17045753

Impaired olfaction in mice lacking aquaporin-4 water channels.

PubMed

Lu, Daniel C; Zhang, Hua; Zador, Zsolt; Verkman, A S

2008-09-01

Aquaporin-4 (AQP4) is a water-selective transport protein expressed in glial cells throughout the central nervous system. AQP4 deletion in mice produces alterations in several neuroexcitation phenomena, including hearing, vision, epilepsy, and cortical spreading depression. Here, we report defective olfaction and electroolfactogram responses in AQP4-null mice. Immunofluorescence indicated strong AQP4 expression in supportive cells of the nasal olfactory epithelium. The olfactory epithelium in AQP4-null mice had identical appearance, but did not express AQP4, and had approximately 12-fold reduced osmotic water permeability. Behavioral analysis showed greatly impaired olfaction in AQP4-null mice, with latency times of 17 +/- 0.7 vs. 55 +/- 5 s in wild-type vs. AQP4-null mice in a buried food pellet test, which was confirmed using an olfactory maze test. Electroolfactogram voltage responses to multiple odorants were reduced in AQP4-null mice, with maximal responses to triethylamine of 0.80 +/- 0.07 vs. 0.28 +/- 0.03 mV. Similar olfaction and electroolfactogram defects were found in outbred (CD1) and inbred (C57/bl6) mouse genetic backgrounds. Our results establish AQP4 as a novel determinant of olfaction, the deficiency of which probably impairs extracellular space K(+) buffering in the olfactory epithelium.

Human Neural Cells Transiently Express Reelin during Olfactory Placode Development

PubMed Central

Antal, M. Cristina; Samama, Brigitte; Ghandour, M. Said; Boehm, Nelly

2015-01-01

Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

Olfactory stimulation modulates the blood glucose level in rats.

PubMed

Tsuji, Tadataka; Tanaka, Susumu; Bakhshishayan, Sanam; Kogo, Mikihiko; Yamamoto, Takashi

2018-01-01

In both humans and animals, chemosensory stimuli, including odors and tastes, induce a variety of physiologic and mental responses related to energy homeostasis, such as glucose kinetics. The present study examined the importance of olfactory function in glucose kinetics following ingestion behavior in a simplified experimental scenario. We applied a conventional glucose tolerance test to rats with and without olfactory function and analyzed subsequent blood glucose (BG) curves in detail. The loss of olfactory input due to experimental damage to the olfactory mucosa induced a marked decrease in the area under the BG curve. Exposure to grapefruit odor and its main component, limonene, both of which activate the sympathetic nerves, before glucose loading also greatly depressed the BG curve. Pre-loading exposure to lavender odor, a parasympathetic activator, stabilized the BG level. These results suggest that olfactory function is important for proper glucose kinetics after glucose intake and that certain fragrances could be utilized as tools for controlling BG levels.

Olfactory behavior and physiology are disrupted in prion protein knockout mice.

PubMed

Le Pichon, Claire E; Valley, Matthew T; Polymenidou, Magdalini; Chesler, Alexander T; Sagdullaev, Botir T; Aguzzi, Adriano; Firestein, Stuart

2009-01-01

The prion protein PrP(C) is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrP(C) rather than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp(-/-) mice were rescued by transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system.

Synchronized Activity in The Main and Accessory Olfactory Bulbs and Vomeronasal Amygdala Elicited by Chemical Signals in Freely Behaving Mice.

PubMed

Pardo-Bellver, Cecília; Martínez-Bellver, Sergio; Martínez-García, Fernando; Lanuza, Enrique; Teruel-Martí, Vicent

2017-08-30

Chemosensory processing in mammals involves the olfactory and vomeronasal systems, but how the activity of both circuits is integrated is unknown. In our study, we recorded the electrophysiological activity in the olfactory bulbs and the vomeronasal amygdala in freely behaving mice exploring a battery of neutral and conspecific stimuli. The exploration of stimuli, including a neutral stimulus, induced synchronic activity in the olfactory bulbs characterized by a dominant theta rhythmicity, with specific theta-gamma coupling, distinguishing between vomeronasal and olfactory structures. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in the nasal cavity and the vomeronasal pumping. In the amygdala, male stimuli are preferentially processed in the medial nucleus, whereas female cues induced a differential response in the posteromedial cortical amygdala. Thus, particular theta-gamma patterns in the olfactory network modulates the integration of chemosensory information in the amygdala, allowing the selection of an appropriate behaviour.

Progressive Pathological Changes in Neurochemical Profile of the Hippocampus and Early Changes in the Olfactory Bulbs of Tau Transgenic Mice (rTg4510).

PubMed

Kim, Jieun; Choi, In-Young; Duff, Karen E; Lee, Phil

2017-06-01

Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain. In this study, we measured alterations in a number of key neurochemicals associated with tauopathy-induced neurodegeneration in the hippocampus and the olfactory bulbs of a transgenic mouse model of FTLD-tauopathy, line rTg4510, using in vivo 1 H magnetic resonance spectroscopy at 9.4 T. The rTg4510 line develops tauopathy at a young age (4-5 months), reaching a severe stage by 8-12 months of age. Longitudinal measurement of neurochemical concentrations in the hippocampus of mice from 5 to 12 months of age showed significant progressive changes with distinctive disease staging patterns including N-acetylaspartate, myo-inositol, γ-aminobutyric acid, glutathione and glutamine. The accompanying hippocampal volume loss measured using magnetic resonance imaging showed significant correlation (p < 0.01) with neurochemical measurements. Neurochemical alterations in the olfactory bulbs were more pronounced than those in the hippocampus in rTg4510 mice. These results demonstrate progressive neuropathology in the mouse model and provide potential biomarkers of early neuropathological events and effective noninvasive monitoring of the disease progression and treatment efficacy, which can be easily translated to clinical studies.

Olfactory Processing in Male Children with Autism: Atypical Odor Threshold and Identification

ERIC Educational Resources Information Center

Muratori, Filippo; Tonacci, Alessandro; Billeci, Lucia; Catalucci, Tiziana; Igliozzi, Roberta; Calderoni, Sara; Narzisi, Antonio

2017-01-01

Sensory issues are of great interest in ASD diagnosis. However, their investigation is mainly based on external observation (parent reports), with methodological limitations. Unobtrusive olfactory assessment allows studying autism neurosensoriality. Here, 20 male children with high-functioning ASD and 20 matched controls were administered a…

Mechanism for Clastogenic Activity of Naphthalene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchholz, Bruce A.

2016-06-24

Naphthalene incubations form DNA adducts in vitro in a dose dependent manner in both mouse and rat tissues. Rodent tissue incubations with naphthalene indicate that naphthalene forms as many DNA adducts as Benzo(a)pyrene, a known DNA binding carcinogen. The mouse airway has the greatest number of DNA adducts, corresponding to the higher metabolic activation of naphthalene in this location. Both rat tissues, the rat olfactory (tumor target) and the airways (non-tumor target), have similar levels of NA-DNA adducts, indicating that short term measures of initial adduct formation do not directly correlate with sites of tumor formation in the NTP bioassays.

Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

PubMed

Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

2016-11-01

Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Direct nuclear magnetic resonance observation of odorant binding to mouse odorant receptor MOR244-3.

PubMed

Burger, Jessica L; Jeerage, Kavita M; Bruno, Thomas J

2016-06-01

Mammals are able to perceive and differentiate a great number of structurally diverse odorants through the odorant's interaction with odorant receptors (ORs), proteins found within the cell membrane of olfactory sensory neurons. The natural gas industry has used human olfactory sensitivity to sulfur compounds (thiols, sulfides, etc.) to increase the safety of fuel gas transport, storage, and use through the odorization of this product. In the United States, mixtures of sulfur compounds are used, but the major constituent of odorant packages is 2-methylpropane-2-thiol, also known as tert-butyl mercaptan. It has been fundamentally challenging to understand olfaction and odorization due to the low affinity of odorous ligands to the ORs and the difficulty in expressing a sufficient number of OR proteins. Here, we directly observed the binding of tert-butyl mercaptan and another odiferous compound, cis-cyclooctene, to mouse OR MOR244-3 on living cells by saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy. This effort lays the groundwork for resolving molecular mechanisms responsible for ligand binding and resulting signaling, which in turn will lead to a clearer understanding of odorant recognition and competition. Published by Elsevier Inc.

Structural basis for serotonergic regulation of neural circuits in the mouse olfactory bulb.

PubMed

Suzuki, Yoshinori; Kiyokage, Emi; Sohn, Jaerin; Hioki, Hiroyuki; Toida, Kazunori

2015-02-01

Olfactory processing is well known to be regulated by centrifugal afferents from other brain regions, such as noradrenergic, acetylcholinergic, and serotonergic neurons. Serotonergic neurons widely innervate and regulate the functions of various brain regions. In the present study, we focused on serotonergic regulation of the olfactory bulb (OB), one of the most structurally and functionally well-defined brain regions. Visualization of a single neuron among abundant and dense fibers is essential to characterize and understand neuronal circuits. We accomplished this visualization by successfully labeling and reconstructing serotonin (5-hydroxytryptamine: 5-HT) neurons by infection with sindbis and adeno-associated virus into dorsal raphe nuclei (DRN) of mice. 5-HT synapses were analyzed by correlative confocal laser microscopy and serial-electron microscopy (EM) study. To further characterize 5-HT neuronal and network function, we analyzed whether glutamate was released from 5-HT synaptic terminals using immuno-EM. Our results are the first visualizations of complete 5-HT neurons and fibers projecting from DRN to the OB with bifurcations. We found that a single 5-HT axon can form synaptic contacts to both type 1 and 2 periglomerular cells within a single glomerulus. Through immunolabeling, we also identified vesicular glutamate transporter 3 in 5-HT neurons terminals, indicating possible glutamatergic transmission. Our present study strongly implicates the involvement of brain regions such as the DRN in regulation of the elaborate mechanisms of olfactory processing. We further provide a structure basis of the network for coordinating or linking olfactory encoding with other neural systems, with special attention to serotonergic regulation. © 2014 Wiley Periodicals, Inc.

Hypothalamus-Olfactory System Crosstalk: Orexin A Immunostaining in Mice

PubMed Central

Gascuel, Jean; Lemoine, Aleth; Rigault, Caroline; Datiche, Frédérique; Benani, Alexandre; Penicaud, Luc; Lopez-Mascaraque, Laura

2012-01-01

It is well known that olfaction influences food intake, and conversely, that an individual’s nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway. In rats, orexin positive cells are concentrated strictly in the lateral hypothalamus, while their projections invade nearly the entire brain including the olfactory system. Therefore, orexin appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways. So far, orexin has been described in rats, however, there is still a lack of information concerning its expression in the brains of adult and developing mice. In this context, we revisited the orexin A pattern in adult and developing mice using immunohistological methods and confocal microscopy. Besides minor differences, orexin A immunostaining in mice shares many features with those observed in rats. In the olfactory bulb, even though there are few orexin projections, they reach all the different layers of the olfactory bulb. In contrast to the presence of orexin projections in the main olfactory bulb, almost none have been found in the accessory olfactory bulb. The developmental expression of orexin A supports the hypothesis that orexin expression only appears post-natally. PMID:23162437

Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABAARs in the Hippocampus in Early Postnatal Sprague Dawley Rats.

PubMed

Zheng, Xiaomin; Liang, Liang; Hei, Changchun; Yang, Wenjuan; Zhang, Tingyuan; Wu, Kai; Qin, Yi; Chang, Qing

2018-04-17

Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5 μl) or saline (sham, 5 μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n = 6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P < 0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P < 0.01) and increased levels of learned helplessness (P < 0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABA A receptor alpha5 subunit (α5GABA A R) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P < 0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.

Adiponectin Enhances the Responsiveness of the Olfactory System

PubMed Central

Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

2013-01-01

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

Pheromone detection by mammalian vomeronasal neurons.

PubMed

Zufall, Frank; Kelliher, Kevin R; Leinders-Zufall, Trese

2002-08-01

The vomeronasal organ (VNO) of mammals plays an essential role in the perception of chemical stimuli of social nature including pheromone-like signals but direct evidence for the transduction of pheromones by vomeronasal sensory neurons has been lacking. The recent development of electrophysiological and optical imaging methods using confocal microscopy has enabled researchers to systematically analyze sensory responses in large populations of mouse vomeronasal neurons. These experiments revealed that vomeronasal neurons are surprisingly sensitive and highly discriminative detectors of volatile, urinary metabolites that have pheromonal activity in recipient mice. Functional mapping studies of pheromone receptor activation have uncovered the basic principles of sensory processing by vomeronasal neurons and revealed striking differences in the neural mechanisms by which chemosensory information is detected by receptor neurons in the VNO and the main olfactory epithelium. These advances offer the opportunity to decipher the logic of mammalian pheromonal communication. Copyright 2002 Wiley-Liss, Inc.

Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

PubMed Central

Knaus, Hans‐Günther; Schwarzer, Christoph

2015-01-01

ABSTRACT The sodium‐activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high‐conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093–2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26587966

Combined Memantine and Donepezil Treatment Improves Behavioral and Psychological Symptoms of Dementia-Like Behaviors in Olfactory Bulbectomized Mice.

PubMed

Yabuki, Yasushi; Matsuo, Kazuya; Hirano, Koga; Shinoda, Yasuharu; Moriguchi, Shigeki; Fukunaga, Kohji

2017-01-01

Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed. Here, we investigate combined memantine/donepezil effects on cognitive impairment and BPSD-like behaviors in olfactory bulbectomized (OBX) mice. Interestingly, combined administration synergistically improved both depressive-like behaviors and impaired social interaction in OBX mice, whereas only weak synergistic effects on cognitive performance were seen. To address mechanisms underlying these effects, we used in vivo microdialysis study and observed impaired nicotine-induced serotonin (5-HT) release in OBX mouse hippocampus. Combined memantine/donepezil administration, but not single administration of either, significantly antagonized the decrease in nicotine-induced 5-HT release seen in OBX mouse hippocampus. Furthermore, decreased autophosphorylation of calcium/calmodulin dependent protein kinase II (CaMKII) was rescued in hippocampal CA1 and dentate gyrus of OBX mice by combined memantine/donepezil administration. These results suggest that improvement of BPSD-like behaviors by the co-administration of both drugs is in part mediated by enhanced 5-HT release and CaMKII activity in OBX mouse hippocampus. © 2016 S. Karger AG, Basel.

TC-83 vaccine protects against airborne or subcutaneous challenge with heterologous mouse-virulent strains of Venezuelan equine encephalitis virus.

PubMed

Phillpotts, R J; Wright, A J

1999-02-26

Vaccination with TC-83 virus produced solid protection against subcutaneous challenge with Venezuelan equine encephalitis (VEEV) viruses from homologous and heterologous serogroups, but breakthrough infection and disease occurred after airborne challenge. Breakthrough occurred more often with time after vaccination, and was more frequent with epizootic, homologous serogroup 1A/B viruses than with enzootic, heterologous serogroup viruses. A decrease in VEEV-specific IgA levels in the respiratory tract of vaccinated mice may explain the increased frequency of breakthrough with time after vaccination. However increased breakthrough with the highly virulent homologous serogroup 1A/B viruses (compared to less virulent viruses from heterologous serogroups) may be a consequence of their greater ability to invade the brain via the olfactory neuroepithelium and olfactory nerve.

Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium.

PubMed

Tucker, Eric S; Lehtinen, Maria K; Maynard, Tom; Zirlinger, Mariela; Dulac, Catherine; Rawson, Nancy; Pevny, Larysa; Lamantia, Anthony-Samuel

2010-08-01

Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes - olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic precursors that express high levels of Sox2 and Ascl1. Precursors expressing high levels of Meis genes primarily reside in the lateral OE, whereas precursors expressing high levels of Sox2 and Ascl1 primarily reside in the medial OE. Fgf8 maintains these expression signatures and proliferative identities. Using electroporation in the wild-type embryonic OE in vitro as well as Fgf8, Sox2 and Ascl1 mutant mice in vivo, we found that Sox2 dose and Meis1 - independent of Pbx co-factors - regulate Ascl1 expression and the transition from lateral to medial precursor state. Thus, we have identified proliferative characteristics and a dose-dependent transcriptional network that define distinct OE precursors: medial precursors that are most probably transit amplifying neurogenic progenitors for ORNs, VRNs and GnRH neurons, and lateral precursors that include multi-potent self-renewing OE neural stem cells.

Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium

PubMed Central

Tucker, Eric S.; Lehtinen, Maria K.; Maynard, Tom; Zirlinger, Mariela; Dulac, Catherine; Rawson, Nancy; Pevny, Larysa; LaMantia, Anthony-Samuel

2010-01-01

Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes – olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic precursors that express high levels of Sox2 and Ascl1. Precursors expressing high levels of Meis genes primarily reside in the lateral OE, whereas precursors expressing high levels of Sox2 and Ascl1 primarily reside in the medial OE. Fgf8 maintains these expression signatures and proliferative identities. Using electroporation in the wild-type embryonic OE in vitro as well as Fgf8, Sox2 and Ascl1 mutant mice in vivo, we found that Sox2 dose and Meis1 – independent of Pbx co-factors – regulate Ascl1 expression and the transition from lateral to medial precursor state. Thus, we have identified proliferative characteristics and a dose-dependent transcriptional network that define distinct OE precursors: medial precursors that are most probably transit amplifying neurogenic progenitors for ORNs, VRNs and GnRH neurons, and lateral precursors that include multi-potent self-renewing OE neural stem cells. PMID:20573694

Impaired olfaction in mice lacking aquaporin-4 water channels

PubMed Central

Lu, Daniel C.; Zhang, Hua; Zador, Zsolt; Verkman, A. S.

2008-01-01

Aquaporin-4 (AQP4) is a water-selective transport protein expressed in glial cells throughout the central nervous system. AQP4 deletion in mice produces alterations in several neuroexcitation phenomena, including hearing, vision, epilepsy, and cortical spreading depression. Here, we report defective olfaction and electroolfactogram responses in AQP4-null mice. Immunofluorescence indicated strong AQP4 expression in supportive cells of the nasal olfactory epithelium. The olfactory epithelium in AQP4-null mice had identical appearance, but did not express AQP4, and had ∼12-fold reduced osmotic water permeability. Behavioral analysis showed greatly impaired olfaction in AQP4-null mice, with latency times of 17 ± 0.7 vs. 55 ± 5 s in wild-type vs. AQP4-null mice in a buried food pellet test, which was confirmed using an olfactory maze test. Electroolfactogram voltage responses to multiple odorants were reduced in AQP4-null mice, with maximal responses to triethylamine of 0.80 ± 0.07 vs. 0.28 ± 0.03 mV. Similar olfaction and electroolfactogram defects were found in outbred (CD1) and inbred (C57/bl6) mouse genetic backgrounds. Our results establish AQP4 as a novel determinant of olfaction, the deficiency of which probably impairs extracellular space K+ buffering in the olfactory epithelium.—Lu, D. C., Zhang, H., Zador, Z., Verkman, A. S. Impaired olfaction in mice lacking aquaporin-4 water channels. PMID:18511552

Male hamster copulatory responses to a high molecular weight fraction of vaginal discharge: effects of vomeronasal organ removal.

PubMed

Clancy, A N; Macrides, F; Singer, A G; Agosta, W C

1984-10-01

The importance of the vomeronasal (accessory olfactory) system for the copulatory responses of male hamsters to a high molecular weight fraction (HMF) of vaginal discharge was assessed in animals that had their vomeronasal organs (VNO) removed. These organs were extirpated bilaterally using an oral approach through the palate so as to eliminate the peripheral afferents to the accessory olfactory bulb (AOB) with minimal or no damage to the main olfactory system. The selective peripheral deafferentation procedure was verified by applying horseradish peroxidase intranasally following intraperitoneal injections of epinephrine to facilitate the vomeronasal pumping mechanism that draws fluids into the VNO. Heavy, bilateral anterograde labeling was evident in the olfactory nerve afferents within the main olfactory bulb of males that had their VNO removed and of animals that received sham surgery. Sham-operated males also had heavy, bilateral labeling in the vomeronasal nerve afferents within the AOB, whereas no such labeling occurred among animals with bilateral removal of the VNO. In sham-operated animals, both the HMF and the unfractionated discharge significantly increased the incidence of intromission attempts toward anesthetized males (surrogate females) whose hindquarters were scented with these stimuli. The unfractionated discharge also produced a significant elevation of overt copulatory behavior in males with selective peripheral deafferentation of the vomeronasal system, whereas the HMF did not facilitate copulatory behavior in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo binding of /sup 125/I-LSD to serotonin 5-HT/sub 2/ receptors in mouse brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartig, P.R.; Scheffel, U., Frost, J.J.; Wagner, H.N. Jr.

The binding of /sup 125/I-LSD (2-(/sup 125/I)-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of /sup 125/I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of /sup 125/I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of /sup 125/I-LSD.more » Serotonergic compounds potently inhibited /sup 125/I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that /sup 125/I-LSD labels serotonin 5-HT/sub 2/ receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, /sup 125/I-LSD labeling occurs predominantly or entirely at serotonic 5-HT/sub 2/ sites. In the striatum, /sup 125/I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that /sup 125/I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT/sub 2/ receptors in the mammalian cortex.« less

[Deficits in medical counseling in olfactory dysfunction].

PubMed

Haxel, B R; Nisius, A; Fruth, K; Mann, W J; Muttray, A

2012-05-01

Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Fang; Fang, Cheng; School of Public Health, State University of New York at Albany, NY 12201

We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasalmore » cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels. • Dexamethasone inhibits DCBN-induced IL-6 production, but not the stem cell loss.« less

Olfactory receptor antagonism between odorants

PubMed Central

Oka, Yuki; Omura, Masayo; Kataoka, Hiroshi; Touhara, Kazushige

2004-01-01

The detection of thousands of volatile odorants is mediated by several hundreds of different G protein-coupled olfactory receptors (ORs). The main strategy in encoding odorant identities is a combinatorial receptor code scheme in that different odorants are recognized by different sets of ORs. Despite increasing information on agonist–OR combinations, little is known about the antagonism of ORs in the mammalian olfactory system. Here we show that odorants inhibit odorant responses of OR(s), evidence of antagonism between odorants at the receptor level. The antagonism was demonstrated in a heterologous OR-expression system and in single olfactory neurons that expressed a given OR, and was also visualized at the level of the olfactory epithelium. Dual functions of odorants as an agonist and an antagonist to ORs indicate a new aspect in the receptor code determination for odorant mixtures that often give rise to novel perceptual qualities that are not present in each component. The current study also provides insight into strategies to modulate perceived odorant quality. PMID:14685265

[Conjugated variability of spontaneous activity and behavioral response to olfactory stimuli in the taiga tick (Ixodes persulcatus)].

PubMed

Romashchenko, A V; Shnaĭder, E P; Petrovskiĭ, D V; Moshkin, M P

2013-01-01

According to -the automatic tracing of the movement of ticks in a Petri dish, motivational variability of the spontaneous activity and behavioral response of the taiga tick to olfactory stimuli was analyzed. In the studied sample, two groups of ticks that differ in the movement trajectory in the absence of stimulus were isolated, including ticks that mainly moved on the edge of the dish at maximum accessible height (group 1) and ticks that mainly moved at the bottom and wall of the dish (group 2). It was registered that ticks of group 1 (as opposed to ticks of group 2) demonstrated a pronounced behavioral response to olfactory stimuli (human synthetic pheromones and ammonia) and negative geotaxis. It was established that belonging to these groups depended On the time of day when the testing was performed and did not depend on the physiological age and infectious status.

Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei

PubMed Central

Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T.

2016-01-01

Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo. Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1–4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. SIGNIFICANCE STATEMENT Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory information by the olfactory bulb, an obligatory relay between sensory neurons and cortex. We find that serotonergic projections from the raphe nuclei to the olfactory bulb dramatically enhance the responses of two classes of inhibitory interneurons to sensory input, that this effect is mediated by increased glutamatergic drive onto these neurons, and that serotonergic afferent activation alters the responses of olfactory bulb output neurons in vivo. These results elucidate pathways by which neuromodulatory systems can dynamically regulate brain circuits during behavior. PMID:27335411

Initiation of olfactory placode development and neurogenesis is blocked in mice lacking both Six1 and Six4.

PubMed

Chen, Binglai; Kim, Eun-Hee; Xu, Pin-Xian

2009-02-01

Mouse olfactory epithelium (OE) originates from ectodermally derived placode, the olfactory placode that arises at the anterior end of the neural plate. Tissue grafting and recombination experiments suggest that the placode is derived from a common preplacodal domain around the neural plate and its development is directed by signals arising from the underlying mesoderm and adjacent neuroectoderm. In mice, loss of Six1 affects OE morphogenesis but not placode formation. We show here that embryos lacking both Six1 and Six4 failed to form the olfactory placode but the preplacodal region appeared to be specified as judged by the expression of Eya2, which marks the common preplacodal domain, suggesting a synergistic requirement of Six1 and Six4 in patterning the preplacodal ectoderm to a morphologic placode. Our results show that Six1 and Six4 are coexpressed in the preplacodal ectoderm from E8.0. In the olfactory pit, Six4 expression was observed in the peripheral precursors that overlap with Mash1-expressing cells, the early committed neuronal lineage. In contrast, Six1 is highly distributed in the peripheral regions where stem cells reside at E10.5 and it overlaps with Sox2 expression. Both genes are expressed in the basal and apical neuronal progenitors in the OE. Analyses of Six1;Six4 double mutant embryos demonstrated that the slightly thickened epithelium observed in the mutant was not induced for neuronal development. In contrast, in Six1(-/-) embryos, all neuronal lineage markers were initially expressed but the pattern of their expression was altered. Although very few, the pioneer neurons were initially present in the Six1 mutant OE. However, neurogenesis ceased by E12.5 due to markedly increased cell apoptosis and reduced proliferation, thus defining the cellular defects occurring in Six1(-/-) OE that have not been previously observed. Our findings demonstrate that Six1/4 function at the top of early events controlling olfactory placode formation and neuronal development. Our analyses show that the threshold of Six1/4 may be crucial for the expression of olfactory specific genes and that Six1 and Six4 may act synergistically to mediate olfactory placode specification and patterning through Fgf and Bmp signaling pathways.

Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

PubMed

Herrera, Loren P; Casas, Carlos E; Bates, Margaret L; Guest, James D

2005-08-08

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates.

Of pheromones and kairomones: what receptors mediate innate emotional responses?

PubMed

Fortes-Marco, Lluis; Lanuza, Enrique; Martinez-Garcia, Fernando

2013-09-01

Some chemicals elicit innate emotionally laden behavioral responses. Pheromones mediate sexual attraction, parental care or agonistic confrontation, whereas predators' kairomones elicit defensive behaviors in their preys. This essay explores the hypothesis that the detection of these semiochemicals relies on highly specific olfactory and/or vomeronasal receptors. The V1R, V2R, and formyl-peptide vomeronasal receptors bind their ligands in highly specific and sensitive way, thus being good candidates for pheromone- or kairomone-detectors (e.g., secreted and excreted proteins, peptides and lipophilic volatiles). The olfactory epithelium also expresses specific receptors, for example trace amine-associated receptors (TAAR) and guanylyl cyclase receptors (GC-D and other types), some of which bind kairomones and putative pheromones. However, most of the olfactory neurons express canonical olfactory receptors (ORs) that bind many ligands with different affinity, being not suitable for mediating responses to pheromones and kairomones. In this respect, trimethylthiazoline (TMT) is considered a fox-derived kairomone for mice and rats, but it seems to be detected by canonical ORs. Therefore, we have reassessed the kairomonal nature of TMT by analyzing the behavioral responses of outbred (CD1) and inbred mice (C57BL/J6) to TMT. Our results confirm that both mouse strains avoid TMT, which increases immobility in C57BL/J6, but not CD1 mice. However, mice of both strains sniff at TMT throughout the test and show no trace of TMT-induced contextual conditioning (immobility or avoidance). This suggests that TMT is not a kairomone but, similar to a loud noise, in high concentrations it induces aversion and stress as unspecific responses to a strong olfactory stimulation. Copyright © 2013 Wiley Periodicals, Inc.

Tbr2 Deficiency in Mitral and Tufted Cells Disrupts Excitatory–Inhibitory Balance of Neural Circuitry in the Mouse Olfactory Bulb

PubMed Central

Mizuguchi, Rumiko; Naritsuka, Hiromi; Mori, Kensaku; Mao, Chai-An; Klein, William H.; Yoshihara, Yoshihiro

2013-01-01

The olfactory bulb (OB) is the first relay station in the brain where odor information from the olfactory epithelium is integrated, processed through its intrinsic neural circuitry, and conveyed to higher olfactory centers. Compared with profound mechanistic insights into olfactory axon wiring from the nose to the OB, little is known about the molecular mechanisms underlying the formation of functional neural circuitry among various types of neurons inside the OB. T-box transcription factor Tbr2 is expressed in various types of glutamatergic excitatory neurons in the brain including the OB projection neurons, mitral and tufted cells. Here we generated conditional knockout mice in which the Tbr2 gene is inactivated specifically in mitral and tufted cells from late embryonic stages. Tbr2 deficiency caused cell-autonomous changes in molecular expression including a compensatory increase of another T-box member, Tbr1, and a concomitant shift of vesicular glutamate transporter (VGluT) subtypes from VGluT1 to VGluT2. Tbr2-deficient mitral and tufted cells also exhibited anatomical abnormalities in their dendritic morphology and projection patterns. Additionally, several non-cell-autonomous phenotypes were observed in parvalbumin-, calbindin-, and 5T4-positive GABAergic interneurons. Furthermore, the number of dendrodendritic reciprocal synapses between mitral/tufted cells and GABAergic interneurons was significantly reduced. Upon stimulation with odorants, larger numbers of mitral and tufted cells were activated in Tbr2 conditional knockout mice. These results suggest that Tbr2 is required for not only the proper differentiation of mitral and tufted cells, but also for the establishment of functional neuronal circuitry in the OB and maintenance of excitatory–inhibitory balance crucial for odor information processing. PMID:22745484

Tbr2 deficiency in mitral and tufted cells disrupts excitatory-inhibitory balance of neural circuitry in the mouse olfactory bulb.

PubMed

Mizuguchi, Rumiko; Naritsuka, Hiromi; Mori, Kensaku; Mao, Chai-An; Klein, William H; Yoshihara, Yoshihiro

2012-06-27

The olfactory bulb (OB) is the first relay station in the brain where odor information from the olfactory epithelium is integrated, processed through its intrinsic neural circuitry, and conveyed to higher olfactory centers. Compared with profound mechanistic insights into olfactory axon wiring from the nose to the OB, little is known about the molecular mechanisms underlying the formation of functional neural circuitry among various types of neurons inside the OB. T-box transcription factor Tbr2 is expressed in various types of glutamatergic excitatory neurons in the brain including the OB projection neurons, mitral and tufted cells. Here we generated conditional knockout mice in which the Tbr2 gene is inactivated specifically in mitral and tufted cells from late embryonic stages. Tbr2 deficiency caused cell-autonomous changes in molecular expression including a compensatory increase of another T-box member, Tbr1, and a concomitant shift of vesicular glutamate transporter (VGluT) subtypes from VGluT1 to VGluT2. Tbr2-deficient mitral and tufted cells also exhibited anatomical abnormalities in their dendritic morphology and projection patterns. Additionally, several non-cell-autonomous phenotypes were observed in parvalbumin-, calbindin-, and 5T4-positive GABAergic interneurons. Furthermore, the number of dendrodendritic reciprocal synapses between mitral/tufted cells and GABAergic interneurons was significantly reduced. Upon stimulation with odorants, larger numbers of mitral and tufted cells were activated in Tbr2 conditional knockout mice. These results suggest that Tbr2 is required for not only the proper differentiation of mitral and tufted cells, but also for the establishment of functional neuronal circuitry in the OB and maintenance of excitatory-inhibitory balance crucial for odor information processing.

The optimal evaluation and management of patients with a gradual onset of olfactory loss.

PubMed

Enriquez, Karla; Lehrer, Eduardo; Mullol, Joaquim

2014-02-01

The aim of this review is to provide an overview of the causes of olfactory dysfunction, their evaluation and management, with a main focus on the gradual/progressive loss of smell. As the sense of smell gives us essential information about our environment, its loss can cause nutritional and social problems while threatening an individual's safety. Recent surveys have shown quite a substantial prevalence of hyposmia (one out of four people) and anosmia (one out of 200 people) in a variety of populations. Nasal inflammatory diseases such as allergic rhinitis and predominantly chronic rhinosinusitis account for the major and common causes of gradual/progressive loss of smell. However, they are also among the most successfully treated forms of olfactory dysfunction. The management of gradual/progressive smell deficit must always address its etiological causes. In most cases, a detailed medical history and nasal examination, smell testing, and imaging will help to establish an appropriate diagnosis. In addition to anti-inflammatory therapy, mainly nasal and systemic corticosteroids, recent investigations on smell training suggest that the controlled exposure to selected odors may increase olfactory performance. See the Video Supplementary Digital Content 1 (http://links.lww.com/COOH/A8).

Chemosensory event-related potentials in relation to side of stimulation, age, sex, and stimulus concentration.

PubMed

Stuck, B A; Frey, S; Freiburg, C; Hörmann, K; Zahnert, T; Hummel, T

2006-06-01

For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were recorded; stimuli were presented in different concentrations to the left and right nostril. Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor 'sex' for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to chemosensory stimuli are related to sex, while the side of stimulation does not play a major role in the presently used paradigm. Finally, these data establish the lateralization paradigm as a psychophysical tool to investigate intranasal trigeminal function. The present results obtained in a representative group of healthy subjects establishes a comprehensive set of data, which will serve as reference for future work in this area of research.

Organisation and tyrosine hydroxylase and calretinin immunoreactivity in the main olfactory bulb of paca (Cuniculus paca): a large caviomorph rodent.

PubMed

Sasahara, Tais Harumi de Castro; Leal, Leonardo Martins; Spillantini, Maria Grazia; Machado, Márcia Rita Fernandes

2015-04-01

The majority of neuroanatomical and chemical studies of the olfactory bulb have been performed in small rodents, such as rats and mice. Thus, this study aimed to describe the organisation and the chemical neuroanatomy of the main olfactory bulb (MOB) in paca, a large rodent belonging to the Hystricomorpha suborder and Caviomorpha infraorder. For this purpose, histological and immunohistochemical procedures were used to characterise the tyrosine hydroxylase (TH) and calretinin (CR) neuronal populations and their distribution. The paca MOB has eight layers: the olfactory nerve layer (ONL), the glomerular layer (GL), the external plexiform layer (EPL; subdivided into the inner and outer sublayers), the mitral cell layer (MCL), the internal plexiform layer (IPL), the granule cell layer (GCL), the periventricular layer and the ependymal layer. TH-ir neurons were found mostly in the GL, and moderate numbers of TH-ir neurons were scattered in the EPL. Numerous varicose fibres were distributed in the IPL and in the GCL. CR-ir neurons concentrated in the GL, around the base of the olfactory glomeruli. Most of the CR-ir neurons were located in the MCL, IPL and GCL. Some of the granule cells had an apical dendrite with a growth cone. The CR immunoreactivity was also observed in the ONL with olfactory nerves strongly immunostained. This study has shown that the MOB organisation in paca is consistent with the description in other mammals. The characterisation and distribution of the population of TH and CR in the MOB is not exclusively to this species. This large rodent shares common patterns to other caviomorph rodent, as guinea pig, and to the myomorph rodents, as mice, rats and hamsters.

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

PubMed Central

Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

2016-01-01

Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

Identification and embryonic expression of a new AP-2 transcription factor, AP-2 epsilon.

PubMed

Wang, Hao-Ven; Vaupel, Kristina; Buettner, Reinhard; Bosserhoff, Anja-Katrin; Moser, Markus

2004-09-01

AP-2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP-2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest-derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP-2 genes, we identified a fifth, previously unknown AP-2-related gene, AP-2 epsilon. AP-2 epsilon encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP-2 transcription factors with highly conserved C-terminal DNA binding and dimerization domains. Although the N-terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase-polymerase chain reaction analyses of murine embryos revealed AP-2 epsilon expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole-mount in situ hybridization using a specific AP-2 epsilon cDNA fragment demonstrated that during embryogenesis, expression of AP-2 epsilon is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP-2 epsilon-specific antiserum. By using this antiserum, we could further localize AP-2 epsilon expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP-2 epsilon for the development of the olfactory system.

Mice with a "monoclonal nose": perturbations in an olfactory map impair odor discrimination.

PubMed

Fleischmann, Alexander; Shykind, Benjamin M; Sosulski, Dara L; Franks, Kevin M; Glinka, Meredith E; Mei, Dan Feng; Sun, Yonghua; Kirkland, Jennifer; Mendelsohn, Monica; Albers, Mark W; Axel, Richard

2008-12-26

We have altered the neural representation of odors in the brain by generating a mouse with a "monoclonal nose" in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced 20-fold. We observe that these mice can smell, but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

Functional asymmetry of left and right avian piriform cortex in homing pigeons' navigation.

PubMed

Gagliardo, Anna; Odetti, Francesca; Ioalè, Paolo; Pecchia, Tommaso; Vallortigara, Giorgio

2005-07-01

It has been shown that homing pigeons rely on olfactory cues to navigate over unfamiliar areas and that any kind of olfactory impairment produces a dramatic reduction of navigational performance from unfamiliar sites. The avian piriform cortex is the main projection field of olfactory bulbs and it is supposed to process olfactory information; not surprisingly bilateral lesions to this telencephalic region disrupt homing pigeon navigation. In the present study, we attempted to assess whether the left and right piriform cortex are differentially involved in the use of the olfactory navigational map. Therefore, we released from unfamiliar locations pigeons subjected, when adult, to unilateral ablation of the piriform cortex. After being released, the pigeons lesioned to the right piriform cortex orientated similarly to the intact controls. On the contrary, the left lesioned birds were significantly more scattered than controls, showing a crucial role of the left piriform cortex in processing the olfactory cues needed for determining the direction of displacement. However, both lesioned groups were significantly slower than controls in flying back to the home loft, showing that the integrity of both sides of the piriform cortex is necessary to accomplish the whole homing process.

Detection of Volatile Indicators of Illicit Substances by the Olfactory Receptors of Drosophila melanogaster

PubMed Central

Marshall, Brenton; Warr, Coral G.

2010-01-01

Insects can detect a large range of odors with a numerically simple olfactory system that delivers high sensitivity and accurate discrimination. Therefore, insect olfactory receptors hold great promise as biosensors for detection of volatile organic chemicals in a range of applications. The array of olfactory receptor neurons of Drosophila melanogaster is rapidly becoming the best-characterized natural nose. We have investigated the suitability of Drosophila receptors as detectors for volatiles with applications in law enforcement, emergency response, and security. We first characterized responses of the majority of olfactory neuron types to a set of diagnostic odorants. Being thus able to correctly identify neurons, we then screened for responses from 38 different types of neurons to 35 agents. We identified 13 neuron types with responses to 13 agents. As individual Drosophila receptor genes have been mapped to neuron types, we can infer which genes confer responsiveness to the neurons. The responses were confirmed for one receptor by expressing it in a nonresponsive neuron. The fly olfactory system is mainly adapted to detect volatiles from fermenting fruits. However, our findings establish that volatiles associated with illicit substances, many of which are of nonnatural origin, are also detected by Drosophila receptors. PMID:20530374

Effect of Olfactory Stimulus on the Flight Course of a Honeybee, Apis mellifera, in a Wind Tunnel.

PubMed

Ikeno, Hidetoshi; Akamatsu, Tadaaki; Hasegawa, Yuji; Ai, Hiroyuki

2013-12-31

It is known that the honeybee, Apis mellifera, uses olfactory stimulus as important information for orienting to food sources. Several studies on olfactory-induced orientation flight have been conducted in wind tunnels and in the field. From these studies, optical sensing is used as the main information with the addition of olfactory signals and the navigational course followed by these sensory information. However, it is not clear how olfactory information is reflected in the navigation of flight. In this study, we analyzed the detailed properties of flight when oriented to an odor source in a wind tunnel. We recorded flying bees with a video camera to analyze the flight area, speed, angular velocity and trajectory. After bees were trained to be attracted to a feeder, the flight trajectories with or without the olfactory stimulus located upwind of the feeder were compared. The results showed that honeybees flew back and forth in the proximity of the odor source, and the search range corresponded approximately to the odor spread area. It was also shown that the angular velocity was different inside and outside the odor spread area, and trajectories tended to be bent or curved just outside the area.

Biomimetic chemical sensors using bioengineered olfactory and taste cells.

PubMed

Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping; Wu, Chunsheng

2014-01-01

Biological olfactory and taste systems are natural chemical sensing systems with unique performances for the detection of environmental chemical signals. With the advances in olfactory and taste transduction mechanisms, biomimetic chemical sensors have achieved significant progress due to their promising prospects and potential applications. Biomimetic chemical sensors exploit the unique capability of biological functional components for chemical sensing, which are often sourced from sensing units of biological olfactory or taste systems at the tissue level, cellular level, or molecular level. Specifically, at the cellular level, there are mainly two categories of cells have been employed for the development of biomimetic chemical sensors, which are natural cells and bioengineered cells, respectively. Natural cells are directly isolated from biological olfactory and taste systems, which are convenient to achieve. However, natural cells often suffer from the undefined sensing properties and limited amount of identical cells. On the other hand, bioengineered cells have shown decisive advantages to be applied in the development of biomimetic chemical sensors due to the powerful biotechnology for the reconstruction of the cell sensing properties. Here, we briefly summarized the most recent advances of biomimetic chemical sensors using bioengineered olfactory and taste cells. The development challenges and future trends are discussed as well.

Categorization of biologically relevant chemical signals in the medial amygdala

PubMed Central

Samuelsen, Chad L.; Meredith, Michael

2009-01-01

Many species employ chemical signals to convey messages between members of the same species (conspecific), but chemosignals may also provide information to another species (heterospecific). Here, we found that conspecific chemosignals (male, female mouse urine) increased immediate early gene-protein (IEG) expression in both anterior and posterior medial amygdala of male mice, whereas most heterospecific chemosignals (e.g.: hamster vaginal fluid, steer urine) increased expression only in anterior medial amygdala. This categorization of responses in medial amygdala conforms to our previously reported findings in male hamsters. The same characteristic pattern of IEG expression appears in the medial amygdala of each species in response to conspecific stimuli for that species. These results suggest that the amygdala categorizes stimuli according to the biological relevance for the tested species. Thus, a heterospecific predator (cat collar) stimulus, which elicited behavioral avoidance in mice, increased IEG expression in mouse posterior medial amygdala (like conspecific stimuli). Further analysis suggests reproduction related and potentially threatening stimuli produce increased IEG expression in different sub-regions of posterior medial amygdala (dorsal and ventral, respectively). These patterns of IEG expression in medial amygdala may provide glimpses of a tertiary sorting of chemosensory signals beyond the primary-level selectivity of chemosensory neurons and the secondary sorting in main and accessory olfactory bulbs. PMID:19368822

A competitive binding model predicts the response of mammalian olfactory receptors to mixtures

NASA Astrophysics Data System (ADS)

Singh, Vijay; Murphy, Nicolle; Mainland, Joel; Balasubramanian, Vijay

Most natural odors are complex mixtures of many odorants, but due to the large number of possible mixtures only a small fraction can be studied experimentally. To get a realistic understanding of the olfactory system we need methods to predict responses to complex mixtures from single odorant responses. Focusing on mammalian olfactory receptors (ORs in mouse and human), we propose a simple biophysical model for odor-receptor interactions where only one odor molecule can bind to a receptor at a time. The resulting competition for occupancy of the receptor accounts for the experimentally observed nonlinear mixture responses. We first fit a dose-response relationship to individual odor responses and then use those parameters in a competitive binding model to predict mixture responses. With no additional parameters, the model predicts responses of 15 (of 18 tested) receptors to within 10 - 30 % of the observed values, for mixtures with 2, 3 and 12 odorants chosen from a panel of 30. Extensions of our basic model with odorant interactions lead to additional nonlinearities observed in mixture response like suppression, cooperativity, and overshadowing. Our model provides a systematic framework for characterizing and parameterizing such mixing nonlinearities from mixture response data.

Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

PubMed Central

Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

2013-01-01

The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

Modulation of dendrodendritic interactions and mitral cell excitability in the mouse accessory olfactory bulb by vaginocervical stimulation.

PubMed

Otsuka, T; Ishii, K; Osako, Y; Okutani, F; Taniguchi, M; Oka, T; Kaba, H

2001-05-01

When female mice are mated, they form a memory to the pheromonal signal of their male partner. The neural changes underlying this memory occur in the accessory olfactory bulb, depend upon vaginocervical stimulation at mating and involve changes at the reciprocal synapses between mitral and granule cells. However, the action of vaginocervical stimulation on the reciprocal interactions between mitral and granule cells remains to be elucidated. We have examined the effects of vaginocervical stimulation on paired-pulse depression of amygdala-evoked field potentials recorded in the external plexiform layer of the accessory olfactory bulb (AOB) and the single-unit activity of mitral cells antidromically stimulated from the amygdala in urethane-anaesthetized female mice. Artificial vaginocervical stimulation reduced paired-pulse depression (considered to be due to feedback inhibition of the mitral cell dendrites from the granule cells via reciprocal dendrodendritic synapses) recorded in the AOB external plexiform layer. As would be expected from this result, vaginocervical stimulation also enhanced the spontaneous activity of a proportion of the mitral cells tested. These results suggest that vaginocervical stimulation reduces dendrodendritic feedback inhibition to mitral cells and enhances their activity.

Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus.

PubMed

Smalheiser, Neil R; Lugli, Giovanni; Lenon, Angela L; Davis, John M; Torvik, Vetle I; Larson, John

2010-02-26

Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of approximately 40 min of training). The hippocampus was dissected bilaterally from each mouse (N = 7 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIβ), CREB1 (cAMP-response-element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

ARX/Arx is expressed in germ cells during spermatogenesis in both marsupial and mouse.

PubMed

Yu, Hongshi; Pask, Andrew J; Hu, Yanqiu; Shaw, Geoff; Renfree, Marilyn B

2014-03-01

The X-linked aristaless gene, ARX, is essential for the development of the gonads, forebrain, olfactory bulb, pancreas, and skeletal muscle in mice and humans. Mutations cause neurological diseases, often accompanied by ambiguous genitalia. There are a disproportionately high number of testis and brain genes on the human and mouse X chromosomes. It is still unknown whether the X chromosome accrued these genes during its evolution or whether genes that find themselves on the X chromosome evolve such roles. ARX was originally autosomal in mammals and remains so in marsupials, whereas in eutherian mammals it translocated to the X chromosome. In this study, we examined autosomal ARX in tammars and compared it with the X-linked Arx in mice. We detected ARX mRNA in the neural cells of the forebrain, midbrain and hindbrain, and olfactory bulbs in developing tammars, consistent with the expression in mice. ARX was detected by RT-PCR and mRNA in situ hybridization in the developing tammar wallaby gonads of both sexes, suggestive of a role in sexual development as in mice. We also detected ARX/Arx mRNA in the adult testis in both tammars and mice, suggesting a potential novel role for ARX/Arx in spermiogenesis. ARX transcripts were predominantly observed in round spermatids. Arx mRNA localization distributions in the mouse adult testis suggest that it escaped meiotic sex chromosome inactivation during spermatogenesis. Our findings suggest that ARX in the therian mammal ancestor already played a role in male reproduction before it was recruited to the X chromosome in eutherians.

Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain.

PubMed

Rizzi, Sandra; Knaus, Hans-Günther; Schwarzer, Christoph

2016-07-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high-conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093-2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.

PubMed

Tong, Jia; Okutani, Fumino; Murata, Yoshihiro; Taniguchi, Mutsuo; Namba, Toshiharu; Wang, Yu-Jie; Kaba, Hideto

2017-03-06

Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

NMDA-receptor dependent synaptic activation of TRPC channels in olfactory bulb granule cells

PubMed Central

Stroh, Olga; Freichel, Marc; Kretz, Oliver; Birnbaumer, Lutz; Hartmann, Jana; Egger, Veronica

2012-01-01

TRPC channels are widely expressed throughout the nervous system including the olfactory bulb where their function is largely unknown. Here we describe their contribution to central synaptic processing at the reciprocal mitral and tufted cell - granule cell microcircuit, the most abundant synapse of the mammalian olfactory bulb. Suprathreshold activation of the synapse causes sodium action potentials in mouse granule cells and a subsequent long-lasting depolarization (LLD) linked to a global dendritic postsynaptic calcium signal recorded with two-photon laser scanning microscopy. These signals are not observed after action potentials evoked by current injection in the same cells. The LLD persists in the presence of group I metabotropic glutamate receptor antagonists but is entirely absent from granule cells deficient for the NMDA receptor subunit NR1. Moreover, both depolarization and Ca2+ rise are sensitive to the blockade of NMDA receptors. The LLD and the accompanying Ca2+ rise are also absent in granule cells from mice deficient for both TRPC channel subtypes 1 and 4, whereas the deletion of either TRPC1 or TRPC4 results in only a partial reduction of the LLD. Recordings from mitral cells in the absence of both subunits reveal a reduction of asynchronous neurotransmitter release from the granule cells during recurrent inhibition. We conclude that TRPC1 and TRPC4 can be activated downstream of NMDA receptor activation and contribute to slow synaptic transmission in the olfactory bulb, including the calcium dynamics required for asynchronous release from the granule cell spine. PMID:22539836

Olfactory ability and object memory in three mouse models of varying body weight, metabolic hormones, and adiposity

PubMed Central

Tucker, Kristal R.; Godbey, Steven J.; Thiebaud, Nicolas; Fadool, Debra Ann

2012-01-01

Physiological and nutritional state can modify sensory ability and perception through hormone signaling. Obesity and related metabolic disorders present a chronic imbalance in hormonal signaling that could impact sensory systems. In the olfactory system, external chemical cues are transduced into electrical signals to encode information. It is becoming evident that this system can also detect internal chemical cues in the form of molecules of energy homeostasis and endocrine hormones, whereby neurons of the olfactory system are modulated to change animal behavior towards olfactory cues. We hypothesized that chronic imbalance in hormonal signaling and energy homeostasis due to obesity would thereby disrupt olfactory behaviors in mice. To test this idea, we utilized three mouse models of varying body weight, metabolic hormones, and visceral adiposity – 1) C57BL6/J mice maintained on a condensed-milk based, moderately high-fat diet (MHF) of 32% fat for 6 months as the diet-induced obesity model, 2) an obesity-resistant, lean line of mice due to a gene-targeted deletion of a voltage-dependent potassium channel (Kv1.3-null), and 3) a genetic model of obesity as a result of a gene-targeted deletion of the melanocortin 4 receptor (MC4R-null). Diet-induced obese (DIO) mice failed to find fatty-scented hidden peanut butter cracker, based solely on olfactory cues, any faster than an unscented hidden marble, initially suggesting general anosmia. However, when these DIO mice were challenged to find a sweet-scented hidden chocolate candy, they had no difficulty. Furthermore, DIO mice were able to discriminate between fatty acids that differ by a single double bond and are components of the MHF diet (linoleic and oleic acid) in a habituation-dishabituation paradigm. Obesity-resistant, Kv1.3-null mice exhibited no change in scented object retrieval when placed on the MHF-diet, nor did they perform differently than wild-type mice in parallel habituation-dishabituation paradigms of fatty food-related odor components. Genetically obese, MC4R-null mice successfully found hidden scented objects, but did so more slowly than lean, wild-type mice, in an object-dependent fashion. In habituation-dishabituation trials of general odorants, MC4R-null mice failed to discriminate a novel odor, but were able to distinguish two fatty acids. Object memory recognition tests for short- and long-term memory retention demonstrated that maintenance on the MHF diet did not modify ability to perform these tasks independent of whether mice became obese or were resistant to weight gain (Kv1.3-null), however, the genetically predisposed obese mice (MC4R-null) failed the long-term object memory recognition performed at 24 hours. These results demonstrate that even though both the DIO mice and genetically predisposed obese mice are obese, they vary in the degree to which they exhibit behavioral deficits in odor detection, odor discrimination, and long-term memory. PMID:22995978

Direct neural pathways convey distinct visual information to Drosophila mushroom bodies

PubMed Central

Vogt, Katrin; Aso, Yoshinori; Hige, Toshihide; Knapek, Stephan; Ichinose, Toshiharu; Friedrich, Anja B; Turner, Glenn C; Rubin, Gerald M; Tanimoto, Hiromu

2016-01-01

Previously, we demonstrated that visual and olfactory associative memories of Drosophila share mushroom body (MB) circuits (Vogt et al., 2014). Unlike for odor representation, the MB circuit for visual information has not been characterized. Here, we show that a small subset of MB Kenyon cells (KCs) selectively responds to visual but not olfactory stimulation. The dendrites of these atypical KCs form a ventral accessory calyx (vAC), distinct from the main calyx that receives olfactory input. We identified two types of visual projection neurons (VPNs) directly connecting the optic lobes and the vAC. Strikingly, these VPNs are differentially required for visual memories of color and brightness. The segregation of visual and olfactory domains in the MB allows independent processing of distinct sensory memories and may be a conserved form of sensory representations among insects. DOI: http://dx.doi.org/10.7554/eLife.14009.001 PMID:27083044

Guidepost neurons for the lateral olfactory tract: expression of metabotropic glutamate receptor 1 and innervation by glutamatergic olfactory bulb axons.

PubMed

Hirata, Tatsumi; Kumada, Tatsuro; Kawasaki, Takahiko; Furukawa, Tomonori; Aiba, Atsu; Conquet, François; Saga, Yumiko; Fukuda, Atsuo

2012-12-01

The guidepost neurons for the lateral olfactory tract, which are called lot cells, are the earliest-generated neurons in the neocortex. They migrate tangentially and ventrally further down this tract, and provide scaffolding for the olfactory bulb axons projecting into this pathway. The molecular profiles of the lot cells are largely uncharacterized. We found that lot cells specifically express metabotropic glutamate receptor subtype-1 at a very early stage of development. This receptor is functionally competent and responds to a metabotropic glutamate receptor agonist with a transient increase in the intracellular calcium ion concentration. When the glutamatergic olfactory bulb axons were electrically stimulated, lot cells responded to the stimulation with a calcium increase mainly via ionotropic glutamate receptors, suggesting potential neurotransmission between the axons and lot cells during early development. Together with the finding that lot cells themselves are glutamatergic excitatory neurons, our results provide another notable example of precocious interactions between the projecting axons and their intermediate targets. Copyright © 2012 Wiley Periodicals, Inc.

Noradrenergic induction of odor-specific neural habituation and olfactory memories

PubMed Central

Shea, Stephen D.; Katz, Lawrence C.; Mooney, Richard

2008-01-01

For many mammals, individual recognition of conspecifics relies on olfactory cues. Certain individual recognition memories are thought to be stored when conspecific odor cues coincide with surges of noradrenaline (NA) triggered by intensely arousing social events. Such familiar stimuli elicit reduced behavioral responses, a change likely related to NA-dependent plasticity in the olfactory bulb (OB). In addition to its role in these ethological memories, NA signaling in the OB appears to be relevant for the discrimination of more arbitrary odorants as well. Nonetheless, no NA-gated mechanism of long-term plasticity in the OB has ever been directly observed in vivo. Here we report that NA release from locus coeruleus (LC), when coupled to odor presentation, acts locally in the main olfactory bulb (MOB) to cause a specific long-lasting suppression of respones to paired odors. These effects were observed for both food odors and urine, an important social recognition cue. Moreover, in subsequent behavioral tests, mice exhibited habituation to paired urine stimuli, suggesting that this LC-mediated olfactory neural plasticity, induced under anesthesia, can store an individual recognition memory that is observable upon recovery. PMID:18923046

An interglomerular circuit gates glomerular output and implements gain control in the mouse olfactory bulb

PubMed Central

Banerjee, Arkarup; Marbach, Fred; Anselmi, Francesca; Koh, Matthew S.; Davis, Martin B.; da Silva, Pedro Garcia; Delevich, Kristen; Oyibo, Hassana K.; Gupta, Priyanka; Li, Bo; Albeanu, Dinu F.

2015-01-01

Summary Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness. PMID:26139373

ϒ Spike-Field Coherence in a Population of Olfactory Bulb Neurons Differentiates between Odors Irrespective of Associated Outcome

PubMed Central

Li, Anan; Gire, David H.

2015-01-01

Studies in different sensory systems indicate that short spike patterns within a spike train that carry items of sensory information can be extracted from the overall train by using field potential oscillations as a reference (Kayser et al., 2012; Panzeri et al., 2014). Here we test the hypothesis that the local field potential (LFP) provides the temporal reference frame needed to differentiate between odors regardless of associated outcome. Experiments were performed in the olfactory system of the mouse (Mus musculus) where the mitral/tufted (M/T) cell spike rate develops differential responses to rewarded and unrewarded odors as the animal learns to associate one of the odors with a reward in a go–no go behavioral task. We found that coherence of spiking in M/T cells with the ϒ LFP (65 to 95 Hz) differentiates between odors regardless of the associated behavioral outcome of odor presentation. PMID:25855190

Modelling the emergence of rodent filial huddling from physiological huddling

NASA Astrophysics Data System (ADS)

Wilson, Stuart P.

2017-11-01

Huddling behaviour in neonatal rodents reduces the metabolic costs of physiological thermoregulation. However, animals continue to huddle into adulthood, at ambient temperatures where they are able to sustain a basal metabolism in isolation from the huddle. This `filial huddling' in older animals is known to be guided by olfactory rather than thermal cues. The present study aimed to test whether thermally rewarding contacts between young mice, experienced when thermogenesis in brown adipose fat tissue (BAT) is highest, could give rise to olfactory preferences that persist as filial huddling interactions in adults. To this end, a simple model was constructed to fit existing data on the development of mouse thermal physiology and behaviour. The form of the model that emerged yields a remarkable explanation for filial huddling; associative learning maintains huddling into adulthood via processes that reduce thermodynamic entropy from BAT metabolism and increase information about social ordering among littermates.

G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons

PubMed Central

Connelly, Timothy; Yu, Yiqun; Grosmaitre, Xavier; Wang, Jue; Santarelli, Lindsey C.; Savigner, Agnes; Qiao, Xin; Wang, Zhenshan; Storm, Daniel R.; Ma, Minghong

2015-01-01

Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR–G protein coupling eliminates mechanical responses. Curiously, OSNs expressing different OR types display significantly different responses to mechanical stimuli. Genetic swap of putatively mechanosensitive ORs abolishes or reduces mechanical responses of OSNs. Furthermore, ectopic expression of an OR restores mechanosensitivity in loss-of-function OSNs. Lastly, heterologous expression of an OR confers mechanosensitivity to its host cells. These results indicate that certain ORs are both necessary and sufficient to cause mechanical responses, revealing a previously unidentified mechanism for mechanotransduction. PMID:25550517

Chemosensory function of the amygdala.

PubMed

Gutiérrez-Castellanos, Nicolás; Martínez-Marcos, Alino; Martínez-García, Fernando; Lanuza, Enrique

2010-01-01

The chemosensory amygdala has been traditionally divided into two divisions based on inputs from the main (olfactory amygdala) or accessory (vomeronasal amygdala) olfactory bulbs, supposedly playing different and independent functional roles detecting odors and pheromones, respectively. Recently, there has been increased anatomical evidence of convergence inputs from the main and accessory bulbs in some areas of the amygdala, and this is correlated with functional evidence of interrelationships between the olfactory and the vomeronasal systems. This has lead to the characterization of a third division of the chemosensory amygdala, the mixed chemosensory amygdala, providing a new perspective of how chemosensory information is processed in the amygdaloid complex, in particular in relation to emotional behaviors. In this chapter, we analyze the anatomical and functional organization of the chemosensory amygdala from this new perspective. Finally, the evolutionary changes of the chemosensory nuclei of the mammalian amygdala are discussed, paying special attention to the case of primates, including humans. Copyright © 2010 Elsevier Inc. All rights reserved.

Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer's disease.

PubMed

Wang, Yue; Wu, Zheng; Bai, Yu-Ting; Wu, Gang-Yi; Chen, Gong

2017-10-10

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD pathology has not been well studied. Here, we investigate the functional role of GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by replacing one allele of Gad67 with green fluorescent protein (GFP) gene during generation of GAD67-GFP mice. To genetically reduce GAD67 in AD mouse brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP +/- ) with 5xFAD mice (harboring 5 human familial AD mutations in APP and PS1 genes) to generate a new line of bigenic mice. Immunostaining, ELISA, electrophysiology and behavior test were applied to compare the difference between groups. We found that reduction of GAD67 resulted in a significant decrease of amyloid β production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic GABA currents, as well as the microglial reactivity were significantly reduced in the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency. Our results demonstrate that GAD67 plays an important role in AD pathology, suggesting that GAD67 may be a potential drug target for modulating the progress of AD.

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

PubMed Central

Liu, Ying-Juan; Zhang, Yao-Hua; Li, Lai-Fu; Du, Rui-Qing; Zhang, Jin-Hua; Zhang, Jian-Xu

2016-01-01

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. PMID:26756471

Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

PubMed

Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

2010-11-01

When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

Study of smell and reproductive organs in a mouse model for CHARGE syndrome

PubMed Central

Bergman, Jorieke EH; Bosman, Erika A; van Ravenswaaij-Arts, Conny MA; Steel, Karen P

2010-01-01

CHARGE syndrome is a multiple congenital anomaly syndrome characterised by Coloboma, Heart defects, Atresia of choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear anomalies often associated with deafness. It is caused by heterozygous mutations in the CHD7 gene and shows a highly variable phenotype. Anosmia and hypogonadotropic hypogonadism occur in the majority of the CHARGE patients, but the underlying pathogenesis is unknown. Therefore, we studied the ability to smell and aspects of the reproductive system (reproductive performance, gonadotropin-releasing hormone (GnRH) neurons and anatomy of testes and uteri) in a mouse model for CHARGE syndrome, the whirligig mouse (Chd7Whi/+). We showed that Chromodomain Helicase DNA-binding protein 7 (Chd7) is expressed in brain areas involved in olfaction and reproduction during embryonic development. We observed poorer performance in the smell test in adult Chd7Whi/+ mice, secondary either to olfactory dysfunction or to balance disturbances. Olfactory bulb and reproductive organ abnormalities were observed in a proportion of Chd7Whi/+ mice. Hypothalamic GnRH neurons were slightly reduced in Chd7Whi/+ females and reproductive performance was slightly less in Chd7Whi/+ mice. This study shows that the penetrance of anosmia and hypogonadotropic hypogonadism is lower in Chd7Whi/+ mice than in CHARGE patients. Interestingly, many phenotypic features of the Chd7 mutation showed incomplete penetrance in our model mice, despite the use of inbred, genetically identical mice. This supports the theory that the extreme variability of the CHARGE phenotype in both humans and mice might be attributed to variations in the fetal microenvironment or to purely stochastic events. PMID:19809474

Interactions between behaviorally relevant rhythms and synaptic plasticity alter coding in the piriform cortex

PubMed Central

Urban, Nathaniel N.

2012-01-01

Understanding how neural and behavioral timescales interact to influence cortical activity and stimulus coding is an important issue in sensory neuroscience. In air-breathing animals, voluntary changes in respiratory frequency alter the temporal patterning olfactory input. In the olfactory bulb, these behavioral timescales are reflected in the temporal properties of mitral/tufted (M/T) cell spike trains. As the odor information contained in these spike trains is relayed from the bulb to the cortex, interactions between presynaptic spike timing and short-term synaptic plasticity dictate how stimulus features are represented in cortical spike trains. Here we demonstrate how the timescales associated with respiratory frequency, spike timing and short-term synaptic plasticity interact to shape cortical responses. Specifically, we quantified the timescales of short-term synaptic facilitation and depression at excitatory synapses between bulbar M/T cells and cortical neurons in slices of mouse olfactory cortex. We then used these results to generate simulated M/T population synaptic currents that were injected into real cortical neurons. M/T population inputs were modulated at frequencies consistent with passive respiration or active sniffing. We show how the differential recruitment of short-term plasticity at breathing versus sniffing frequencies alters cortical spike responses. For inputs at sniffing frequencies, cortical neurons linearly encoded increases in presynaptic firing rates with increased phase locked, firing rates. In contrast, at passive breathing frequencies, cortical responses saturated with changes in presynaptic rate. Our results suggest that changes in respiratory behavior can gate the transfer of stimulus information between the olfactory bulb and cortex. PMID:22553016

Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

PubMed Central

Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

2014-01-01

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011

Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Ensheathing Cells

PubMed Central

Tello Velasquez, Johana; Watts, Michelle E.; Todorovic, Michael; Nazareth, Lynnmaria; Pastrana, Erika; Diaz-Nido, Javier; Lim, Filip; Ekberg, Jenny A. K.; Quinn, Ronald J.; John, James A. St

2014-01-01

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies. PMID:25360677

Mouse Models of Autism: Testing Hypotheses About Molecular Mechanisms

PubMed Central

2012-01-01

Autism is a neurodevelopmental disorder that is currently diagnosed by the presence of three behavioral criteria (1) qualitative impairments in reciprocal social interactions, (2) deficits in communication, including delayed language and noninteractive conversation, and (3) motor stereotypies, repetitive behaviors, insistence on sameness, and restricted interests. This chapter describes analogous behavioral assays that have been developed for mice, including tests for social approach, reciprocal social interactions, olfactory communication, ultrasonic vocalizations, repetitive and perseverative behaviors, and motor stereotypies. Examples of assay applications to genetic mouse models of autism are provided. Robust endophenotypes that are highly relevant to the core symptoms of autism are enabling the search for the genetic and environmental causes of autism, and the discovery of effective treatments. PMID:21225409

Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons.

PubMed

Han, P; Lucero, M T

2005-01-01

Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death.

Functional imaging of cortical feedback projections to the olfactory bulb

PubMed Central

Rothermel, Markus; Wachowiak, Matt

2014-01-01

Processing of sensory information is substantially shaped by centrifugal, or feedback, projections from higher cortical areas, yet the functional properties of these projections are poorly characterized. Here, we used genetically-encoded calcium sensors (GCaMPs) to functionally image activation of centrifugal projections targeting the olfactory bulb (OB). The OB receives massive centrifugal input from cortical areas but there has been as yet no characterization of their activity in vivo. We focused on projections to the OB from the anterior olfactory nucleus (AON), a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons using a mouse line expressing Cre recombinase (Cre) in these neurons and Cre-dependent viral vectors injected into AON, allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Electrical stimulation of AON evoked large fluorescence signals that could be imaged from the dorsal OB surface in vivo. Surprisingly, odorants also evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP imaging revealed that different odorants activated different subsets of centrifugal AON axons and could elicit both excitation and suppression in different axons, indicating a surprising richness in the representation of odor information by cortical feedback to the OB. Finally, we found that activating neuromodulatory centers such as basal forebrain drove AON inputs to the OB independent of odorant stimulation. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory systems. PMID:25071454

Core Modular Blood and Brain Biomarkers in Social Defeat Mouse Model for Post Traumatic Stress Disorder

DTIC Science & Technology

2013-08-20

Affairs (VA) health care between 2002 and 2008 showed that 22% of veterans were diagnosed with PTSD and 17% were diagnosed with depression [1...30 Muscle contraction 12 Complement and Coagulation 31 Systemic lupus erythematosus 13 Olfactory transductoino 32 DNA Repair 14 Class A1 rhodopsin...Metzler TJ, Gima KS, Bertenthal D, Maguen S, Marmar CR: Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans using

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

Quantitative comparative analysis of the nasal chemosensory organs of anurans during larval development and metamorphosis highlights the relative importance of chemosensory subsystems in the group.

PubMed

Jungblut, Lucas David; Reiss, John O; Paz, Dante A; Pozzi, Andrea G

2017-09-01

The anuran peripheral olfactory system is composed of a number of subsystems, represented by distinct neuroepithelia. These include the main olfactory epithelium and vomeronasal organ (found in most tetrapods) and three specialized epithelia of anurans: the buccal-exposed olfactory epithelium of larvae, and the olfactory recess and middle chamber epithelium of postmetamorphic animals. To better characterize the developmental changes in these subsystems across the life cycle, morphometric changes of the nasal chemosensory organs during larval development and metamorphosis were analyzed in three different anuran species (Rhinella arenarum, Hypsiboas pulchellus, and Xenopus laevis). We calculated the volume of the nasal chemosensory organs by measuring the neuroepithelial area from serial histological sections at four different stages. In larvae, the vomeronasal organ was relatively reduced in R. arenarum compared with the other two species; the buccal-exposed olfactory epithelium was absent in X. laevis, and best developed in H. pulchellus. In postmetamorphic animals, the olfactory epithelium (air-sensitive organ) was relatively bigger in terrestrial species (R. arenarum and H. pulchellus), whereas the vomeronasal and the middle chamber epithelia (water-sensitive organs) was best developed in X. laevis. A small olfactory recess (likely homologous with the middle chamber epithelium) was found in R. arenarum juveniles, but not in H. pulchellus. These results support the association of the vomeronasal and middle chamber epithelia with aquatic olfaction, as seen by their enhanced development in the secondarily aquatic juveniles of X. laevis. They also support a role for the larval buccal-exposed olfactory epithelium in assessment of oral contents: it was absent in X. laevis, an obligate suspension feeder, while present in the two grazing species. These initial quantitative results give, for the first time, insight into the functional importance of the peripheral olfactory subsystems across the anuran life cycle. © 2017 Wiley Periodicals, Inc.

Peripheral and Central Olfactory Tuning in a Moth

PubMed Central

Ong, Rose C.

2012-01-01

Animals can be innately attracted to certain odorants. Because these attractants are particularly salient, they might be expected to induce relatively strong responses throughout the olfactory pathway, helping animals detect the most relevant odors but limiting flexibility to respond to other odors. Alternatively, specific neural wiring might link innately preferred odors to appropriate behaviors without a need for intensity biases. How nonpheromonal attractants are processed by the general olfactory system remains largely unknown. In the moth Manduca sexta, we studied this with a set of innately preferred host plant odors and other, neutral odors. Electroantennogram recordings showed that, as a population, olfactory receptor neurons (ORNs) did not respond with greater intensity to host plant odors, and further local field potential recordings showed that no specific amplification of signals induced by host plant odors occurred between the first olfactory center and the second. Moreover, when odorants were mutually diluted to elicit equally intense output from the ORNs, moths were able to learn to associate all tested odorants equally well with food reward. Together, these results suggest that, although nonpheromonal host plant odors activate broadly distributed responses, they may be linked to attractive behaviors mainly through specific wiring in the brain. PMID:22362866

Antennal transcriptome analysis of the Asian longhorned beetle Anoplophora glabripennis

PubMed Central

Hu, Ping; Wang, Jingzhen; Cui, Mingming; Tao, Jing; Luo, Youqing

2016-01-01

Olfactory proteins form the basis of insect olfactory recognition, which is crucial for host identification, mating, and oviposition. Using transcriptome analysis of Anoplophora glabripennis antenna, we identified 42 odorant-binding proteins (OBPs), 12 chemosensory proteins (CSPs), 14 pheromone-degrading enzymes (PDEs), 1 odorant-degrading enzymes (ODE), 37 odorant receptors (ORs), 11 gustatory receptors (GRs), 2 sensory neuron membrane proteins (SNMPs), and 4 ionotropic receptor (IR). All CSPs and PBPs were expressed in antennae, confirming the authenticity of the transcriptome data. CSP expression profiles showed that AglaCSP3, AglaCSP6, and AglaCSP12 were expressed preferentially in maxillary palps and AglaCSP7 and AglaCSP9 were strongly expressed in antennae. The vast majority of CSPs were highly expressed in multiple chemosensory tissues, suggesting their participation in olfactory recognition in almost all olfactory tissues. Intriguingly, the PBP AglaPBP2 was preferentially expressed in antenna, indicating that it is the main protein involved in efficient and sensitive pheromone recognition. Phylogenetic analysis of olfactory proteins indicated AglaGR1 may detect CO2. This study establishes a foundation for determining the chemoreception molecular mechanisms of A. glabripennis, which would provide a new perspective for controlling pest populations, especially those of borers. PMID:27222053

Introducing Computational Fluid Dynamics Simulation into Olfactory Display

NASA Astrophysics Data System (ADS)

Ishida, Hiroshi; Yoshida, Hitoshi; Nakamoto, Takamichi

An olfactory display is a device that delivers various odors to the user's nose. It can be used to add special effects to movies and games by releasing odors relevant to the scenes shown on the screen. In order to provide high-presence olfactory stimuli to the users, the display must be able to generate realistic odors with appropriate concentrations in a timely manner together with visual and audio playbacks. In this paper, we propose to use computational fluid dynamics (CFD) simulations in conjunction with the olfactory display. Odor molecules released from their source are transported mainly by turbulent flow, and their behavior can be extremely complicated even in a simple indoor environment. In the proposed system, a CFD solver is employed to calculate the airflow field and the odor dispersal in the given environment. An odor blender is used to generate the odor with the concentration determined based on the calculated odor distribution. Experimental results on presenting odor stimuli synchronously with movie clips show the effectiveness of the proposed system.

Functional MRI of the Olfactory System in Conscious Dogs

PubMed Central

Jia, Hao; Pustovyy, Oleg M.; Waggoner, Paul; Beyers, Ronald J.; Schumacher, John; Wildey, Chester; Barrett, Jay; Morrison, Edward; Salibi, Nouha; Denney, Thomas S.; Vodyanoy, Vitaly J.; Deshpande, Gopikrishna

2014-01-01

We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology. PMID:24466054

Vomeronasal and Olfactory Structures in Bats Revealed by DiceCT Clarify Genetic Evidence of Function

PubMed Central

Yohe, Laurel R.; Hoffmann, Simone; Curtis, Abigail

2018-01-01

The degree to which molecular and morphological loss of function occurs synchronously during the vestigialization of traits is not well understood. The mammalian vomeronasal system, a sense critical for mediating many social and reproductive behaviors, is highly conserved across mammals. New World Leaf-nosed bats (Phyllostomidae) are under strong selection to maintain a functional vomeronasal system such that most phyllostomids possess a distinct vomeronasal organ and an intact TRPC2, a gene encoding a protein primarily involved in vomeronasal sensory neuron signal transduction. Recent genetic evidence, however, shows that TRPC2 is a pseudogene in some Caribbean nectarivorous phyllostomids. The loss-of-function mutations suggest the sensory neural tissue of the vomeronasal organ is absent in these species despite strong selection on this gene in its mainland relatives, but the anatomy was unknown in most Caribbean nectarivorous phyllostomids until this study. We used diffusible iodine-based contrast-enhanced computed tomography (diceCT) to test whether the vomeronasal and main olfactory anatomy of several phyllostomid species matched genetic evidence of function, providing insight into whether loss of a structure is linked to pseudogenization of a molecular component of the system. The vomeronasal organ is indeed rudimentary or absent in species with a disrupted TRPC2 gene. Caribbean nectar-feeders also exhibit derived olfactory turbinal morphology and a large olfactory recess that differs from closely related bats that have an intact vomeronasal organ, which may hint that the main olfactory system may compensate for loss. We emphasize non-invasive diceCT is capable of detecting the vomeronasal organ, providing a feasible approach for quantifying mammalian chemosensory anatomy across species. PMID:29867373

Characterization of a new Gsx2-cre line in the developing mouse telencephalon.

PubMed

Qin, Shenyue; Madhavan, Mayur; Waclaw, Ronald R; Nakafuku, Masato; Campbell, Kenneth

2016-10-01

In this study, we generated a transgenic mouse line driving Cre and EGFP expression with two putative cis-regulatory modules (CRMs) (i.e., hs687 and hs678) upstream of the homeobox gene Gsx2 (formerly Gsh2), a critical gene for establishing lateral ganglionic eminence (LGE) identity. The combination of these two CRMs drives transgene expression within the endogenous Gsx2 expression domains along the anterior-posterior neuraxis. By crossing this transgenic line with the Rosa tdTomato (Ai14) reporter mouse line, we observed a unique recombination pattern in the lateral ventral telencephalon, namely the LGE and the dorsal half of the medial GE (MGE), but not in the septum. We found robust recombination in many cell types derived from these embryonic regions, including olfactory bulb and amygdala interneurons and striatal projection neurons from the LGE, as well as cortical interneurons from the MGE and caudal GE (CGE). In summary, this transgenic mouse line represents a new tool for genetic manipulation in the LGE/CGE and the dorsal half of MGE. © 2016 Wiley Periodicals, Inc.

The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.

PubMed

Xu, Lili; Bao, Linlin; Deng, Wei; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Yong, Weidong; Wei, Qiang; Zhang, Lianfeng; Qin, Chuan

2013-08-08

The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus. A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3-5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models. The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

Primary cell culture of LHRH neurones from embryonic olfactory placode in the sheep (Ovis aries).

PubMed

Duittoz, A H; Batailler, M; Caldani, M

1997-09-01

The aim of this study was to establish an in vitro model of ovine luteinizing hormone-releasing hormone (LHRH) neurones. Olfactory placodes from 26 day-old sheep embryos (E26) were used for explant culture. Cultures were maintained successfully up to 35 days, but were usually used at 17 days for immunocytochemistry. LHRH and neuronal markers such as neurofilament (NF) were detected by immunocytochemistry within and/or outside the explant. Three main types of LHRH positive cells are described: (1) neuroblastic LHRH and NF immunoreactive cells with round cell body and very short neurites found mainly within the explant, (2) migrating LHRH bipolar neurones with an fusiform cell body, found outside the explant, (3) network LHRH neuron, bipolar or multipolar with long neurites connecting other LHRH neurons. Cell morphology was very similar to that which has been described in the adult sheep brain. These results strongly suggest that LHRH neurones in the sheep originate from the olfactory placode. This mode may represent a useful tool to study LHRH neurones directly in the sheep.

Mutual influences between the main olfactory and vomeronasal systems in development and evolution

PubMed Central

Suárez, Rodrigo; García-González, Diego; de Castro, Fernando

2012-01-01

The sense of smell plays a crucial role in the sensory world of animals. Two chemosensory systems have been traditionally thought to play-independent roles in mammalian olfaction. According to this, the main olfactory system (MOS) specializes in the detection of environmental odorants, while the vomeronasal system (VNS) senses pheromones and semiochemicals produced by individuals of the same or different species. Although both systems differ in their anatomy and function, recent evidence suggests they act synergistically in the perception of scents. These interactions include similar responses to some ligands, overlap of telencephalic connections and mutual influences in the regulation of olfactory-guided behavior. In the present work, we propose the idea that the relationships between systems observed at the organismic level result from a constant interaction during development and reflects a common history of ecological adaptations in evolution. We review the literature to illustrate examples of developmental and evolutionary processes that evidence these interactions and propose that future research integrating both systems may shed new light on the mechanisms of olfaction. PMID:23269914

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

PubMed

Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Identification of novel putative-binding proteins for cellular prion protein and a specific interaction with the STIP1 homology and U-Box-containing protein 1

PubMed Central

Gimenez, Ana Paula Lappas; Richter, Larissa Morato Luciani; Atherino, Mariana Campos; Beirão, Breno Castello Branco; Fávaro, Celso; Costa, Michele Dietrich Moura; Zanata, Silvio Marques; Malnic, Bettina; Mercadante, Adriana Frohlich

2015-01-01

ABSTRACT Prion diseases involve the conversion of the endogenous cellular prion protein, PrPC, into a misfolded infectious isoform, PrPSc. Several functions have been attributed to PrPC, and its role has also been investigated in the olfactory system. PrPC is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp−/− mice showed impaired behavior in olfactory tests. Given the high PrPC expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrPC-binding partners. Ten different putative PrPC ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrPC with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrPC-Stub1 interaction are under investigation. The PrPC-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrPC is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein. PMID:26237451

Muscarinic Receptors Modulate Dendrodendritic Inhibitory Synapses to Sculpt Glomerular Output

PubMed Central

Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus

2015-01-01

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. PMID:25855181

Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

PubMed

Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

2015-04-08

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain.

PubMed

Nakamura, Kouichi; Hioki, Hiroyuki; Fujiyama, Fumino; Kaneko, Takeshi

2005-11-21

Vesicular glutamate transporter 1 (VGluT1) and VGluT2 accumulate neurotransmitter glutamate into synaptic vesicles at presynaptic terminals, and their antibodies are thus considered to be a good marker for glutamatergic axon terminals. In the present study, we investigated the postnatal development and maturation of glutamatergic neuronal systems by single- and double-immunolabelings for VGluT1 and VGluT2 in mouse forebrain including the telencephalon and diencephalon. VGluT2 immunoreactivity was widely distributed in the forebrain, particularly in the diencephalon, from postnatal day 0 (P0) to adulthood, suggesting relatively early maturation of VGluT2-loaded glutamatergic axons. In contrast, VGluT1 immunoreactivity was intense only in the limbic regions at P0, and drastically increased in the other telencephalic and diencephalic regions during three postnatal weeks. Interestingly, VGluT1 immunoreactivity was frequently colocalized with VGluT2 immunoreactivity at single axon terminal-like profiles in layer IV of the primary somatosensory area from P5 to P10 and in the ventral posteromedial thalamic nucleus from P0 to P14. This was in sharp contrast to the finding that almost no colocalization was found in glomeruli of the olfactory bulb, patchy regions of the caudate-putamen, and the ventral posterolateral thalamic nucleus, where moderate to intense immunoreactivities for VGluT1 and VGluT2 were intermingled with each other in neuropil during postnatal development. The present results indicate that VGluT2-loaded glutamatergic axons maturate earlier than VGluT1-laden axons in the mouse telencephalic and diencephalic regions, and suggest that VGluT1 plays a transient developmental role in some glutamatergic systems that mainly use VGluT2 in the adulthood. (c) 2005 Wiley-Liss, Inc.

Miniaturized fiber-coupled confocal fluorescence microscope with an electrowetting variable focus lens using no moving parts

PubMed Central

Ozbay, Baris N.; Losacco, Justin T.; Cormack, Robert; Weir, Richard; Bright, Victor M.; Gopinath, Juliet T.; Restrepo, Diego; Gibson, Emily A.

2015-01-01

We report a miniature, lightweight fiber-coupled confocal fluorescence microscope that incorporates an electrowetting variable focus lens to provide axial scanning for full three-dimensional (3D) imaging. Lateral scanning is accomplished by coupling our device to a laser-scanning confocal microscope through a coherent imaging fiber-bundle. The optical components of the device are combined in a custom 3D-printed adapter with an assembled weight of <2 g that can be mounted onto the head of a mouse. Confocal sectioning provides an axial resolution of ~12 µm and an axial scan range of ~80 µm. The lateral field-of-view is 300 µm, and the lateral resolution is 1.8 µm. We determined these parameters by imaging fixed sections of mouse neuronal tissue labeled with green fluorescent protein (GFP) and fluorescent bead samples in agarose gel. To demonstrate viability for imaging intact tissue, we resolved multiple optical sections of ex vivo mouse olfactory nerve fibers expressing yellow fluorescent protein (YFP). PMID:26030555

Fos Expression in the Olfactory Pathway of High- and Low-Sexually Performing Rams Exposed to Urine from Estrous or Ovariectomized Ewes

PubMed Central

Mirto, AJ; Austin, KJ; Uthlaut, VA; Roselli, CE; Alexander, BM

2015-01-01

Exposure to estrous ewe urine stimulates investigation and mounting activity in sexually active but not sexually inactive rams. It was hypothesized sexual indifference may result from an inability to detect olfactory cues or an interruption of the pathway from detection of the olfactory stimulus to the motor response. Sexually active (n=4) and inactive (n=3) rams were exposed to urine from estrous ewes. An additional group of sexually active rams (n=3) were exposed to urine from ovariectomized ewes. Rams were exsanguinated following 1 h of exposure to stimulus. Neural activity was determined in tissues of interest by the presence of fos and fos-related proteins detected by immunohistochemistry procedures. Sexually active rams exposed to urine from ovariectomized ewes had more (P ≤ 0.05) fos-positive cells in the olfactory bulb, but fewer (P = 0.03) fos-positive cells in the cortical amygdala compared to sexually active rams exposed to urine from estrous ewes. Sexually inactive rams had similar (P ≥ 0.13) numbers of fos positive neurons in the olfactory bulb and medial amygdala but fewer (P ≤ 0.04) in the central amygdala, bed nucleus of the stria terminalis and the medial preoptic area compared to sexually active rams exposed to urine from estrous ewes. Sexual inactivity was not associated with decreased hypothalamic function since fos activity was similar (P ≥ 0.14) among groups in the suprachiasmatic and ventral medial nucleus. Sexual inactivity is not likely due to an impaired ability to detect or process olfactory stimuli by the main olfactory bulb and medial-cortical amygdala. Sexually inactive rams may have reduced attentiveness to sexual stimuli and/or decreased responsiveness of regions in the brain which regulate reproductive behaviors. PMID:28348447

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

PubMed Central

Ye, Qi; Kim, Jonghan

2015-01-01

Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe−/− mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe−/− mice. Compared with manganese-instilled wild-type mice, Hfe−/− mice showed decreased manganese accumulation in the cerebellum. Hfe−/− mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation. PMID:26189056

A Molecular Code for Identity in the Vomeronasal System.

PubMed

Fu, Xiaoyan; Yan, Yuetian; Xu, Pei S; Geerlof-Vidavsky, Ilan; Chong, Wongi; Gross, Michael L; Holy, Timothy E

2015-10-08

In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that "explain" patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse

PubMed Central

Dhawale, Ashesh K.; Hagiwara, Akari; Bhalla, Upinder S.; Murthy, Venkatesh N.; Albeanu, Dinu F.

2011-01-01

Sensory inputs frequently converge on the brain in a spatially organized manner, often with overlapping inputs to multiple target neurons. Whether the responses of target neurons with common inputs become decorrelated depends on the contribution of local circuit interactions. We addressed this issue in the olfactory system using newly generated transgenic mice expressing channelrhodopsin-2 in all olfactory sensory neurons. By selectively stimulating individual glomeruli with light, we identified mitral/tufted (M/T) cells that receive common input (sister cells). Sister M/T cells had highly correlated responses to odors as measured by average spike rates, but their spike timing in relation to respiration was differentially altered. In contrast, non-sister M/T cells correlated poorly on both these measures. We suggest that sister M/T cells carry two different channels of information: average activity representing shared glomerular input, and phase-specific information that refines odor representations and is substantially independent for sister M/T cells. PMID:20953197

Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4.

PubMed

Olofsson, Jonas K; Josefsson, Maria; Ekström, Ingrid; Wilson, Donald; Nyberg, Lars; Nordin, Steven; Nordin Adolfsson, Annelie; Adolfsson, Rolf; Nilsson, Lars-Göran; Larsson, Maria

2016-05-01

The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator. Copyright © 2016. Published by Elsevier Ltd.

Both odor identification and ApoE-ε4 contribute to normative cognitive aging.

PubMed

Finkel, Deborah; Reynolds, Chandra A; Larsson, Maria; Gatz, Margaret; Pedersen, Nancy L

2011-12-01

Research indicates that apoliprotein E (ApoE) plays a role in the development of Alzheimer's disease (AD) and possibly in the cognitive decline associated with normative aging. More recently, researchers have shown that ApoE is expressed in olfactory brain structures, and a relationship among ApoE, AD, and olfactory function has been proposed. In the current analyses, we investigated the contribution of ApoE and odor identification in decline trajectories associated with normative cognitive aging in various domains, using longitudinal data on cognitive performance available from the Swedish Adoption/Twin Study of Aging. Data on both ApoE status and olfactory functioning were available from 455 individuals ranging in age from 50 to 88 years at the first measurement occasion. Odor identification was measured via a mailed survey. Cognitive performance was assessed in up to 5 waves of in-person testing covering a period of 16 years. Latent growth curve analyses incorporating odor identification and ApoE status indicated a main effect of odor identification on the performance level in three cognitive domains: verbal, memory, and speed. A main effect of ApoE on rates of decline after age 65 was found for verbal, spatial, and speed factors. The consistency of results across cognitive domains provides support for theories that posit central nervous system-wide origins of the olfaction-cognition-ApoE relationship; however, olfactory errors and APOE ε4 show unique and differential effects on cognitive trajectory features.

Heterogeneous distribution of G protein alpha subunits in the main olfactory and vomeronasal systems of Rhinella (Bufo) arenarum tadpoles.

PubMed

Jungblut, Lucas D; Paz, Dante A; López-Costa, Juan J; Pozzi, Andrea G

2009-10-01

We evaluated the presence of G protein subtypes Galpha(o), Galpha(i2), and Galpha(olf) in the main olfactory system (MOS) and accessory or vomeronasal system (VNS) of Rhinella (Bufo) arenarum tadpoles, and here describe the fine structure of the sensory cells in the olfactory epithelium (OE) and vomeronasal organ (VNO). The OE shows olfactory receptor neurons (ORNs) with cilia in the apical surface, and the vomeronasal receptor neurons (VRNs) of the VNO are covered with microvilli. Immunohistochemistry detected the presence of at least two segregated populations of ORNs throughout the OE, coupled to Galpha(olf) and Galpha(o). An antiserum against Galpha(i2) was ineffective in staining the ORNs. In the VNO, Galpha(o) neurons stained strongly but lacked immunoreactivity to any other Galpha subunit in all larval stages analyzed. Western blot analyses and preabsorption experiments confirmed the specificity of the commercial antisera used. The functional significance of the heterogeneous G-protein distribution in R. arenarum tadpoles is not clear, but the study of G- protein distributions in various amphibian species is important, since this vertebrate group played a key role in the evolution of tetrapods. A more complete knowledge of the amphibian MOS and VNS would help to understand the functional organization and evolution of vertebrate chemosensory systems. This work demonstrates, for the first time, the existence of a segregated distribution of G-proteins in the OE of R. arenarum tadpoles.

External tufted cells in the main olfactory bulb form two distinct subpopulations.

PubMed

Antal, Miklós; Eyre, Mark; Finklea, Bryson; Nusser, Zoltan

2006-08-01

The glomeruli of the main olfactory bulb are the first processing station of the olfactory pathway, where complex interactions occur between sensory axons, mitral cells and a variety of juxtaglomerular neurons, including external tufted cells (ETCs). Despite a number of studies characterizing ETCs, little is known about how their morphological and functional properties correspond to each other. Here we determined the active and passive electrical properties of ETCs using in vitro whole-cell recordings, and correlated them with their dendritic arborization patterns. Principal component followed by cluster analysis revealed two distinct subpopulations of ETCs based on their electrophysiological properties. Eight out of 12 measured physiological parameters exhibited significant difference between the two subpopulations, including the membrane time constant, amplitude of spike afterhyperpolarization, variance in the interspike interval distribution and subthreshold resonance. Cluster analysis of the morphological properties of the cells also revealed two subpopulations, the most prominent dissimilarity between the groups being the presence or absence of secondary, basal dendrites. Finally, clustering the cells taking all measured properties into account also indicated the presence of two subpopulations that mapped in an almost perfect one-to-one fashion to both the physiologically and the morphologically derived groups. Our results demonstrate that a number of functional and structural properties of ETCs are highly predictive of one another. However, cells within each subpopulation exhibit pronounced variability, suggesting a large degree of specialization evolved to fulfil specific functional requirements in olfactory information processing.

External tufted cells in the main olfactory bulb form two distinct subpopulations

PubMed Central

Antal, Miklós; Eyre, Mark; Finklea, Bryson; Nusser, Zoltan

2006-01-01

The glomeruli of the main olfactory bulb are the first processing station of the olfactory pathway, where complex interactions occur between sensory axons, mitral cells and a variety of juxtaglomerular neurons, including external tufted cells (ETCs). Despite a number of studies characterizing ETCs, little is known about how their morphological and functional properties correspond to each other. Here we determined the active and passive electrical properties of ETCs using in vitro whole-cell recordings, and correlated them with their dendritic arborization patterns. Principal component followed by cluster analysis revealed two distinct subpopulations of ETCs based on their electrophysiological properties. Eight out of 12 measured physiological parameters exhibited significant difference between the two subpopulations, including the membrane time constant, amplitude of spike afterhyperpolarization, variance in the interspike interval distribution and subthreshold resonance. Cluster analysis of the morphological properties of the cells also revealed two subpopulations, the most prominent dissimilarity between the groups being the presence or absence of secondary, basal dendrites. Finally, clustering the cells taking all measured properties into account also indicated the presence of two subpopulations that mapped in an almost perfect one-to-one fashion to both the physiologically and the morphologically derived groups. Our results demonstrate that a number of functional and structural properties of ETCs are highly predictive of one another. However, cells within each subpopulation exhibit pronounced variability, suggesting a large degree of specialization evolved to fulfil specific functional requirements in olfactory information processing. PMID:16930438

Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells.

PubMed

Liu, Shaolin; Plachez, Celine; Shao, Zuoyi; Puche, Adam; Shipley, Michael T

2013-02-13

Evidence for coexpression of two or more classic neurotransmitters in neurons has increased, but less is known about cotransmission. Ventral tegmental area (VTA) neurons corelease dopamine (DA), the excitatory transmitter glutamate, and the inhibitory transmitter GABA onto target cells in the striatum. Olfactory bulb (OB) short axon cells (SACs) form interglomerular connections and coexpress markers for DA and GABA. Using an optogenetic approach, we provide evidence that mouse OB SACs release both GABA and DA onto external tufted cells (ETCs) in other glomeruli. Optical activation of channelrhodopsin specifically expressed in DAergic SACs produced a GABA(A) receptor-mediated monosynaptic inhibitory response, followed by DA-D(1)-like receptor-mediated excitatory response in ETCs. The GABA(A) receptor-mediated hyperpolarization activates I(h) current in ETCs; synaptically released DA increases I(h), which enhances postinhibitory rebound spiking. Thus, the opposing actions of synaptically released GABA and DA are functionally integrated by I(h) to generate an inhibition-to-excitation "switch" in ETCs. Consistent with the established role of I(h) in ETC burst firing, we show that endogenous DA release increases ETC spontaneous bursting frequency. ETCs transmit sensory signals to mitral/tufted output neurons and drive intraglomerular inhibition to shape glomerulus output to downstream olfactory networks. GABA and DA cotransmission from SACs to ETCs may play a key role in regulating output coding across the glomerular array.

Spontaneous calcium transients in the immature adult-born neurons of the olfactory bulb.

PubMed

Maslyukov, Anatoliy; Li, Kaizhen; Su, Xin; Kovalchuk, Yury; Garaschuk, Olga

2018-06-06

Spontaneous neuronal activity and concomitant intracellular Ca 2+ signaling are abundant during early perinatal development and are well known for their key role in neuronal proliferation, migration, differentiation and wiring. However, much less is known about the in vivo patterns of spontaneous Ca 2+ signaling in immature adult-born cells. Here, by using two-photon Ca 2+ imaging, we analyzed spontaneous in vivo Ca 2+ signaling in adult-born juxtaglomerular cells of the mouse olfactory bulb over the time period of 5 weeks, from the day of their arrival in the glomerular layer till their stable integration into the preexisting neural network. We show that spontaneous Ca 2+ transients are ubiquitously present in adult-born cells right after their arrival, require activation of voltage-gated Na + channels and are little sensitive to isoflurane anesthesia. Interestingly, several parameters of this spontaneous activity, such as the area under the curve, the time spent in the active state as well as the fraction of continuously active cells show a bell-shaped dependence on cell's age, all peaking in 3-4 weeks old cells. This data firmly document the in vivo presence of spontaneous Ca 2+ signaling during the layer-specific maturation of adult-born neurons in the olfactory bulb and motivate further analyses of the functional role(s) of this activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ancient genomic architecture for mammalian olfactory receptor clusters

PubMed Central

Aloni, Ronny; Olender, Tsviya; Lancet, Doron

2006-01-01

Background Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome. Results We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection. Conclusion The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence. PMID:17010214

Medullary neurons in the core white matter of the olfactory bulb: a new cell type.

PubMed

Paredes, Raúl G; Larriva-Sahd, Jorge

2010-02-01

The structure of a new cell type, termed the medullary neuron (MN) because of its intimate association with the rostral migratory stream (RMS) in the bulbar core, is described in the adult rat olfactory bulb. The MN is a triangular or polygonal interneuron whose soma lies between the cellular clusters of the RMS or, less frequently, among the neuron progenitors therein. MNs are easily distinguished from adjacent cells by their large size and differentiated structure. Two MN subtypes have been categorized by the Golgi technique: spiny pyramidal neurons and aspiny neurons. Both MN subtypes bear a large dendritic field impinged upon by axons in the core bulbar white matter. A set of collaterals from the adjacent axons appears to terminate on the MN dendrites. The MN axon passes in close apposition to adjacent neuron progenitors in the RMS. MNs are immunoreactive with antisera raised against gamma-aminobutyric acid and glutamate decarboxylase 65/67. Electron-microscopic observations confirm that MNs correspond to fully differentiated, mature neurons. MNs seem to be highly conserved among macrosmatic species as they occur in Nissl-stained brain sections from mouse, guinea pig, and hedgehog. Although the functional role of MNs remains to be determined, we suggest that MNs represent a cellular interface between endogenous olfactory activity and the differentiation of new neurons generated during adulthood.

Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments

PubMed Central

Coronas-Samano, Guillermo; Baker, Keeley L.; Tan, Winston J. T.; Ivanova, Alla V.; Verhagen, Justus V.

2016-01-01

Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4–5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral deficits of the Fus1 KO mice at this relatively young age are highly relevant to sAD, making them suitable for effective research on pharmacological targets in the context of early intervention of sAD. PMID:27895577

Brain region-dependent differential expression of alpha-synuclein.

PubMed

Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tsujimura, Atsushi; Tanaka, Masaki

2016-04-15

α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions. © 2015 Wiley Periodicals, Inc.

Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates

PubMed Central

Niimura, Yoshihito

2007-01-01

The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human–mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors. PMID:16607462

Temporal Response Properties of Accessory Olfactory Bulb Neurons: Limitations and Opportunities for Decoding.

PubMed

Yoles-Frenkel, Michal; Kahan, Anat; Ben-Shaul, Yoram

2018-05-23

The vomeronasal system (VNS) is a major vertebrate chemosensory system that functions in parallel to the main olfactory system (MOS). Despite many similarities, the two systems dramatically differ in the temporal domain. While MOS responses are governed by breathing and follow a subsecond temporal scale, VNS responses are uncoupled from breathing and evolve over seconds. This suggests that the contribution of response dynamics to stimulus information will differ between these systems. While temporal dynamics in the MOS are widely investigated, similar analyses in the accessory olfactory bulb (AOB) are lacking. Here, we have addressed this issue using controlled stimulus delivery to the vomeronasal organ of male and female mice. We first analyzed the temporal properties of AOB projection neurons and demonstrated that neurons display prolonged, variable, and neuron-specific characteristics. We then analyzed various decoding schemes using AOB population responses. We showed that compared with the simplest scheme (i.e., integration of spike counts over the entire response period), the division of this period into smaller temporal bins actually yields poorer decoding accuracy. However, optimal classification accuracy can be achieved well before the end of the response period by integrating spike counts within temporally defined windows. Since VNS stimulus uptake is variable, we analyzed decoding using limited information about stimulus uptake time, and showed that with enough neurons, such time-invariant decoding is feasible. Finally, we conducted simulations that demonstrated that, unlike the main olfactory bulb, the temporal features of AOB neurons disfavor decoding with high temporal accuracy, and, rather, support decoding without precise knowledge of stimulus uptake time. SIGNIFICANCE STATEMENT A key goal in sensory system research is to identify which metrics of neuronal activity are relevant for decoding stimulus features. Here, we describe the first systematic analysis of temporal coding in the vomeronasal system (VNS), a chemosensory system devoted to socially relevant cues. Compared with the main olfactory system, timescales of VNS function are inherently slower and variable. Using various analyses of real and simulated data, we show that the consideration of response times relative to stimulus uptake can aid the decoding of stimulus information from neuronal activity. However, response properties of accessory olfactory bulb neurons favor decoding schemes that do not rely on the precise timing of stimulus uptake. Such schemes are consistent with the variable nature of VNS stimulus uptake. Copyright © 2018 the authors 0270-6474/18/384957-20$15.00/0.

A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons

PubMed Central

Chung, Paul Chu Sin; Keyworth, Helen L.; Martin-Garcia, Elena; Charbogne, Pauline; Darcq, Emmanuel; Bailey, Alexis; Filliol, Dominique; Matifas, Audrey; Ouagazzal, Abdel-Mouttalib; Gaveriaux-Ruff, Claire; Befort, Katia; Maldonado, Rafael; Kitchen, Ian; Kieffer, Brigitte L.

2014-01-01

Background The delta opioid receptor (DOR) is broadly expressed throughout the nervous system and regulates chronic pain, emotional responses, motivation and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. Here we used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain. Methods We characterized DOR distribution in the brain of Dlx5/6-CreXOprd1fl/fl (Dlx-DOR) mice, and tested main central DOR functions through behavioral testing. Results DORs proteins were strongly deleted in olfactory bulb and striatum, and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. Furthermore, Dlx-DOR mice showed lower levels of anxiety in the elevated plus-maze, opposing the known high anxiety in constitutive DOR knockout animals. Also Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding (NSF) task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos staining after NSF was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice. Conclusion Here we demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. DORs therefore exert dual anxiolytic/anxiogenic roles in emotional responses, which may both have implications in the area of anxiety disorders. PMID:25444168

Anatomical and functional analysis of domestication effects on the olfactory system of the silkmoth Bombyx mori

PubMed Central

Bisch-Knaden, Sonja; Daimon, Takaaki; Shimada, Toru; Hansson, Bill S.; Sachse, Silke

2014-01-01

The silkmoth Bombyx mori is the main producer of silk worldwide and has furthermore become a model organism in biological research, especially concerning chemical communication. However, the impact domestication might have had on the silkmoth's olfactory sense has not yet been investigated. Here, we show that the pheromone detection system in B. mori males when compared with their wild ancestors Bombyx mandarina seems to have been preserved, while the perception of environmental odorants in both sexes of domesticated silkmoths has been degraded. In females, this physiological impairment was mirrored by a clear reduction in olfactory sensillum numbers. Neurophysiological experiments with hybrids between wild and domesticated silkmoths suggest that the female W sex chromosome, so far known to have the sole function of determining femaleness, might be involved in the detection of environmental odorants. Moreover, the coding of odorants in the brain, which is usually similar among closely related moths, differs strikingly between B. mori and B. mandarina females. These results indicate that domestication has had a strong impact on odour detection and processing in the olfactory model species B. mori. PMID:24258720

Molecular Communication over Gas Stream Channels using Portable Mass Spectrometry.

PubMed

Giannoukos, Stamatios; Marshall, Alan; Taylor, Stephen; Smith, Jeremy

2017-11-01

The synthetic generation/coding and transmission of olfactory information over a gas stream or an odor network is a new and unexplored field. Application areas vary from the entertainment or advertisement industry to security and telemedicine. However, current technological limitations frustrate the accurate reproduction of decoded and transmitted olfactory data. This study describes the development, testing, and characterization of a novel odor emitter (OE) that is used to investigate the generation-encoding of gaseous standards with odorous characteristics with a regulatable way, for scent transmission purposes. The calibration and the responses of a developed OE were examined using a portable quadrupole mass spectrometer (MS). Experiments were undertaken for a range of volatile organic compounds (VOCs) at different temperatures and flow rates. Individual compounds and mixtures were tested to investigate periodic and dynamic transmission characteristics within two different size tubular containers for distances up to 3 m. Olfactory information transmission is demonstrated using MS as the main molecular sensor for odor detection and monitoring and for the first time spatial encryption of olfactory information is shown. Graphical Abstract ᅟ.

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

PubMed

Piarulli, A; Zaccaro, A; Laurino, M; Menicucci, D; De Vito, A; Bruschini, L; Berrettini, S; Bergamasco, M; Laureys, S; Gemignani, A

2018-04-26

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject's behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

Anatomical and functional analysis of domestication effects on the olfactory system of the silkmoth Bombyx mori.

PubMed

Bisch-Knaden, Sonja; Daimon, Takaaki; Shimada, Toru; Hansson, Bill S; Sachse, Silke

2014-01-07

The silkmoth Bombyx mori is the main producer of silk worldwide and has furthermore become a model organism in biological research, especially concerning chemical communication. However, the impact domestication might have had on the silkmoth's olfactory sense has not yet been investigated. Here, we show that the pheromone detection system in B. mori males when compared with their wild ancestors Bombyx mandarina seems to have been preserved, while the perception of environmental odorants in both sexes of domesticated silkmoths has been degraded. In females, this physiological impairment was mirrored by a clear reduction in olfactory sensillum numbers. Neurophysiological experiments with hybrids between wild and domesticated silkmoths suggest that the female W sex chromosome, so far known to have the sole function of determining femaleness, might be involved in the detection of environmental odorants. Moreover, the coding of odorants in the brain, which is usually similar among closely related moths, differs strikingly between B. mori and B. mandarina females. These results indicate that domestication has had a strong impact on odour detection and processing in the olfactory model species B. mori.

Molecular Communication over Gas Stream Channels using Portable Mass Spectrometry

NASA Astrophysics Data System (ADS)

Giannoukos, Stamatios; Marshall, Alan; Taylor, Stephen; Smith, Jeremy

2017-07-01

The synthetic generation/coding and transmission of olfactory information over a gas stream or an odor network is a new and unexplored field. Application areas vary from the entertainment or advertisement industry to security and telemedicine. However, current technological limitations frustrate the accurate reproduction of decoded and transmitted olfactory data. This study describes the development, testing, and characterization of a novel odor emitter (OE) that is used to investigate the generation-encoding of gaseous standards with odorous characteristics with a regulatable way, for scent transmission purposes. The calibration and the responses of a developed OE were examined using a portable quadrupole mass spectrometer (MS). Experiments were undertaken for a range of volatile organic compounds (VOCs) at different temperatures and flow rates. Individual compounds and mixtures were tested to investigate periodic and dynamic transmission characteristics within two different size tubular containers for distances up to 3 m. Olfactory information transmission is demonstrated using MS as the main molecular sensor for odor detection and monitoring and for the first time spatial encryption of olfactory information is shown.

Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

PubMed

Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

2018-04-15

In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of the Drosophila lateral horn in olfactory information processing and behavioral response.

PubMed

Schultzhaus, Janna N; Saleem, Sehresh; Iftikhar, Hina; Carney, Ginger E

2017-04-01

Animals must rapidly and accurately process environmental information to produce the correct behavioral responses. Reactions to previously encountered as well as to novel but biologically important stimuli are equally important, and one understudied region in the insect brain plays a role in processing both types of stimuli. The lateral horn is a higher order processing center that mainly processes olfactory information and is linked via olfactory projection neurons to another higher order learning center, the mushroom body. This review focuses on the lateral horn of Drosophila where most functional studies have been performed. We discuss connectivity between the primary olfactory center, the antennal lobe, and the lateral horn and mushroom body. We also present evidence for the lateral horn playing roles in innate behavioral responses by encoding biological valence to novel odor cues and in learned responses to previously encountered odors by modulating neural activity within the mushroom body. We describe how these processes contribute to acceptance or avoidance of appropriate or inappropriate mates and food, as well as the identification of predators. The lateral horn is a sexually dimorphic and plastic region of the brain that modulates other regions of the brain to ensure that insects produce rapid and effective behavioral responses to both novel and learned stimuli, yet multiple gaps exist in our knowledge of this important center. We anticipate that future studies on olfactory processing, learning, and innate behavioral responses will include the lateral horn in their examinations, leading to a more comprehensive understanding of olfactory information relay and resulting behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical limits to autofluorescence signals in vivo recordings in the rat olfactory bulb: a Monte Carlo study

NASA Astrophysics Data System (ADS)

L'Heureux, B.; Gurden, H.; Pinot, L.; Mastrippolito, R.; Lefebvre, F.; Lanièce, P.; Pain, F.

2007-07-01

Understanding the cellular mechanisms of energy supply to neurons following physiological activation is still challenging and has strong implications to the interpretation of clinical functional images based on metabolic signals such as Blood Oxygen Level Dependent Magnetic Resonance Imaging or 18F-Fluorodexoy-Glucose Positron Emission Tomography. Intrinsic Optical Signal Imaging provides with high spatio temporal resolution in vivo imaging in the anaesthetized rat. In that context, intrinsic signals are mainly related to changes in the optical absorption of haemoglobin depending on its oxygenation state. This technique has been validated for imaging of the rat olfactory bulb, providing with maps of the actived olfactory glomeruli, the functional modules involved in the first step of olfactory coding. A complementary approach would be autofluorescence imaging relying on the fluorescence properties of endogenous Flavin Adenine Dinucleotide (FAD) or Nicotinamide Adenine Dinucleotide (NADH) both involved in intracellular metabolic pathways. The purpose of the present study was to investigate the feasibility of in vivo autofluorescence imaging in the rat olfactory bulb. We performed standard Monte Carlo simulations of photons scattering and absorption at the excitation and emission wavelengths of FAD and NADH fluorescence. Characterization of the fluorescence distribution in the glomerulus, effect of hemoglobin absorption at the excitation and absorption wavelengths as well as the effect of the blurring due to photon scattering and the depth of focus of the optical apparatus have been studied. Finally, optimal experimental parameters are proposed to achieve in vivo validation of the technique in the rat olfactory bulb.

The vomeronasal cortex - afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice.

PubMed

Gutiérrez-Castellanos, Nicolás; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2014-01-01

Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that the posteromedial cortical nucleus of the amygdala is strongly interconnected not only with the rest of the vomeronasal system (AOB and its target structures in the amygdala), but also with the olfactory system (piriform cortex, olfactory-recipient nuclei of the amygdala and entorhinal cortex). Therefore, the posteromedial cortical nucleus of the amygdala probably integrates olfactory and vomeronasal information. In addition, the posteromedial cortical nucleus of the amygdala shows moderate interconnections with the associative (basomedial) amygdala and with the ventral hippocampus, which may be involved in emotional and spatial learning (respectively) induced by chemical signals. Finally, the posteromedial cortical nucleus of the amygdala gives rise to zinc-enriched projections to the ventrolateral septum and the ventromedial striatum (including the medial islands of Calleja). This pattern of intracortical connections (with the olfactory cortex and hippocampus, mainly) and cortico-striatal excitatory projections (with the olfactory tubercle and septum) is consistent with its proposed nature as the primary vomeronasal cortex. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

PubMed Central

Tabor, Rico; Friedrich, Rainer W.

2008-01-01

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb. PMID:18183297

Cross-adaptation between Olfactory Responses Induced by Two Subgroups of Odorant Molecules

PubMed Central

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-01-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at −54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 ± 7 mV (mean ± SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:12939391

Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

PubMed

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-09-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

Calmodulin-regulated adenylyl cyclases and neuromodulation.

PubMed

Xia, Z; Storm, D R

1997-06-01

Coincidence detection and crosstalk between signal transduction systems play very important regulatory roles in the nervous system, particularly in the regulation of transcription. Coupling of the Ca2+ and cAMP regulatory systems by calmodulin-regulated adenylyl cyclases is hypothesized to be important for some forms of synaptic plasticity, neuroendocrine function, and olfactory detection. Recent studies of a mutant mouse deficient in type I calmodulin-sensitive adenylyl cyclase have provided the first evidence that adenylyl cyclases are important for synaptic plasticity, as well as for learning and memory in vertebrates.

Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

PubMed Central

Figueres-Oñate, Maria; López-Mascaraque, Laura

2016-01-01

Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

Home-cage odors spatial cues elicit theta phase/gamma amplitude coupling between olfactory bulb and dorsal hippocampus.

PubMed

Pena, Roberta Ribas; Medeiros, Daniel de Castro; Guarnieri, Leonardo de Oliveira; Guerra, Julio Boriollo; Carvalho, Vinícius Rezende; Mendes, Eduardo Mazoni Andrade Marçal; Pereira, Grace Schenatto; Moraes, Márcio Flávio Dutra

2017-11-05

The brain oscillations may play a critical role in synchronizing neuronal assemblies in order to establish appropriate sensory-motor integration. In fact, studies have demonstrated phase-amplitude coupling of distinct oscillatory rhythms during cognitive processes. Here we investigated whether olfacto-hippocampal coupling occurs when mice are detecting familiar odors located in a spatially restricted area of a new context. The spatial olfactory task (SOT) was designed to expose mice to a new environment in which only one quadrant (target) contains odors provided by its own home-cage bedding. As predicted, mice showed a significant higher exploration preference to the target quadrant; which was impaired by olfactory epithelium lesion (ZnSO 4 ). Furthermore, mice were able to discriminate odors from a different cage and avoided the quadrant with predator odor 2,4,5-trimethylthiazoline (TMT), reinforcing the specificity of the SOT. The local field potential (LFP) analysis of non-lesioned mice revealed higher gamma activity (35-100Hz) in the main olfactory bulb (MOB) and a significant theta phase/gamma amplitude coupling between MOB and dorsal hippocampus, only during exploration of home-cage odors (i.e. in the target quadrant). Our results suggest that exploration of familiar odors in a new context involves dynamic coupling between the olfactory bulb and dorsal hippocampus. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Odourant dominance in olfactory mixture processing: what makes a strong odourant?

PubMed Central

Schubert, Marco; Sandoz, Jean-Christophe; Galizia, Giovanni; Giurfa, Martin

2015-01-01

The question of how animals process stimulus mixtures remains controversial as opposing views propose that mixtures are processed analytically, as the sum of their elements, or holistically, as unique entities different from their elements. Overshadowing is a widespread phenomenon that can help decide between these alternatives. In overshadowing, an individual trained with a binary mixture learns one element better at the expense of the other. Although element salience (learning success) has been suggested as a main explanation for overshadowing, the mechanisms underlying this phenomenon remain unclear. We studied olfactory overshadowing in honeybees to uncover the mechanisms underlying olfactory-mixture processing. We provide, to our knowledge, the most comprehensive dataset on overshadowing to date based on 90 experimental groups involving more than 2700 bees trained either with six odourants or with their resulting 15 binary mixtures. We found that bees process olfactory mixtures analytically and that salience alone cannot predict overshadowing. After normalizing learning success, we found that an unexpected feature, the generalization profile of an odourant, was determinant for overshadowing. Odourants that induced less generalization enhanced their distinctiveness and became dominant in the mixture. Our study thus uncovers features that determine odourant dominance within olfactory mixtures and allows the referring of this phenomenon to differences in neural activity both at the receptor and the central level in the insect nervous system. PMID:25652840

In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles.

PubMed

Assié, Marie-Bernadette; Dominguez, Hélène; Consul-Denjean, Nathalie; Newman-Tancredi, Adrian

2006-09-01

Interaction with dopamine D2-like receptors plays a major role in the therapeutic effects of antipsychotic drugs. We examined in vivo dopamine D2 receptor occupancy of various established and potential antipsychotics in mouse striatum and olfactory tubercles 1 h after administration of the compound, using [3H]nemonapride as a ligand. All the compounds reduced in vivo binding of [3H]nemonapride in the striatum. When administered systemically, conventional antipsychotics, D2 antagonists, nemonapride (ID50: 0.034 mg/kg), eticlopride (0.047), haloperidol (0.11) and raclopride (0.11) potently inhibited [3H]nemonapride binding. The 'atypical' antipsychotics, risperidone (0.18), ziprasidone (0.38), aripiprazole (1.6), olanzapine (0.99), and clozapine (11.1) were less potent for occupying D2-like receptors. New compounds, displaying marked agonism at 5-HT1A receptors in addition to D2 receptor affinity, exhibited varying D2 receptor occupancy: bifeprunox (0.25), SLV313 (0.78), SSR181507 (1.6) and sarizotan (6.7). ID50 values for inhibition of [3H]nemonapride binding in the striatum correlated with those in the olfactory tubercles (r=0.95, P<0.0001). These values also correlated with previously-reported in vitro affinity of the compounds at rat D2 receptors (r=0.85, P=0.0001) and with inhibition of apomorphine-induced climbing in mice (r=0.79 P=0.0005). In contrast, there was no significant correlation between ID50 values herein and previously-reported ED50 values for catalepsy in mice. These data indicate that: (1) there is no difference in D2 receptor occupancy in limbic versus striatal regions between most classical and atypical or potential antipsychotics; and (2) high occupancy of D2 receptors can be dissociated from catalepsy, if the drugs also activate 5-HT1A receptors. Taken together, these data support the strategy of simultaneously targeting D2 receptor blockade and 5-HT1A receptor activation for new antipsychotics.

Vomeronasal versus olfactory epithelium: is there a cellular basis for human vomeronasal perception?

PubMed

Witt, Martin; Hummel, Thomas

2006-01-01

The vomeronasal organ (VNO) constitutes an accessory olfactory organ that receives chemical stimuli, pheromones, which elicit behavioral, reproductive, or neuroendocrine responses among individuals of the same species. In many macrosmatic animals, the morphological substrate constitutes a separate organ system consisting of a vomeronasal duct (ductus vomeronasalis, VND), equipped with chemosensory cells, and a vomeronasal nerve (nervus vomeronasalis, VNN) conducting information into the accessory olfactory bulb (AOB) in the central nervous system (CNS). Recent data require that the long-accepted dual functionality of a main olfactory system and the VNO be reexamined, since all species without a VNO are nevertheless sexually active, and species possessing a VNO also can sense other than "vomeronasal" stimuli via the vomeronasal epithelium (VNE). The human case constitutes a borderline situation, as its embryonic VNO anlage exerts a developmental track common to most macrosmatics, but later typical structures such as the VNN, AOB, and probably most of the chemoreceptor cells within the still existent VND are lost. This review also presents recent information on the VND including immunohistochemical expression of neuronal markers, intermediate filaments, lectins, integrins, caveolin, CD44, and aquaporins. Further, we will address the issue of human pheromone candidates.

Combinatorial Codes and Labeled Lines: How Insects Use Olfactory Cues to Find and Judge Food, Mates, and Oviposition Sites in Complex Environments

PubMed Central

Haverkamp, Alexander; Hansson, Bill S.; Knaden, Markus

2018-01-01

Insects, including those which provide vital ecosystems services as well as those which are devastating pests or disease vectors, locate their resources mainly based on olfaction. Understanding insect olfaction not only from a neurobiological but also from an ecological perspective is therefore crucial to balance insect control and conservation. However, among all sensory stimuli olfaction is particularly hard to grasp. Our chemical environment is made up of thousands of different compounds, which might again be detected by our nose in multiple ways. Due to this complexity, researchers have only recently begun to explore the chemosensory ecology of model organisms such as Drosophila, linking the tools of chemical ecology to those of neurogenetics. This cross-disciplinary approach has enabled several studies that range from single odors and their ecological relevance, via olfactory receptor genes and neuronal processing, up to the insects' behavior. We learned that the insect olfactory system employs strategies of combinatorial coding to process general odors as well as labeled lines for specific compounds that call for an immediate response. These studies opened new doors to the olfactory world in which insects feed, oviposit, and mate. PMID:29449815

Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid.

PubMed

Thach, Trung Thanh; Hong, Yu-Jung; Lee, Sangho; Lee, Sung-Joon

2017-04-01

The mouse olfactory receptor Olfr544 is expressed in several non-olfactory tissues and has been suggested as a functional receptor regulating different signaling pathways. However, the molecular interaction between Olfr544 and its natural ligand, azelaic acid (AzA), remains poorly characterized, primarily due to difficulties in the heterologous expression of the receptor protein on the cell membrane and lack of entire protein structure. In this report, we describe the molecular determinants of Olfr544 activation by AzA. N-terminal lucy-flag-rho tag ensured the heterologous expression of Olfr544 on the Hana3A cell surface. Molecular modeling and docking combined with mutational analysis identified amino acid residues in the Olfr544 for the interaction with AzA. Our data demonstrated that the Y109 residue in transmembrane helix 3 forms a hydrogen bond with AzA, which is crucial for the receptor-ligand interaction and activation. Y109 is required for the Olfr544 activation by AzA which, in turn, stimulates the Olfr544-dependent CREB-PGC-1α signaling axis and is followed by the induction of mitochondrial biogenesis in Olfr544 wild-type transfected Hana3A cells, but not in mock or Y109A mutant transfected cells. Collectively, these data indicated that a hydrogen bond between Y109 residue and AzA is a major determinant of the Olfr544-AzA interaction and activation. Copyright © 2017 Elsevier Inc. All rights reserved.

Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells

PubMed Central

Liu, Shaolin; Plachez, Celine; Shao, Zuoyi; Puche, Adam; Shipley, Michael T.

2013-01-01

Evidence for co-expression of two or more classic neurotransmitters in neurons has increased but less is known about co-transmission. Ventral tegmental area (VTA) neurons, co-release dopamine (DA), the excitatory transmitter glutamate and the inhibitory transmitter GABA onto target cells in the striatum. Olfactory bulb (OB) short axon cells (SACs) form interglomerular connections and co-express markers for dopamine (DA) and GABA. Using an optogenetic approach we provide evidence that mouse OB SACs release both GABA and DA onto external tufted cells (ETCs) in other glomeruli. Optical activation of channelrhodopsin specifically expressed in DAergic SACs produced a GABAA receptor-mediated monosynaptic inhibitory response followed by DA-D1-like receptor-mediated excitatory response in ETCs. The GABAA receptor-mediated hyperpolarization activates Ih current in ETCs; synaptically released DA increases Ih, which enhances post-inhibitory rebound spiking. Thus, the opposing actions of synaptically released GABA and DA are functionally integrated by Ih to generate an inhibition-to-excitation “switch” in ETCs. Consistent with the established role of Ih in ETC burst firing, we show that endogenous DA release increases ETC spontaneous bursting frequency. ETCs transmit sensory signals to mitral/tufted output neurons and drive intraglomerular inhibition to shape glomerulus output to downstream olfactory networks. GABA and DA co-transmission from SACs to ETCs may play a key role in regulating output coding across the glomerular array. PMID:23407950

Ecological adaptation determines functional mammalian olfactory subgenomes

PubMed Central

Hayden, Sara; Bekaert, Michaël; Crider, Tess A.; Mariani, Stefano; Murphy, William J.; Teeling, Emma C.

2010-01-01

The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families. PMID:19952139

Sensing the Underground – Ultrastructure and Function of Sensory Organs in Root-Feeding Melolontha melolontha (Coleoptera: Scarabaeinae) Larvae

PubMed Central

Hansson, Bill S.; Hilker, Monika; Reinecke, Andreas

2012-01-01

Introduction Below ground orientation in insects relies mainly on olfaction and taste. The economic impact of plant root feeding scarab beetle larvae gave rise to numerous phylogenetic and ecological studies. Detailed knowledge of the sensory capacities of these larvae is nevertheless lacking. Here, we present an atlas of the sensory organs on larval head appendages of Melolontha melolontha. Our ultrastructural and electrophysiological investigations allow annotation of functions to various sensory structures. Results Three out of 17 ascertained sensillum types have olfactory, and 7 gustatory function. These sensillum types are unevenly distributed between antennae and palps. The most prominent chemosensory organs are antennal pore plates that in total are innervated by approximately one thousand olfactory sensory neurons grouped into functional units of three-to-four. In contrast, only two olfactory sensory neurons innervate one sensillum basiconicum on each of the palps. Gustatory sensilla chaetica dominate the apices of all head appendages, while only the palps bear thermo-/hygroreceptors. Electrophysiological responses to CO2, an attractant for many root feeders, are exclusively observed in the antennae. Out of 54 relevant volatile compounds, various alcohols, acids, amines, esters, aldehydes, ketones and monoterpenes elicit responses in antennae and palps. All head appendages are characterized by distinct olfactory response profiles that are even enantiomer specific for some compounds. Conclusions Chemosensory capacities in M. melolontha larvae are as highly developed as in many adult insects. We interpret the functional sensory units underneath the antennal pore plates as cryptic sensilla placodea and suggest that these perceive a broad range of secondary plant metabolites together with CO2. Responses to olfactory stimulation of the labial and maxillary palps indicate that typical contact chemo-sensilla have a dual gustatory and olfactory function. PMID:22848471

Predictors of quality of life outcomes in chronic rhinosinusitis after sinus surgery.

PubMed

Katotomichelakis, Michael; Simopoulos, Efthimios; Tripsianis, Gregory; Balatsouras, Dimitrios; Danielides, Gerasimos; Kourousis, Christos; Livaditis, Miltos; Danielides, Vassilios

2014-04-01

The predictive value of olfaction for quality of life (QoL) recovery after endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) is still underestimated. The aim of this study was to explore the proportion of patients suffering from CRS who experience clinically significant QoL improvement after ESS and identify pre-operative clinical phenotypes that best predict surgical outcomes for QoL, focusing mainly on the role of patients' olfaction. One hundred eleven patients following ESS for CRS and 48 healthy subjects were studied. Olfactory function was expressed by the combined "Threshold Discrimination Identification" score using "Sniffin' sticks" test pre-treatment and 12 months after treatment. All subjects completed validated, widely used QoL questionnaires, specific for olfaction (Questionnaire of Olfactory Deficits: QOD), for assessing psychology (Beck Depression Inventory: BDI) and for general health (Short Form-36: SF-36). Statistically significant improvement of olfactory function by 41.8% and of all QoL questionnaires scores (all p < 0.001) was observed on the 12-month follow-up examination. Clinically significant improvement for QoL was measured in a proportion of 56.8% of patients on QOD, 64.9% on SF-36 and 49.5% on BDI scales results. Although olfactory dysfunction, nasal polyps, female gender, high socio-economic status and non-smoking habits were significantly associated with better QoL results, multivariate logistic regression analysis revealed that only olfactory dysfunction and nasal polyps were independent predictors significantly associated with higher likelihood of clinically significant improvement in all QoL questionnaire results. Olfactory dysfunction and nasal polyps were independent pre-operative predictors for surgical outcomes with regard to QoL results.

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

Comparison of odor and mating-induced glomerular activation in the main olfactory bulb of estrous female ferrets.

PubMed

Batterton, M N; Robarts, D; Woodley, S K; Baum, M J

2006-06-12

Previously [S.K. Woodley, M.J. Baum, Differential activation of glomeruli in the ferret's main olfactory bulb by anal scent gland odors from males and females: an early step in mate identification, Eur. J. Neurosci. 20 (2004) 1025-1032], the receipt of intromission from a male activated glomeruli (indexed by Fos immunoreactivity in juxtaglomerular cells) in the main olfactory bulb (MOB) of estrous female ferrets which exceeded the activation seen after exposure to male anal scent gland odorants alone. We asked whether centrifugal inputs (e.g., from the locus coeruleus to the MOB) generated by the receipt of vaginal-cervical stimulation influence odor-induced MOB glomerular activation. We compared the activation of MOB glomeruli in estrous female ferrets which received a unilateral naris occlusion prior to exposure to: unscented air, volatile odorants from an anesthetized male, volatile + non-volatile odorants from direct physical contact with an anesthetized male, or mating stimulation. Little glomerular activation was observed in the MOB ipsilateral to an occluded naris, including females which received intromission. An equivalent distribution of activated glomeruli was observed in the ventral MOB of estrous females which either received mating stimulation or had direct physical contact with an anesthetized male. Considerably less glomerular activation occurred in females exposed only to volatile male odors. The MOB of female ferrets responded to body odorants from the opposite sex; however, there was no evidence that mating-induced centrifugal inputs directly activated MOB glomeruli or modified odor-induced glomerular activation.

Does the cycad genotoxin MAM implicated in Guam ALS-PDC induce disease-relevant changes in mouse brain that includes olfaction?

PubMed

Kisby, Glen; Palmer, Valerie; Lasarev, Mike; Fry, Rebecca; Iordanov, Mihail; Magun, Eli; Samson, Leona; Spencer, Peter

2011-11-01

Western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC), a prototypical neurodegenerative disease (tauopathy) affecting distinct genetic groups with common exposure to neurotoxic chemicals in cycad seed, has many features of Parkinson's and Alzheimer's diseases (AD), including early olfactory dysfunction. Guam ALS-PDC incidence correlates with cycad flour content of cycasin and its aglycone methylazoxymethanol (MAM), which produces persistent DNA damage (O(6)-methylguanine) in the brains of mice lacking O(6)-methylguanine methyltransferase (Mgmt(-/-)). We described in Mgmt(-/-)mice up to 7 days post-MAM treatment that brain DNA damage was linked to brain gene expression changes found in human neurological disease, cancer, and skin and hair development. This addendum reports 6 months post-MAM treatment- related brain transcriptional changes as well as elevated mitogen activated protein kinases and increased caspase-3 activity, both of which are involved in tau aggregation and neurofibrillary tangle formation typical of ALS-PDC and AD, plus transcriptional changes in olfactory receptors. Does cycasin act as a "slow (geno)toxin" in ALS-PDC?

Bis(arylvinyl)pyrazines, -pyrimidines, and -pyridazines as imaging agents for tau fibrils and β-amyloid plaques in Alzheimer's disease models.

PubMed

Boländer, Alexander; Kieser, Daniel; Voss, Constantin; Bauer, Silvia; Schön, Christian; Burgold, Steffen; Bittner, Tobias; Hölzer, Jana; Heyny-von Haußen, Roland; Mall, Gerhard; Goetschy, Valérie; Czech, Christian; Knust, Henner; Berger, Robert; Herms, Jochen; Hilger, Ingrid; Schmidt, Boris

2012-11-08

The in vivo diagnosis of Alzheimer's disease (AD) is of high socioeconomic interest and remains a demanding field of research. The biopathological hallmarks of the disease are extracellular plaques consisting of aggregated β-amyloid peptides (Aβ) and tau protein derived intracellular tangles. Here we report the synthesis and evaluation of fluorescent pyrazine, pyrimidine,and pyridazine derivatives in vitro and in vivo aiming at a tau-based diagnosis of AD. The probes were pre-evaluated on human brain tissue by fluorescence microscopy and were found to label all known disease-related alterations at high contrast and specificity. To quantify the binding affinity, a new thiazine red displacement assay was developed and selected candidates were toxicologically profiled. The application in transgenic mouse models demonstrated bioavailability and brain permeability for one compound. In the course of histological testing, we discovered an AD-related deposition of tau aggregates in the Bowman's glands of the olfactory epithelium, which holds potential for an endoscopic diagnosis of AD in the olfactory system.

Protein tyrosine phosphatase receptor type R deficient mice exhibit increased exploration in a new environment and impaired novel object recognition memory.

PubMed

Erkens, Mirthe; Bakker, Brenda; van Duijn, Lucette M; Hendriks, Wiljan J A J; Van der Zee, Catharina E E M

2014-05-15

Mouse gene Ptprr encodes multiple protein tyrosine phosphatase receptor type R (PTPRR) isoforms that negatively regulate mitogen-activated protein kinase (MAPK) signaling pathways. In the mouse brain, PTPRR proteins are expressed in cerebellum, olfactory bulb, hippocampus, amygdala and perirhinal cortex but their precise role in these regions remains to be determined. Here, we evaluated phenotypic consequences of loss of PTPRR activity and found that basal smell was normal for Ptprr(-/-) mice. Also, spatial learning and fear-associated contextual learning were unaffected. PTPRR deficiency, however, resulted in impaired novel object recognition and a striking increase in exploratory activity in a new environment. The data corroborate the importance of proper control of MAPK signaling in cerebral functions and put forward PTPRR as a novel target to modulate synaptic processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb.

PubMed

Puopolo, Michelino; Bean, Bruce P; Raviola, Elio

2005-11-01

We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current-clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking because blocking the current with ZD 7288 or Cs+ had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action-potential-clamp experiments using records of pacemaking as voltage command in voltage-clamp experiments. We found that substantial TTX-sensitive Na+ current flows during the interspike depolarization. In addition, substantial Ca2+ current flowed during the interspike interval, and blocking Ca2+ current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.

Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

PubMed

Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

2012-01-01

Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes.

Neuropeptide Y Enhances Olfactory Mucosa Responses to Odorant in Hungry Rats

PubMed Central

Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

2012-01-01

Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes. PMID:23024812

Odor preference and olfactory memory are impaired in Olfaxin-deficient mice.

PubMed

Islam, Saiful; Ueda, Masashi; Nishida, Emika; Wang, Miao-Xing; Osawa, Masatake; Lee, Dongsoo; Itoh, Masanori; Nakagawa, Kiyomi; Tana; Nakagawa, Toshiyuki

2018-06-01

Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice (Prune2 Ex16-/- ; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon of Olfaxin mRNA was deleted. Exon 16 has 80 nucleotides and is contained in four of five Prune2 isoforms, including PRUNE2, BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels of Olfaxin mRNA and Olfaxin protein in the OB and piriform cortex of KO mice significantly decreased. Although Prune2 mRNA also significantly decreased in the spinal cord, the gross anatomy of the spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of the sensory and motor system was not observed in KO mice. Therefore, in the current study, we examined the role of Olfaxin in the olfactory system where PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in KO mice using opposite-sex urinary scents as well as a non-social odor stimulus (almond). Results of the odor-aversion test demonstrated that odor-associative learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch in the piriform cortex was not observed in KO mice. These results indicated that Olfaxin may play a critical role in odor preference and olfactory memory. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaulation of cancer and non-cancer effects of cumene ...

EPA Pesticide Factsheets

Cumene, also known as isopropyl benzene, is a volatile liquid. We have systematically reviewed published literature to evaluate cancer and noncancer effects of cumene. Cumene, readily absorbed via inhalation is distributed in several tissues, metabolized extensively by cytochrome P-450 isozymes within hepatic and extra-hepatic tissues and excreted through urine. Although, there are no epidemiological cancer studies for humans, chronic inhalation exposure studies in rat and mouse have shown increased nasal lesions including atrophy, basal cell hyperplasia, atypical hyperplasia and hyperplasia of the olfactory epithelium glands. To present the information at the Society of Toxicology Meeting.

Frequency transitions in odor-evoked neural oscillations

PubMed Central

Ito, Iori; Bazhenov, Maxim; Ong, Rose Chik-ying; Raman, Baranidharan; Stopfer, Mark

2009-01-01

Summary In many species sensory stimuli elicit the oscillatory synchronization of groups of neurons. What determines the properties of these oscillations? In the olfactory system of the moth we found that odors elicited oscillatory synchronization through a neural mechanism like that described in locust and Drosophila. During responses to long odor pulses, oscillations suddenly slowed as net olfactory receptor neuron (ORN) output decreased; thus, stimulus intensity appeared to determine oscillation frequency. However, changing the concentration of the odor had little effect upon oscillatory frequency. Our recordings in vivo and computational models based on these results suggested the main effect of increasing odor concentration was to recruit additional, less well-tuned ORNs whose firing rates were tightly constrained by adaptation and saturation. Thus, in the periphery, concentration is encoded mainly by the size of the responsive ORN population, and oscillation frequency is set by the adaptation and saturation of this response. PMID:20005825

Frequency transitions in odor-evoked neural oscillations.

PubMed

Ito, Iori; Bazhenov, Maxim; Ong, Rose Chik-ying; Raman, Baranidharan; Stopfer, Mark

2009-12-10

In many species, sensory stimuli elicit the oscillatory synchronization of groups of neurons. What determines the properties of these oscillations? In the olfactory system of the moth, we found that odors elicited oscillatory synchronization through a neural mechanism like that described in locust and Drosophila. During responses to long odor pulses, oscillations suddenly slowed as net olfactory receptor neuron (ORN) output decreased; thus, stimulus intensity appeared to determine oscillation frequency. However, changing the concentration of the odor had little effect upon oscillatory frequency. Our recordings in vivo and computational models based on these results suggested that the main effect of increasing odor concentration was to recruit additional, less well-tuned ORNs whose firing rates were tightly constrained by adaptation and saturation. Thus, in the periphery, concentration is encoded mainly by the size of the responsive ORN population, and oscillation frequency is set by the adaptation and saturation of this response.

Crypt cells are involved in kin recognition in larval zebrafish

PubMed Central

Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F.

2016-01-01

Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal. PMID:27087508

Crypt cells are involved in kin recognition in larval zebrafish.

PubMed

Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F

2016-04-18

Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal.

Coactivation of Gustatory and Olfactory Signals in Flavor Perception

PubMed Central

Veldhuizen, Maria G.; Shepard, Timothy G.; Wang, Miao-Fen

2010-01-01

It is easier to detect mixtures of gustatory and olfactory flavorants than to detect either component alone. But does the detection of mixtures exceed the level predicted by probability summation, assuming independent detection of each component? To answer this question, we measured simple response times (RTs) to detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral [olfactory], sucrose–citral mixture) or water, presented into the mouth by a computer-operated, automated flow system. Subjects were instructed to press a button as soon as they detected any of the 3 nonwater stimuli. Responses to the mixtures were faster (RTs smaller) than predicted by a model of probability summation of independently detected signals, suggesting positive coactivation (integration) of gustation and retronasal olfaction in flavor perception. Evidence for integration appeared mainly in the fastest 60% of the responses, indicating that integration arises relatively early in flavor processing. Results were similar when the 3 possible flavorants, and water, were interleaved within the same session (experimental condition), and when each flavorant was interleaved with water only (control conditions). This outcome suggests that subjects did not attend selectively to one flavor component or the other in the experimental condition and further supports the conclusion that (late) decisional or attentional strategies do not exert a large influence on the gustatory–olfactory flavor integration. PMID:20032112

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

PubMed Central

Rabhi, Kaouther K.; Deisig, Nina; Demondion, Elodie; Le Corre, Julie; Robert, Guillaume; Tricoire-Leignel, Hélène; Lucas, Philippe; Gadenne, Christophe; Anton, Sylvia

2016-01-01

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids, leaving residues in the environment. There is now evidence that low doses of insecticides can have positive effects on pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction, and olfactory synaptic transmission is cholinergic, neonicotinoid residues could modify chemical communication. We recently showed that treatments with different sublethal doses of clothianidin could either enhance or decrease behavioural sex pheromone responses in the male moth, Agrotis ipsilon. We investigated now effects of the behaviourally active clothianidin doses on the sensitivity of the peripheral and central olfactory system. We show with extracellular recordings that both tested clothianidin doses do not influence pheromone responses in olfactory receptor neurons. Similarly, in vivo optical imaging does not reveal any changes in glomerular response intensities to the sex pheromone after clothianidin treatments. The sensitivity of intracellularly recorded antennal lobe output neurons, however, is upregulated by a lethal dose 20 times and downregulated by a dose 10 times lower than the lethal dose 0. This correlates with the changes of behavioural responses after clothianidin treatment and suggests the antennal lobe as neural substrate involved in clothianidin-induced behavioural changes. PMID:26842577

Anosmia leads to a loss of gray matter in cortical brain areas.

PubMed

Bitter, Thomas; Gudziol, Hilmar; Burmeister, Hartmut Peter; Mentzel, Hans-Joachim; Guntinas-Lichius, Orlando; Gaser, Christian

2010-06-01

Chronic olfactory disorders, including the complete loss of the sense of smell (anosmia), are common. Using voxel-based morphometry (VBM) in magnetic resonance imaging (MRI), structural changes in the cerebral gray matter (GM) of a group of patients with anosmia compared with a normosmic, healthy control group were evaluated. Patients with anosmia presented a significant decrease of GM volume mainly in the nucleus accumbens with adjacent subcallosal gyrus, in the medial prefrontal cortex (MPC) including the middle and anterior cingulate cortices, and in the dorsolateral prefrontal cortex (dlPFC). These areas are part of the limbic loop of the basal ganglia and except the dlPFC secondary olfactory areas. They also play an important role in many neurological diseases. Furthermore, volume decreases in smaller areas like the piriform cortex, insular cortex, orbitofrontal cortex, hippocampus, parahippocampal gyrus, supramarginal gyrus, and cerebellum could be seen. Longer disease duration was associated with a stronger atrophy in the described areas. No local increases in the GM volume could be observed. A comparison with results of an additionally executed functional MRI study on olfaction in healthy subjects was performed to evaluate the significance of the observed atrophy areas in cerebral olfactory processing. To our knowledge, this is the first study on persisting structural changes in cortical GM volume after complete olfactory loss.

Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance.

PubMed

Knott, Thomas K; Madany, Pasil A; Faden, Ashley A; Xu, Mei; Strotmann, Jörg; Henion, Timothy R; Schwarting, Gerald A

2012-07-04

The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2(-/-) mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2(-/-) neurons. Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2(-/-) mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2(-/-) olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2(-/-) mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2(-/-) olfactory neurons. Results presented here show that many odorant receptors are under-expressed in β3GnT2(-/-) mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2(-/-) mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2(-/-) mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.

A large contribution of a cyclic AMP-independent pathway to turtle olfactory transduction

PubMed Central

1994-01-01

Although multiple pathways are involved in the olfactory transduction mechanism, cAMP-dependent pathway has been considered to contribute mainly to the transduction. We examined the degree of contribution of cAMP-independent pathway to the turtle olfactory response by recording inward currents from isolated cells, nerve impulses from cilia and olfactory bulbar responses. The results obtained by the three recordings were essentially consistent with each other, but detail studies were carried out by recording the bulbar response to obtain quantitative data. Application of an odorant cocktail to the isolated olfactory neuron after injection of 1 mM cAMP from the patch pipette elicited a large inward current. Mean amplitude of inward currents evoked by the cocktail with 1 mM cAMP in the patch pipette was similar to that without cAMP in the pipette. Application of the cocktail after the response to 50 microM forskolin was adapted also induced a large inward current. Application of the odorant cocktail to the olfactory epithelium, after the response to 50 microM forskolin was adapted, brought about an appreciable increase in the impulse frequency. The bulbar response to forskolin alone reached a saturation level around 10 microM. After the response to 50 microM forskolin was adapted, 11 species of odorants were applied to the olfactory epithelium. The magnitudes of responses to the odorants after forskolin were 45-80% of those of the control responses. There was no essential difference in the degree of the suppression by forskolin between cAMP- and IP3- producing odorants classified in the rat, suggesting that certain part of the forskolin-suppressive component was brought about by nonspecific action of forskolin. Application of a membrane permeant cAMP analogue, cpt-cAMP elicited a large response, and 0.1 mM citralva after 3 mM cpt- cAMP elicited 51% of the control response which was close to the response to citralva after 50 microM forskolin. A membrane permeant cGMP analogue, db-cGMP elicited a small response and the response to 0.1 mM citralva was unaffected by db-cGMP. It was concluded that cAMP- independent (probably IP3-independent) pathway greatly contributes to the turtle olfactory transduction. PMID:7523576

Odor Discrimination in Drosophila: From Neural Population Codes to Behavior

PubMed Central

Parnas, Moshe; Lin, Andrew C.; Huetteroth, Wolf; Miesenböck, Gero

2013-01-01

Summary Taking advantage of the well-characterized olfactory system of Drosophila, we derive a simple quantitative relationship between patterns of odorant receptor activation, the resulting internal representations of odors, and odor discrimination. Second-order excitatory and inhibitory projection neurons (ePNs and iPNs) convey olfactory information to the lateral horn, a brain region implicated in innate odor-driven behaviors. We show that the distance between ePN activity patterns is the main determinant of a fly’s spontaneous discrimination behavior. Manipulations that silence subsets of ePNs have graded behavioral consequences, and effect sizes are predicted by changes in ePN distances. ePN distances predict only innate, not learned, behavior because the latter engages the mushroom body, which enables differentiated responses to even very similar odors. Inhibition from iPNs, which scales with olfactory stimulus strength, enhances innate discrimination of closely related odors, by imposing a high-pass filter on transmitter release from ePN terminals that increases the distance between odor representations. PMID:24012006

An olfactory receptor from Apolygus lucorum (Meyer-Dur) mainly tuned to volatiles from flowering host plants.

PubMed

Yan, Shu-Wei; Zhang, Jin; Liu, Yang; Li, Guo-Qing; Wang, Gui-Rong

2015-08-01

Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) is one of the most serious agricultural pests, feeding on a wide range of cultivated plants, including cotton, cereals and vegetables in the north of China. This insect can frequently switch between habitats and host plants over seasons and prefer plants in bloom. A. lucorum relies heavily on olfaction to locate its host plants finely discriminating different plant volatiles in the environment. Despite its economical importance, research on the olfactory system of this species has been so far very limited. In this study, we have identified and characterized an olfactory receptor which is sensitively tuned to (Z)-3-Hexenyl acetate and several flowering compounds. Besides being present in the bouquet of some flowers, these compounds are produced by plants that have suffered attacks and are supposed to act as chemical messengers between plants. This OR may play an important role in the selection of host plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Organization of the olfactory system of nymphalidae butterflies.

PubMed

Carlsson, Mikael A; Schäpers, Alexander; Nässel, Dick R; Janz, Niklas

2013-05-01

Olfaction is in many species the most important sense, essential for food search, mate finding, and predator avoidance. Butterflies have been considered a microsmatic group of insects that mainly rely on vision due to their diurnal lifestyle. However, an emerging number of studies indicate that butterflies indeed use the sense of smell for locating food and oviposition sites. To unravel the neural substrates for olfaction, we performed an anatomical study of 2 related butterfly species that differ in food and host plant preference. We found many of the anatomical structures and pathways, as well as distribution of neuroactive substances, to resemble that of their nocturnal relatives among the Lepidoptera. The 2 species differed in the number of one type of olfactory sensilla, thus indicating a difference in sensitivity to certain compounds. Otherwise no differences could be observed. Our findings suggest that the olfactory system in Lepidoptera is well conserved despite the long evolutionary time since butterflies and moths diverged from a common ancestor.

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome

PubMed Central

Saqran, Lubna; Herrick, Scott P.; Frosch, Matthew P.; Hyman, Bradley T.

2017-01-01

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivo. SIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo. This work describes early postnatal developmental abnormalities in visual and olfactory sensory systems in Down syndrome model mice, which provide insight into defects in the function of neural circuits in vivo and provide an approach for exploring the genetic and molecular basis for impairment in the disease. In addition, these findings raise the possibility that basic dysfunction in primary sensory circuitry may illustrate mechanisms important for global learning and cognitive impairment in Down syndrome patients. PMID:28899917

Olfactory Receptor Multigene Family in Vertebrates: From the Viewpoint of Evolutionary Genomics

PubMed Central

Niimura, Yoshihito

2012-01-01

Olfaction is essential for the survival of animals. Diverse odor molecules in the environment are detected by the olfactory receptors (ORs) in the olfactory epithelium of the nasal cavity. There are ~400 and ~1,000 OR genes in the human and mouse genomes, respectively, forming the largest multigene family in mammals. The relationships between ORs and odorants are multiple-to-multiple, which allows for discriminating almost unlimited number of different odorants by a combination of ORs. However, the OR-ligand relationships are still largely unknown, and predicting the quality of odor from its molecular structure is unsuccessful. Extensive bioinformatic analyses using the whole genomes of various organisms revealed a great variation in number of OR genes among species, reflecting the diversity of their living environments. For example, higher primates equipped with a well-developed vision system and dolphins that are secondarily adapted to the aquatic life have considerably smaller numbers of OR genes than most of other mammals do. OR genes are characterized by extremely frequent gene duplications and losses. The OR gene repertories are also diverse among human individuals, explaining the diversity of odor perception such as the specific anosmia. OR genes are present in all vertebrates. The number of OR genes is smaller in teleost fishes than in mammals, while the diversity is higher in the former than the latter. Because the genome of amphioxus, the most basal chordate species, harbors vertebrate-like OR genes, the origin of OR genes can be traced back to the common ancestor of the phylum Chordata. PMID:23024602

Hippocampal CA1 local field potential oscillations induced by olfactory cue of liked food.

PubMed

Samerphob, Nifareeda; Cheaha, Dania; Chatpun, Surapong; Kumarnsit, Ekkasit

2017-07-01

Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckpitt, Alan, E-mail: arbuckpitt@ucdavis.edu; Morin, Dexter; Murphy, Shannon

Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epitheliummore » > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.« less

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

PubMed

Midroit, Maëllie; Thevenet, Marc; Fournel, Arnaud; Sacquet, Joelle; Bensafi, Moustafa; Breton, Marine; Chalençon, Laura; Cavelius, Matthias; Didier, Anne; Mandairon, Nathalie

2018-04-22

Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas. Copyright © 2018 Elsevier B.V. All rights reserved.

Genomics of Mature and Immature Olfactory Sensory Neurons

PubMed Central

Nickell, Melissa D.; Breheny, Patrick; Stromberg, Arnold J.; McClintock, Timothy S.

2014-01-01

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors, were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes. PMID:22252456

Evolution of trace amine associated receptor (TAAR) gene family in vertebrates: lineage-specific expansions and degradations of a second class of vertebrate chemosensory receptors expressed in the olfactory epithelium.

PubMed

Hashiguchi, Yasuyuki; Nishida, Mutsumi

2007-09-01

The trace amine-associated receptors (TAARs) form a specific family of G protein-coupled receptors in vertebrates. TAARs were initially considered neurotransmitter receptors, but recent study showed that mouse TAARs function as chemosensory receptors in the olfactory epithelium. To clarify the evolutionary dynamics of the TAAR gene family in vertebrates, near-complete repertoires of TAAR genes and pseudogenes were identified from the genomic assemblies of 4 teleost fishes (zebrafish, fugu, stickleback, and medaka), western clawed frogs, chickens, 3 mammals (humans, mice, and opossum), and sea lampreys. Database searches revealed that fishes had many putatively functional TAAR genes (13-109 genes), whereas relatively small numbers of TAAR genes (3-22 genes) were identified in tetrapods. Phylogenetic analysis of these genes indicated that the TAAR gene family was subdivided into 5 subfamilies that diverged before the divergence of ray-finned fishes and tetrapods. In tetrapods, virtually all TAAR genes were located in 1 specific region of their genomes as a gene cluster; however, in fishes, TAAR genes were scattered throughout more than 2 genomic locations. This possibly reflects a whole-genome duplication that occurred in the common ancestor of ray-finned fishes. Expression analysis of zebrafish and stickleback TAAR genes revealed that many TAARs in these fishes were expressed in the olfactory organ, suggesting the relatively high importance of TAARs as chemosensory receptors in fishes. A possible evolutionary history of the vertebrate TAAR gene family was inferred from the phylogenetic and comparative genomic analyses.

Innate Predator Odor Aversion Driven by Parallel Olfactory Subsystems that Converge in the Ventromedial Hypothalamus

PubMed Central

Pérez-Gómez, Anabel; Bleymehl, Katherin; Stein, Benjamin; Pyrski, Martina; Birnbaumer, Lutz; Munger, Steven D.; Leinders-Zufall, Trese; Zufall, Frank; Chamero, Pablo

2015-01-01

Summary The existence of innate predator aversion evoked by predator-derived chemostimuli called kairomones offers a strong selective advantage for potential prey animals. However, it is unclear how chemically-diverse kairomones can elicit similar avoidance behaviors. Using a combination of behavioral analyses and single-cell Ca2+ imaging in wild-type and gene-targeted mice, we show that innate predator-evoked avoidance is driven by parallel, non-redundant processing of volatile and nonvolatile kairomones through the activation of multiple olfactory subsystems including the Grueneberg ganglion, the vomeronasal organ, and chemosensory neurons within the main olfactory epithelium. Perturbation of chemosensory responses in specific subsystems through disruption of genes encoding key sensory transduction proteins (Cnga3, Gnao1) or by surgical axotomy abolished avoidance behaviors and/or cellular Ca2+ responses to different predator odors. Stimulation of these different subsystems resulted in the activation of widely distributed target regions in the olfactory bulb, as assessed by c-Fos expression. However, in each case this c-Fos increase was observed within the same subnuclei of the medial amygdala and ventromedial hypothalamus, regions implicated in fear, anxiety and defensive behaviors. Thus, the mammalian olfactory system has evolved multiple, parallel mechanisms for kairomone detection that converge in the brain to facilitate a common behavioral response. Our findings provide significant insights into the genetic substrates and circuit logic of predator-driven, innate aversion and may serve as a valuable model for studying instinctive fear [1] and human emotional and panic disorders [2, 3]. PMID:25936549

Innate Predator Odor Aversion Driven by Parallel Olfactory Subsystems that Converge in the Ventromedial Hypothalamus.

PubMed

Pérez-Gómez, Anabel; Bleymehl, Katherin; Stein, Benjamin; Pyrski, Martina; Birnbaumer, Lutz; Munger, Steven D; Leinders-Zufall, Trese; Zufall, Frank; Chamero, Pablo

2015-05-18

The existence of innate predator aversion evoked by predator-derived chemostimuli called kairomones offers a strong selective advantage for potential prey animals. However, it is unclear how chemically diverse kairomones can elicit similar avoidance behaviors. Using a combination of behavioral analyses and single-cell Ca(2+) imaging in wild-type and gene-targeted mice, we show that innate predator-evoked avoidance is driven by parallel, non-redundant processing of volatile and nonvolatile kairomones through the activation of multiple olfactory subsystems including the Grueneberg ganglion, the vomeronasal organ, and chemosensory neurons within the main olfactory epithelium. Perturbation of chemosensory responses in specific subsystems through disruption of genes encoding key sensory transduction proteins (Cnga3, Gnao1) or by surgical axotomy abolished avoidance behaviors and/or cellular Ca(2+) responses to different predator odors. Stimulation of these different subsystems resulted in the activation of widely distributed target regions in the olfactory bulb, as assessed by c-Fos expression. However, in each case, this c-Fos increase was observed within the same subnuclei of the medial amygdala and ventromedial hypothalamus, regions implicated in fear, anxiety, and defensive behaviors. Thus, the mammalian olfactory system has evolved multiple, parallel mechanisms for kairomone detection that converge in the brain to facilitate a common behavioral response. Our findings provide significant insights into the genetic substrates and circuit logic of predator-driven innate aversion and may serve as a valuable model for studying instinctive fear and human emotional and panic disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sexual dimorphism and phenotypic plasticity in the antennal lobe of a stingless bee, Melipona scutellaris.

PubMed

Roselino, Ana Carolina; Hrncir, Michael; da Cruz Landim, Carminda; Giurfa, Martin; Sandoz, Jean-Christophe

2015-07-01

Among social insects, the stingless bees (Apidae, Meliponini), a mainly tropical group of highly eusocial bees, present an intriguing variety of well-described olfactory-dependent behaviors showing both caste- and sex-specific adaptations. By contrast, little is known about the neural structures underlying such behavioral richness or the olfactory detection and processing abilities of this insect group. This study therefore aimed to provide the first detailed description and comparison of the brains and primary olfactory centers, the antennal lobes, of the different members of a colony of the stingless bee Melipona scutellaris. Global neutral red staining, confocal laser scanning microscopy, and 3D reconstructions were used to compare the brain structures of males, workers, and virgin queens with a special emphasis on the antennal lobe. We found significant differences between both sexes and castes with regard to the relative volumes of olfactory and visual neuropils in the brain and also in the number and volume of the olfactory glomeruli. In addition, we identified one (workers, queens) and three or four (males) macroglomeruli in the antennal lobe. In both sexes and all castes, the largest glomerulus (G1) was located at a similar position relative to four identified landmark glomeruli, close to the entrance of the antennal nerve. This similarity in position suggests that G1s of workers, virgin queens, and males of M. scutellaris may correspond to the same glomerular entity, possibly tuned to queen-emitted volatiles since all colony members need this information. © 2015 Wiley Periodicals, Inc.

A comparative study of brain perfusion single-photon emission computed tomography and magnetic resonance imaging in patients with post-traumatic anosmia.

PubMed

Atighechi, Saeid; Salari, Hadi; Baradarantar, Mohammad Hossein; Jafari, Rozita; Karimi, Ghasem; Mirjali, Mehdi

2009-01-01

Loss of smell is a problem that can occur in up to 30% of patients with head trauma. The olfactory function investigation methods so far in use have mostly relied on subjective responses given by patients. Recently, some studies have used magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) to evaluate patients with post-traumatic anosmia. The present study seeks to detect post-traumatic anosmia and the areas in the brain that are related to olfactory impairment by using SPECT and MRI as imaging techniques. The study was conducted on 21 patients suffering from head injury and consequently anosmia as defined by an olfactory identification test. Two control groups (traumatic normosmic and nontraumatic healthy individuals) were selected. Brain MRI, qualitative and semiquantitative SPECT with 99mtc-ethyl-cysteinate-dimer were taken from all the patients. Then the brain SPECT and MRI were compared with each other. Semi-quantitative assessment of the brain perfusion SPECT revealed frontal, left parietal, and left temporal hypoperfusion as compared with the two control groups. Eighty-five percent of the anosmic patients had abnormal brain MRI. Regarding the MRI, the main abnormality proved to be in the anterior inferior region of the frontal lobes and olfactory bulbs. The findings of this study suggest that damage to the frontal lobes and olfactory bulbs as shown in the brain MRI and hypoperfusion in the frontal, left parietal, and left temporal lobes in the semiquantitative SPECT corresponds to post-traumatic anosmia. Further neurophysiological and imaging studies are definitely needed to set the idea completely.

Gene Expression Changes in the Olfactory Bulb of Mice Induced by Exposure to Diesel Exhaust Are Dependent on Animal Rearing Environment

PubMed Central

Yokota, Satoshi; Hori, Hiroshi; Umezawa, Masakazu; Kubota, Natsuko; Niki, Rikio; Yanagita, Shinya; Takeda, Ken

2013-01-01

There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m3, 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust. PMID:23940539

Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination.

PubMed

Enwere, Emeka; Shingo, Tetsuro; Gregg, Christopher; Fujikawa, Hirokazu; Ohta, Shigeki; Weiss, Samuel

2004-09-22

Previous studies demonstrating olfactory interneuron involvement in olfactory discrimination and decreased proliferation in the forebrain subventricular zone with age led us to ask whether olfactory neurogenesis and, consequently, olfactory discrimination were impaired in aged mice. Pulse labeling showed that aged mice (24 months of age) had fewer new interneurons in the olfactory bulb than did young adult (2 months of age) mice. However, the aged mice had more olfactory interneurons in total than their younger counterparts. Aged mice exhibited no differences from young adult mice in their ability to discriminate between two discrete odors but were significantly poorer at performing discriminations between similar odors (fine olfactory discrimination). Leukemia inhibitory factor receptor heterozygote mice, which have less neurogenesis and fewer olfactory interneurons than their wild-type counterparts, performed more poorly at fine olfactory discrimination than the wild types, suggesting that olfactory neurogenesis, rather than the total number of interneurons, was responsible for fine olfactory discrimination. Immunohistochemistry and Western blot analyses revealed a selective reduction in expression levels of epidermal growth factor (EGF) receptor (EGFR) signaling elements in the aged forebrain subventricular zone. Waved-1 mutant mice, which express reduced quantities of transforming growth factor-alpha, the predominant EGFR ligand in adulthood, phenocopy aged mice in olfactory neurogenesis and performance on fine olfactory discrimination tasks. These results suggest that the impairment in fine olfactory discrimination with age may result from a reduction in EGF-dependent olfactory neurogenesis.

The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

PubMed

Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S

2016-06-01

Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data. © The Author(s) 2015.

Kinetics of Satratoxin G Tissue Distribution and Excretion Following Intranasal Exposure in the Mouse

PubMed Central

Amuzie, Chidozie J.; Islam, Zahidul; Kim, Jae Kyung; Seo, Ji-Hyun; Pestka, James J.

2010-01-01

Intranasal exposure of mice to satratoxin G (SG), a macrocyclic trichothecene produced by the indoor air mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) of the nose and brain. The purpose of this study was to measure the kinetics of distribution and clearance of SG in the mouse. Following intranasal instillation of female C57B16 mice with SG (500 μg/kg bw), the toxin was detectable from 5 to 60 min in blood and plasma, with the highest concentrations, 30 and 19 ng/ml, respectively, being observed at 5 min. SG clearance from plasma was rapid and followed single-compartment kinetics (t1/2 = 20 min) and differed markedly from that of other tissues. SG concentrations were maximal at 15–30 min in nasal turbinates (480 ng/g), kidney (280 ng/g), lung (250 ng/g), spleen (200 ng/g), liver (140 ng/g), thymus (90 ng/g), heart (70 ng/g), olfactory bulb (14 ng/g), and brain (3 ng/g). The half-lives of SG in the nasal turbinate and thymus were 7.6 and 10.1 h, respectively, whereas in other organs, these ranged from 2.3 to 4.4 h. SG was detectable in feces and urine, but cumulative excretion over 5 days via these routes accounted for less than 0.3% of the total dose administered. Taken together, SG was rapidly taken up from the nose, distributed to tissues involved in respiratory, immune, and neuronal function, and subsequently cleared. However, a significant amount of the toxin was retained in the nasal turbinate, which might contribute to SG’s capacity to evoke OSN death. PMID:20466779

Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.

PubMed

Tang, Jason J; Podratz, Jewel L; Lange, Miranda; Scrable, Heidi J; Jang, Mi-Hyeon; Windebank, Anthony J

2017-07-07

Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG). Although MGF overexpression increased the overall rate of adult hippocampal neurogenesis at the proliferation stage it did not alter the distribution of neurons at post-mitotic maturation stages. We then used the lac-operon system to conditionally overexpress MGF in the mouse brain beginning at 1, 3 and 12 months with histological and behavioral observation at 24 months of age. With conditional overexpression there was an increase of BrdU+ proliferating cells and BrdU+ differentiated mature neurons in the olfactory bulbs at 24 months when overexpression was induced from 1 and 3 months of age but not when started at 12 months. This was associated with preserved olfactory function. In vitro, MGF increased the size and number of neurospheres harvested from SVZ-derived neural stem cells (NSCs). These findings indicate that MGF overexpression increases the number of neural progenitor cells and promotes neurogenesis but does not alter the distribution of adult newborn neurons at post-mitotic stages. Maintaining youthful levels of MGF may be important in reversing age-related neuronal loss and brain dysfunction.

Immunocytochemistry of the olfactory marker protein.

PubMed

Monti-Graziadei, G A; Margolis, F L; Harding, J W; Graziadei, P P

1977-12-01

The olfactory marker protein has been localized, by means of immunohistochemical techniques in the primary olfactory neurons of mice. The olfactory marker protein is not present in the staminal cells of the olfactory neuroepithelium, and the protein may be regarded as indicative of the functional stage of the neurons. Our data indicate that the olfactory marker protein is present in the synaptic terminals of the olfactory neurons at the level of the olfactory bulb glomeruli. The postsynaptic profiles of both mitral and periglomerular cells are negative.

[Posttraumatic anosmia: olfactory event related potentials and MRI evaluation].

PubMed

Liu, Jian-Feng; You, Hui; Ni, Dao-Feng; Zhang, Qiu-Hang; Yang, Da-Zhang; Wang, Na-Ya

2008-03-01

Using olfactory event related potentials (OERP) and magnetic resonance to evaluate olfactory function in patients with posttraumatic anosmia. Twenty four patients with posttraumatic anosmia were reviewed retrospectively. A thorough medical history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, brain computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Subjective olfactory testing indicated 20 of 24 patients were birhinal anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was monorhinal), except 4 cases with single nostril. Magnetic resonance imaging revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital gyrus (67%), olfactory tracts (8%) and temporal lobes (8%). OERP can objectively evaluate posttraumatic olfactory function, and magnetic resonance of olfactory pathway can precisely identify the location and extent of injures.

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus

PubMed Central

Moshkin, M. P.; Petrovski, D. V.; Akulov, A. E.; Romashchenko, A. V.; Gerlinskaya, L. A.; Ganimedov, V. L.; Muchnaya, M. I.; Sadovsky, A. S.; Koptyug, I. V.; Savelov, A. A.; Troitsky, S. Yu; Moshkn, Y. M.; Bukhtiyarov, V. I.; Kolchanov, N. A.; Sagdeev, R. Z.; Fomin, V. M.

2014-01-01

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles. PMID:25143031

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia

PubMed Central

Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Willnecker, Vivienne; Schick, Bernhard; Zizzari, Philippe; Gossage, Samuel J.; Greer, Charles A.; Leinders-Zufall, Trese; Woods, C. Geoffrey; Wood, John N.; Zufall, Frank

2013-01-01

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Nav1.7, causes a congenital inability to experience pain in humans. Here we show that Nav1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Nav1.7 in odour perception, we generated conditional null mice in which Nav1.7 was removed from all olfactory sensory neurons. In the absence of Nav1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell. PMID:21441906

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.

PubMed

Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Willnecker, Vivienne; Schick, Bernhard; Zizzari, Philippe; Gossage, Samuel J; Greer, Charles A; Leinders-Zufall, Trese; Woods, C Geoffrey; Wood, John N; Zufall, Frank

2011-04-14

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.

[Localization of NADPH-diaphorase in the brain of the shore crab Hemigrapsus sanguineus].

PubMed

Kotsiuba, E P

2005-01-01

The presence and localization of NADPH-diaphorase in the cerebral ganglion of the shore crab Hemigrapsus sanguineus was investigated with histochemical and electron histochemical methods. The reactivity of this enzyme was found in the deutrocerebrum, mainly in neuropils of olfactory lobes, the lateral antennular neuropil, a laterodorsal group of cells, and in the oculomotor nerve nucleus. Ultrastructural localization of the enzyme was detected in neurons on the perinuclear membrane, and in membranes of endoplasmic reticulum, in mitochondria and cytosol. The enzyme was found in axons of the antennular nerve, and in terminals of receptor axons in the glomerulus. The obtained data testify to participation of NO in perception and processing of the olfactory information.

Digimouse: a 3D whole body mouse atlas from CT and cryosection data

PubMed Central

Dogdas, Belma; Stout, David; Chatziioannou, Arion F; Leahy, Richard M

2010-01-01

We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html. PMID:17228106

Changes in olfactory bulb volume following lateralized olfactory training.

PubMed

Negoias, S; Pietsch, K; Hummel, T

2017-08-01

Repeated exposure to odors modifies olfactory function. Consequently, "olfactory training" plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19-43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the "Sniffin' Sticks" test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.

Flavor-Intensity Perception: Effects of Stimulus Context

PubMed Central

Marks, Lawrence E.; Shepard, Timothy G.; Burger, Kelly; Chakwin, Emily M.

2011-01-01

Stimulus context affects judgments of intensity of both gustatory and olfactory flavors, and the contextual effects are modality-specific. Does context also exert separate effects on the gustatory and olfactory components of flavor mixtures? To answer this question, in each of 4 experiments, subjects rated the perceived intensity of 16 mixtures constructed by combining 4 concentrations of the gustatory flavorant sucrose with 4 concentrations of the retronasal olfactory flavorant citral. In 1 contextual condition of each experiment, concentrations of sucrose were relatively high and those of citral low; in the other condition, the relative concentrations of sucrose and citral reversed. There were 2 main results: First, consistent with earlier findings, in 5 of the 8 conditions, the ratings were consistent with linear addition of perceived sucrose and citral; departures from additivity appeared, however, in 3 conditions where the relative concentrations of citral were high. Second, changes in context produced contrast (adaptation-like changes) in perceived intensity: The contribution to perceived intensity of a given concentration of a flavorant was smaller when the contextual concentrations of that flavorant were high rather than low. A notable exception was the absence of contextual effects on the perceived intensity of near-threshold citral. These findings suggest that the contextual effects may arise separately in the gustatory and olfactory channels, prior to the integration of perceived flavor intensity. PMID:21930139

Odorant Metabolism Analysis by an Automated Ex Vivo Headspace Gas-Chromatography Method.

PubMed

Faure, Philippe; Legendre, Arièle; Hanser, Hassan-Ismail; Andriot, Isabelle; Artur, Yves; Guichard, Elisabeth; Coureaud, Gérard; Heydel, Jean-Marie

2016-01-01

In the olfactory epithelium (OE), odorant metabolizing enzymes have the dual function of volatile component detoxification and active clearance of odorants from the perireceptor environment to respectively maintain the integrity of the tissues and the sensitivity of the detection. Although emphasized by recent studies, this enzymatic mechanism is poorly documented in mammals. Thus, olfactory metabolism has been characterized mainly in vitro and for a limited number of odorants. The automated ex vivo headspace gas-chromatography method that was developed here was validated to account for odorant olfactory metabolism. This method easily permits the measurement of the fate of an odorant in the OE environment, taking into account the odorant gaseous state and the cellular structure of the tissue, under experimental conditions close to physiological conditions and with a high reproducibility. We confirmed here our previous results showing that a high olfactory metabolizing activity of the mammary pheromone may be necessary to maintain a high level of sensitivity toward this molecule, which is critical for newborn rabbit survival. More generally, the method that is presented here may permit the screening of odorants metabolism alone or in mixture or studying the impact of aging, pathology, polymorphism or inhibitors on odorant metabolism. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

PubMed

Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

2017-11-07

Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

[Clinical and magnetic resonance imaging characteristics of isolated congenital anosmia].

PubMed

Liu, Jian-feng; Wang, Jian; You, Hui; Ni, Dao-feng; Yang, Da-zhang

2010-05-25

To report a series of patients with isolated congenital anosmia and summarize their clinical and magnetic resonance imaging (MRI) characteristics. Twenty patients with isolated congenital anosmia were reviewed retrospectively. A thorough medical and chemosensory history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, sinonasal computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Neither ENT physical examination nor nasal endoscopy was remarkable. Subjective olfactory testing indicated all of them were of anosmia. No olfactory event-related potentials to maximal stimulus were obtained. Computed tomography scan was normal. MRI revealed the absence of olfactory bulbs and tracts in all cases. And hypoplasia or aplasia of olfactory sulcus was found in all cases. All the patients had normal sex hormone level. The diagnosis of isolated congenital anosmia is established on chief complaints, physical examination, olfactory testing and olfactory imaging. MRI of olfactory pathway is indispensable.

Clinical features of olfactory disorders in patients seeking medical consultation

PubMed Central

Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

2013-01-01

Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

Time-Frequency Analysis of Chemosensory Event-Related Potentials to Characterize the Cortical Representation of Odors in Humans

PubMed Central

Huart, Caroline; Legrain, Valéry; Hummel, Thomas; Rombaux, Philippe; Mouraux, André

2012-01-01

Background The recording of olfactory and trigeminal chemosensory event-related potentials (ERPs) has been proposed as an objective and non-invasive technique to study the cortical processing of odors in humans. Until now, the responses have been characterized mainly using across-trial averaging in the time domain. Unfortunately, chemosensory ERPs, in particular, olfactory ERPs, exhibit a relatively low signal-to-noise ratio. Hence, although the technique is increasingly used in basic research as well as in clinical practice to evaluate people suffering from olfactory disorders, its current clinical relevance remains very limited. Here, we used a time-frequency analysis based on the wavelet transform to reveal EEG responses that are not strictly phase-locked to onset of the chemosensory stimulus. We hypothesized that this approach would significantly enhance the signal-to-noise ratio of the EEG responses to chemosensory stimulation because, as compared to conventional time-domain averaging, (1) it is less sensitive to temporal jitter and (2) it can reveal non phase-locked EEG responses such as event-related synchronization and desynchronization. Methodology/Principal Findings EEG responses to selective trigeminal and olfactory stimulation were recorded in 11 normosmic subjects. A Morlet wavelet was used to characterize the elicited responses in the time-frequency domain. We found that this approach markedly improved the signal-to-noise ratio of the obtained EEG responses, in particular, following olfactory stimulation. Furthermore, the approach allowed characterizing non phase-locked components that could not be identified using conventional time-domain averaging. Conclusion/Significance By providing a more robust and complete view of how odors are represented in the human brain, our approach could constitute the basis for a robust tool to study olfaction, both for basic research and clinicians. PMID:22427997

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.

PubMed

Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G; Grison, Alice; Gustincich, Stefano

2016-01-01

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

PubMed Central

Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G.; Grison, Alice; Gustincich, Stefano

2016-01-01

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain. PMID:27458372

Serotonin increases synaptic activity in olfactory bulb glomeruli

PubMed Central

Brill, Julia; Shao, Zuoyi; Puche, Adam C.; Wachowiak, Matt

2016-01-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

Serotonin increases synaptic activity in olfactory bulb glomeruli.

PubMed

Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

2016-03-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.

PubMed

Berger, W; van de Pol, D; Bächner, D; Oerlemans, F; Winkens, H; Hameister, H; Wieringa, B; Hendriks, W; Ropers, H H

1996-01-01

In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.

Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance

PubMed Central

2012-01-01

Background The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2−/− mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2−/− neurons. Results Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2−/− mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2−/− olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2−/− mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2−/− olfactory neurons. Conclusions Results presented here show that many odorant receptors are under-expressed in β3GnT2−/− mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2−/− mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2−/− mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact. PMID:22559903

Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor.

PubMed

Tillerson, Jennifer L; Caudle, W Michael; Parent, Jack M; Gong, C; Schallert, Timothy; Miller, Gary W

2006-09-15

Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.

Morphological and electrophysiological examination of olfactory sensory neurons during the early developmental prolarval stage of the sea lamprey Petromyzon marinus L

USGS Publications Warehouse

Zielinski, B.S.; Fredricks, Keith; McDonald, R.; Zaidi, A.U.

2005-01-01

This study examined olfactory sensory neuron morphology and physiological responsiveness in newly hatched sea lamprey, Petromyzon marinus L. These prolarvae hatch shortly after neural tube formation, and stay within nests for approximately 18 days, before moving downstream to silty areas where they burrow, feed and pass to the larval stage. To explore the possibility that the olfactory system is functioning during this prolarval stage, morphological and physiological development of olfactory sensory neurons was examined. The nasal cavity contained an olfactory epithelium with ciliated olfactory sensory neurons. Axons formed aggregates in the basal portion of the olfactory epithelium and spanned the narrow distance between the olfactory epithelium and the brain. The presence of asymmetric synapses with agranular vesicles within fibers in the brain, adjacent to the olfactory epithelium suggests that there was synaptic connectivity between olfactory sensory axons and the brain. Neural recordings from the surface of the olfactory epithelium showed responses following the application of L-arginine, taurocholic acid, petromyzonol sulfate (a lamprey migratory pheromone), and water conditioned by conspecifics. These results suggest that lampreys may respond to olfactory sensory input during the prolarval stage. ?? 2006 Springer Science + Business Media, LLC.

Hyposmia: an underestimated and frequent adverse effect of chemotherapy.

PubMed

Riga, Maria; Chelis, Leonidas; Papazi, Theano; Danielides, Vasilios; Katotomichelakis, Michael; Kakolyris, Stylianos

2015-10-01

Optimal function of both the olfactory sensory neurons and the olfactory mucosa is a prerequisite for normal olfactory perception. Both the olfactory neurons and mucosa might be subjects to the neurotoxic and mucotoxic effects of chemotherapy. Despite the recognized importance of olfaction in nutrition and quality of life, the potential olfactory toxicity of chemotherapy regimens has not been adequately assessed. The aim of this study is to investigate whether mucotoxic and/or neurotoxic drugs compromise olfactory performance. Forty-four consecutive patients completed the "Sniffin' Sticks" test, an objective quantitative/qualitative method to assess olfactory function, at diagnosis and immediately before the infusion of the last session of three to four chemotherapy cycles, according to the therapeutic protocol. The patients underwent therapy containing oxaliplatin and antimetabolites (5-FU or capecitabine; O+A group), taxanes and platinum analogues (cisplatin and carboplatin; T+P group), or taxanes and anthracyclines (doxorubicin or liposomal doxorubicin; T+A group). A significant decrease was noted for olfactory threshold (OT), olfactory discrimination (OD), olfactory identification (OI), and the composite threshold-discrimination-identification (TDI) score. A significant deterioration of all olfactory indices was found for each chemotherapy group. Pairwise comparisons revealed significant differences between the O+A and the T+P group regarding OT and TDI. TDI scores were significantly lower after chemotherapy in all age groups. Patients older than 50 years were found to be more susceptible to olfactory toxicity than younger patients. Patients who undergo chemotherapy experience significant compromise in their olfactory function. A grading system for olfactory toxicity is proposed.

Olfactory fingerprints for major histocompatibility complex-determined body odors.

PubMed

Schaefer, M L; Young, D A; Restrepo, D

2001-04-01

Recognition of individual body odors is analogous to human face recognition in that it provides information about identity. Individual body odors determined by differences at the major histocompatibility complex (MHC or H-2) have been shown to influence mate choice, pregnancy block, and maternal behavior in mice. Unfortunately, the mechanism and extent of the main olfactory bulb (MOB) and accessory olfactory bulb (AOB) involvement in the discrimination of animals according to H-2-type has remained ambiguous. Here we study the neuronal activation patterns evoked in the MOB in different individuals on exposure to these complex, biologically meaningful sensory stimuli. We demonstrate that body odors from H-2 disparate mice evoke overlapping but distinct maps of neuronal activation in the MOB. The spatial patterns of odor-evoked activity are sufficient to be used like fingerprints to predict H-2 identity using a novel computer algorithm. These results provide functional evidence for discrimination of H-2-determined body odors in the MOB, but do not preclude a role for the AOB. These data further our understanding of the neural strategies used to decode socially relevant odors.

Structural differences in the brain between wild and laboratory rats (Rattus norvegicus): potential contribution to wariness.

PubMed

Koizumi, Ryoko; Kiyokawa, Yasushi; Mikami, Kaori; Ishii, Akiko; Tanaka, Kazuyuki D; Tanikawa, Tsutomu; Takeuchi, Yukari

2018-05-11

Wild animals typically exhibit defensive behaviors in response to a wider range and/or a weaker intensity of stimuli compared with domestic animals. However, little is known about the neural mechanisms underlying "wariness" in wild animals. Wild rats are one of the most accessible wild animals for experimental research. Laboratory rats are a domesticated form of wild rat, belonging to the same species, and are therefore considered suitable control animals for wild rats. Based on these factors, we analyzed structural differences in the brain between wild and laboratory rats to elucidate the neural mechanisms underlying wariness. We examined wild rats trapped in Tokyo, and weight-matched laboratory rats. We then prepared brain sections and compared the basolateral complex of the amygdala (BLA), the bed nucleus of the stria terminalis (BNST), the main olfactory bulb, and the accessory olfactory bulb. The results revealed that wild rats exhibited larger BLA, BNST and caudal part of the accessory olfactory bulb compared with laboratory rats. These results suggest that the BLA, BNST, and vomeronasal system potentially contribute to wariness in wild rats.

Odor discrimination in Drosophila: from neural population codes to behavior.

PubMed

Parnas, Moshe; Lin, Andrew C; Huetteroth, Wolf; Miesenböck, Gero

2013-09-04

Taking advantage of the well-characterized olfactory system of Drosophila, we derive a simple quantitative relationship between patterns of odorant receptor activation, the resulting internal representations of odors, and odor discrimination. Second-order excitatory and inhibitory projection neurons (ePNs and iPNs) convey olfactory information to the lateral horn, a brain region implicated in innate odor-driven behaviors. We show that the distance between ePN activity patterns is the main determinant of a fly's spontaneous discrimination behavior. Manipulations that silence subsets of ePNs have graded behavioral consequences, and effect sizes are predicted by changes in ePN distances. ePN distances predict only innate, not learned, behavior because the latter engages the mushroom body, which enables differentiated responses to even very similar odors. Inhibition from iPNs, which scales with olfactory stimulus strength, enhances innate discrimination of closely related odors, by imposing a high-pass filter on transmitter release from ePN terminals that increases the distance between odor representations. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male-Male Social Interaction.

PubMed

Cansler, Hillary L; Maksimova, Marina A; Meeks, Julian P

2017-07-26

Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male-male social experience. Following the resident-intruder paradigm, Arc -expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc -expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated I H currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc -expressing interneurons. SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male-male social chemosensory encounters. We show that the plasticity-associated immediate-early gene Arc is selectively expressed in IGCs from resident males following the resident-intruder assay. After behavior, Arc -expressing IGCs are more strongly excited by sensory input stimulation and MC activation is suppressed. Arc -expressing IGCs do not show increased excitatory synaptic drive but instead show increased intrinsic excitability. These data indicate that MC-IGC plasticity is induced after male-male social chemosensory encounters, resulting in enhanced MC suppression by Arc -expressing IGCs. Copyright © 2017 the authors 0270-6474/17/377240-13$15.00/0.

Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male–Male Social Interaction

PubMed Central

Maksimova, Marina A.

2017-01-01

Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC–interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male–male social experience. Following the resident–intruder paradigm, Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IH currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident–intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc-expressing interneurons. SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male–male social chemosensory encounters. We show that the plasticity-associated immediate-early gene Arc is selectively expressed in IGCs from resident males following the resident–intruder assay. After behavior, Arc-expressing IGCs are more strongly excited by sensory input stimulation and MC activation is suppressed. Arc-expressing IGCs do not show increased excitatory synaptic drive but instead show increased intrinsic excitability. These data indicate that MC–IGC plasticity is induced after male–male social chemosensory encounters, resulting in enhanced MC suppression by Arc-expressing IGCs. PMID:28659282

Sex differences in olfactory-induced neural activation of the amygdala.

PubMed

Kikusui, Takefumi; Kajita, Mayu; Otsuka, Natsumi; Hattori, Tatsuya; Kumazawa, Kanako; Watarai, Akiyuki; Nagasawa, Miho; Inutsuka, Ayumu; Yamanaka, Akihiro; Matsuo, Naoki; Covington, Herbert E; Mogi, Kazutaka

2018-07-02

Olfactory signals, including the scent of urine, are thought to be processed by specific brain regions, such as the medial amygdala (Me), and regulate sexual behavior in a sex-dependent manner. We aimed to reveal the sex-specific neural circuit from the accessory olfactory bulb (AOB) to Me by using a transgenic mouse. We quantified the long-lasting green fluorescent protein (GFP) expression profile, which was controlled by the c-fos promotor in a sex-dependent manner by the scent of urine. Female urine predominantly activated neurons of the posterodorsal medial amygdala (MePD) in male mice and the posteroventral medial amygdala (MePV) in female mice. Male urine, in contrast, generated the opposite pattern of activation in the Me. Secondary, the selective artificial activation of these circuits was used to examine their specific behavioral function, by using a dual Cre-loxP viral infection. AAV-hSyn-FLEX-hM3Dq-EGFP-the designer receptor exclusively activated by a designer drug-was infused into the AOB after infection with trans-synaptic AAV(DJ)-CMV-mCherry-2A-Cre-TTC into either the MePD or the MePV. Double virus-transfected mice were injected with hM 3 Dq activator and their sexual behavior was monitored. However, selective activation of sex-dependent circuits, i.e., the AOB-MePD or AOB-MePV, did not significantly alter mounting or attack behavior in male mice. There were clear sex differences in the pheromone conveying circuits in the AOB-Me of mice. The sex-dependent functional activation of the Me, however, no effect on behavior. This suggests that a diverse number of nuclei and brain areas are likely to function in concert to successfully facilitate sexual and aggressive behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys

PubMed Central

Bennett, Richard S; Cress, Christina M; Ward, Jerrold M; Firestone, Cai-Yen; Murphy, Brian R; Whitehead, Stephen S

2008-01-01

Background La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys. Results Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose50 and lethal dose50 was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. Conclusion In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal. PMID:18267012

Mutation of a single residue in the S2-S3 loop of CNG channels alters the gating properties and sensitivity to inhibitors.

PubMed

Crary, J I; Dean, D M; Maroof, F; Zimmerman, A L

2000-12-01

We previously found that native cyclic nucleotide-gated (CNG) cation channels from amphibian rod cells are directly and reversibly inhibited by analogues of diacylglycerol (DAG), but little is known about the mechanism of this inhibition. We recently determined that, at saturating cGMP concentrations, DAG completely inhibits cloned bovine rod (Brod) CNG channels while only partially inhibiting cloned rat olfactory (Rolf) channels (Crary, J.I., D.M. Dean, W. Nguitragool, P.T. Kurshan, and A.L. Zimmerman. 2000. J. Gen. Phys. 116:755-768; in this issue). Here, we report that a point mutation at position 204 in the S2-S3 loop of Rolf and a mouse CNG channel (Molf) found in olfactory epithelium and heart, increased DAG sensitivity to that of the Brod channel. Mutation of this residue from the wild-type glycine to a glutamate (Molf G204E) or aspartate (Molf G204D) gave dramatic increases in DAG sensitivity without changing the apparent cGMP or cAMP affinities or efficacies. However, unlike the wild-type olfactory channels, these mutants demonstrated voltage-dependent gating with obvious activation and deactivation kinetics. Interestingly, the mutants were also more sensitive to inhibition by the local anesthetic, tetracaine. Replacement of the position 204 glycine with a tryptophan residue (Rolf G204W) not only gave voltage-dependent gating and an increased sensitivity to DAG and tetracaine, but also showed reduced apparent agonist affinity and cAMP efficacy. Sequence comparisons show that the glycine at position 204 in the S2-S3 loop is highly conserved, and our findings indicate that its alteration can have critical consequences for channel gating and inhibition.

Morphometric and ultrastructural comparison of the olfactory system in elasmobranchs: the significance of structure-function relationships based on phylogeny and ecology.

PubMed

Schluessel, Vera; Bennett, Michael B; Bleckmann, Horst; Blomberg, Simon; Collin, Shaun P

2008-11-01

This study investigated the relationship between olfactory morphology, habitat occupancy, and lifestyle in 21 elasmobranch species in a phylogenetic context. Four measures of olfactory capability, that is, the number of olfactory lamellae, the surface area of the olfactory epithelium, the mass of the olfactory bulb, and the mass of the olfactory rosette were compared between individual species and groups, comprised of species with similar habitat and/or lifestyle. Statistical analyses using generalized least squares phylogenetic regression revealed that bentho-pelagic sharks and rays possess significantly more olfactory lamellae and larger sensory epithelial surface areas than benthic species. There was no significant correlation between either olfactory bulb or rosette mass and habitat type. There was also no significant difference between the number of lamellae or the size of the sensory surface area in groups comprised of species with similar diets, that is, groups preying predominantly on crustaceans, cephalopods, echinoderms, polychaetes, molluscs, or teleosts. However, some groups had significantly larger olfactory bulb or rosette masses than others. There was little evidence to support a correlation between phylogeny and morphology, indicating that differences in olfactory capabilities are the result of functional rather than phylogenetic adaptations. All olfactory epithelia exhibited microvilli and cilia, with microvilli in both nonsensory and sensory areas, and cilia only in sensory areas. Cilia over the sensory epithelia originated from supporting cells. In contrast to teleosts, which possess ciliated and microvillous olfactory receptor types, no ciliated olfactory receptor cells were observed. This is the first comprehensive study comparing olfactory morphology to several aspects of elasmobranch ecology in a phylogenetic context.

The physiological basics of the olfactory neuro-epithelium.

PubMed

Watelet, J B; Katotomichelakis, M; Eloy, P; Danielidis, V

2009-01-01

All living organisms can detect and identify chemical substances in their environment. The olfactory epithelium is covered by a mucus layer which is essential for the function of the olfactory neurons that are directly connected to the brain through the cribriform plate. However, little is known about the composition of this mucus in humans and its significance for the diagnosis of olfactory disorders. The olfactory epithelium consists of four primary cell types, including the olfactory receptor cells essential for odour transduction. This review examines the anatomical, histological and physiological fundamentals of olfactory mucosa. Particular attention is paid to the biochemical environment of the olfactory mucosa that regulates both peri-receptor events and several protective functions.

A Closer Look at Acid-Base Olfactory Titrations

ERIC Educational Resources Information Center

Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

2005-01-01

Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

Wiring Olfaction: The Cellular and Molecular Mechanisms that Guide the Development of Synaptic Connections from the Nose to the Cortex

PubMed Central

de Castro, Fernando

2009-01-01

Within the central nervous system, the olfactory system fascinates by its developmental and physiological particularities, and is one of the most studied models to understand the mechanisms underlying the guidance of growing axons to their appropriate targets. A constellation of contact-mediated (laminins, CAMs, ephrins, etc.) and secreted mechanisms (semaphorins, slits, growth factors, etc.) are known to play different roles in the establishment of synaptic interactions between the olfactory epithelium, olfactory bulb (OB) and olfactory cortex. Specific mechanisms of this system (including the amazing family of about 1000 different olfactory receptors) have been also proposed. In the last years, different reviews have focused in partial sights, specially in the mechanisms involved in the formation of the olfactory nerve, but a detailed review of the mechanisms implicated in the development of the connections among the different olfactory structures (olfactory epithelium, OB, olfactory cortex) remains to be written. In the present work, we afford this systematic review: the different cellular and molecular mechanisms which rule the formation of the olfactory nerve, the lateral olfactory tract and the intracortical connections, as well as the few data available regarding the accessory olfactory system. These mechanisms are compared, and the implications of the differences and similarities discussed in this fundamental scenario of ontogeny. PMID:20582279

Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit.

PubMed

Hawkins, Sara J; Weiss, Lukas; Offner, Thomas; Dittrich, Katarina; Hassenklöver, Thomas; Manzini, Ivan

2017-01-01

Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB) by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks.

Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

PubMed Central

Hawkins, Sara J.; Weiss, Lukas; Offner, Thomas; Dittrich, Katarina; Hassenklöver, Thomas; Manzini, Ivan

2017-01-01

Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB) by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks. PMID:29234276

Extrabulbar olfactory system and nervus terminalis FMRFamide immunoreactive components in Xenopus laevis ontogenesis.

PubMed

Pinelli, Claudia; D'Aniello, Biagio; Polese, Gianluca; Rastogi, Rakesh K

2004-09-01

The extrabulbar olfactory system (EBOS) is a collection of nerve fibers which originate from primary olfactory receptor-like neurons and penetrate into the brain bypassing the olfactory bulbs. Our description is based upon the application of two neuronal tracers (biocytin, carbocyanine DiI) in the olfactory sac, at the cut end of the olfactory nerve and in the telencephalon of the developing clawed frog. The extrabulbar olfactory system was observed already at stage 45, which is the first developmental stage compatible with our techniques; at this stage, the extrabulbar olfactory system fibers terminated diffusely in the preoptic area. A little later in development, i.e. at stage 50, the extrabulbar olfactory system was maximally developed, extending as far caudally as the rhombencephalon. In the metamorphosing specimens, the extrabulbar olfactory system appeared reduced in extension; caudally, the fiber terminals did not extend beyond the diencephalon. While a substantial overlapping of biocytin/FMRFamide immunoreactivity was observed along the olfactory pathways as well as in the telencephalon, FMRFamide immunoreactivity was never observed to be colocalized in the same cellular or fiber components visualized by tracer molecules. The question whether the extrabulbar olfactory system and the nervus terminalis (NT) are separate anatomical entities or represent an integrated system is discussed.

In vivo Postnatal Electroporation and Time-lapse Imaging of Neuroblast Migration in Mouse Acute Brain Slices

PubMed Central

Oudin, Madeleine Julie; Doherty, Patrick; Lalli, Giovanna

2013-01-01

The subventricular zone (SVZ) is one of the main neurogenic niches in the postnatal brain. Here, neural progenitors proliferate and give rise to neuroblasts able to move along the rostral migratory stream (RMS) towards the olfactory bulb (OB). This long-distance migration is required for the subsequent maturation of newborn neurons in the OB, but the molecular mechanisms regulating this process are still unclear. Investigating the signaling pathways controlling neuroblast motility may not only help understand a fundamental step in neurogenesis, but also have therapeutic regenerative potential, given the ability of these neuroblasts to target brain sites affected by injury, stroke, or degeneration. In this manuscript we describe a detailed protocol for in vivo postnatal electroporation and subsequent time-lapse imaging of neuroblast migration in the mouse RMS. Postnatal electroporation can efficiently transfect SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS. Using confocal spinning disk time-lapse microscopy on acute brain slice cultures, neuroblast migration can be monitored in an environment closely resembling the in vivo condition. Moreover, neuroblast motility can be tracked and quantitatively analyzed. As an example, we describe how to use in vivo postnatal electroporation of a GFP-expressing plasmid to label and visualize neuroblasts migrating along the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in conditional knockout mice employing the LoxP system can also be used to target genes of interest. Pharmacological manipulation of acute brain slice cultures can be performed to investigate the role of different signaling molecules in neuroblast migration. By coupling in vivo electroporation with time-lapse imaging, we hope to understand the molecular mechanisms controlling neuroblast motility and contribute to the development of novel approaches to promote brain repair. PMID:24326479

Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse.

PubMed

Romand, Raymond; Ripp, Raymond; Poidevin, Laetitia; Boeglin, Marcel; Geffers, Lars; Dollé, Pascal; Poch, Olivier

2015-01-01

An in situ hybridization (ISH) study was performed on 2000 murine genes representing around 10% of the protein-coding genes present in the mouse genome using data generated by the EURExpress consortium. This study was carried out in 25 tissues of late gestation embryos (E14.5), with a special emphasis on the developing ear and on five distinct developing sensory organs, including the cochlea, the vestibular receptors, the sensory retina, the olfactory organ, and the vibrissae follicles. The results obtained from an analysis of more than 11,000 micrographs have been integrated in a newly developed knowledgebase, called ImAnno. In addition to managing the multilevel micrograph annotations performed by human experts, ImAnno provides public access to various integrated databases and tools. Thus, it facilitates the analysis of complex ISH gene expression patterns, as well as functional annotation and interaction of gene sets. It also provides direct links to human pathways and diseases. Hierarchical clustering of expression patterns in the 25 tissues revealed three main branches corresponding to tissues with common functions and/or embryonic origins. To illustrate the integrative power of ImAnno, we explored the expression, function and disease traits of the sensory epithelia of the five presumptive sensory organs. The study identified 623 genes (out of 2000) concomitantly expressed in the five embryonic epithelia, among which many (∼12%) were involved in human disorders. Finally, various multilevel interaction networks were characterized, highlighting differential functional enrichments of directly or indirectly interacting genes. These analyses exemplify an under-represention of "sensory" functions in the sensory gene set suggests that E14.5 is a pivotal stage between the developmental stage and the functional phase that will be fully reached only after birth.

[Clinical observation of isolated congenital anosmia].

PubMed

Li, Li; Wei, Yong-xiang; Wang, Ning-yu; Miao, Xu-tao; Yang, Ling; Ge, Xiao-hui; Wu, Ying; Liu, Jia; Tian, Jun; Li, Kun-yan; Liu, Chun-li

2013-12-01

To introduce 8 patients with isolated congenital anosmia and to discuss the clinical manifestations, imaging characteristics and family characteristics of this rarely seen disorder. Eight patients with isolated congenital anosmia treated between April 2007 and April 2012 were reviewed retrospectively. There were 4 males and 4 females. A detailed medical history collection, physical examination, nasal endoscopy, T&T and Sniffin'Sticks subjective olfactory function tests, olfactory event-related potentials sinonasal computed tomography scan and sex hormones level monitoring were performed in all patients. Seven cases underwent magnetic resonance image of olfactory pathway examination. All patients were anosmia without evidence of other defects. ENT physical examination, nasal endoscopy and computed tomography scan were normal except 4 cases with obvious nasal septum deviation, 2 cases with concha bullosa. Subjective olfactory test indicated all of them were anosmia. Olfactory event-related potentials were obtained in only 1 patient. Magnetic resonance imaging revealed the smaller or atrophy olfactory bulb and olfactory tract in five cases, the absence of olfactory bulbs and tracts in two case. A female patient did not have MRI examination because of wearing IUDs. Detection of 8 patients of sex hormones were normal. Family characteristics: 3 patients showed family inheritance pattern. The diagnosis of isolated congenital anosmia should be based on chief complaint, medical history, physical examination, olfactory test, nasal endoscopy, olfactory testing, olfactory imaging and olfactory event-related potentials. Magnetic resonance image of olfactory pathway and olfactory event-related potentials have important value for the diagnosis. More attention should be paid to the genetic susceptibility of the family.

From antenna to antenna: lateral shift of olfactory memory recall by honeybees.

PubMed

Rogers, Lesley J; Vallortigara, Giorgio

2008-06-04

Honeybees, Apis mellifera, readily learn to associate odours with sugar rewards and we show here that recall of the olfactory memory, as demonstrated by the bee extending its proboscis when presented with the trained odour, involves first the right and then the left antenna. At 1-2 hour after training using both antennae, recall is possible mainly when the bee uses its right antenna but by 6 hours after training a lateral shift has occurred and the memory can now be recalled mainly when the left antenna is in use. Long-term memory one day after training is also accessed mainly via the left antenna. This time-dependent shift from right to left antenna is also seen as side biases in responding to odour presented to the bee's left or right side. Hence, not only are the cellular events of memory formation similar in bees and vertebrate species but also the lateralized networks involved may be similar. These findings therefore seem to call for remarkable parallel evolution and suggest that the proper functioning of memory formation in a bilateral animal, either vertebrate or invertebrate, requires lateralization of processing.

No evidence for visual context-dependency of olfactory learning in Drosophila

NASA Astrophysics Data System (ADS)

Yarali, Ayse; Mayerle, Moritz; Nawroth, Christian; Gerber, Bertram

2008-08-01

How is behaviour organised across sensory modalities? Specifically, we ask concerning the fruit fly Drosophila melanogaster how visual context affects olfactory learning and recall and whether information about visual context is getting integrated into olfactory memory. We find that changing visual context between training and test does not deteriorate olfactory memory scores, suggesting that these olfactory memories can drive behaviour despite a mismatch of visual context between training and test. Rather, both the establishment and the recall of olfactory memory are generally facilitated by light. In a follow-up experiment, we find no evidence for learning about combinations of odours and visual context as predictors for reinforcement even after explicit training in a so-called biconditional discrimination task. Thus, a ‘true’ interaction between visual and olfactory modalities is not evident; instead, light seems to influence olfactory learning and recall unspecifically, for example by altering motor activity, alertness or olfactory acuity.

Individual olfactory perception reveals meaningful nonolfactory genetic information

PubMed Central

Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam

2015-01-01

Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information. PMID:26100865

[Clinical and MRI Findings in Patients with Congenital Anosmia].

PubMed

Ogawa, Takao; Kato, Tomohisa; Ono, Mayu; Shimizu, Takeshi

2015-08-01

The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 ± 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 ± 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However, diagnosis of congenital anosmia is important, as its presence can lead to dangerous situations. Careful examination for hypogonadism is also required in people with anosmia. MRI examinations of the olfactory bulbs and sulci were useful for the diagnosis of congenital anosmia.

Neuronal nitric oxide synthase in the olfactory system of an adult teleost fish Oreochromis mossambicus.

PubMed

Singru, Praful S; Sakharkar, Amul J; Subhedar, Nishikant

2003-07-11

The aim of the present study is to explore the distribution of nitric oxide synthase in the olfactory system of an adult teleost, Oreochromis mossambicus using neuronal nitric oxide synthase (nNOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry methods. Intense nNOS immunoreactivity was noticed in several olfactory receptor neurons (ORNs), in their axonal extensions over the olfactory nerve and in some basal cells of the olfactory epithelium. nNOS containing fascicles of the ORNs enter the bulb from its rostral pole, spread in the olfactory nerve layer in the periphery of the bulb and display massive innervation of the olfactory glomeruli. Unilateral ablation of the olfactory organ resulted in dramatic loss of nNOS immunoreactivity in the olfactory nerve layer of the ipsilateral bulb. In the olfactory bulb of intact fish, some granule cells showed intense immunoreactivity; dendrites arising from the granule cells could be traced to the glomerular layer. Of particular interest is the occurrence of nNOS immunoreactivity in the ganglion cells of the nervus terminalis. nNOS containing fibers were also encountered in the medial olfactory tracts as they extend to the telencephalon. The NADPHd staining generally coincides with that of nNOS suggesting that it may serve as a marker for nNOS in the olfactory system of this fish. However, mismatch was encountered in the case of mitral cells, while all are nNOS-negative, few were NADPHd positive. The present study for the first time revealed the occurrence of nNOS immunoreactivity in the ORNs of an adult vertebrate and suggests a role for nitric oxide in the transduction of odor stimuli, regeneration of olfactory epithelium and processing of olfactory signals.

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

PubMed

Chen, Ben; Zhong, Xiaomei; Mai, Naikeng; Peng, Qi; Wu, Zhangying; Ouyang, Cong; Zhang, Weiru; Liang, Wanyuan; Wu, Yujie; Liu, Sha; Chen, Lijian; Ning, Yuping

2018-03-15

Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.

Transcriptome analysis in different developmental stages of Batocera horsfieldi (Coleoptera: Cerambycidae) and comparison of candidate olfactory genes

PubMed Central

Yang, Wei; Yang, Chunping; Zhang, Jin; Yang, Yang; Wang, Baoxin; Guan, Fengrong

2018-01-01

The white-striped longhorn beetle Batocera horsfieldi (Coleoptera: Cerambycidae) is a polyphagous wood-boring pest that causes substantial damage to the lumber industry. Moreover olfactory proteins are crucial components to function in related processes, but the B. horsfieldi genome is not readily available for olfactory proteins analysis. In the present study, developmental transcriptomes of larvae from the first instar to the prepupal stage, pupae, and adults (females and males) from emergence to mating were built by RNA sequencing to establish a genetic background that may help understand olfactory genes. Approximately 199 million clean reads were obtained and assembled into 171,664 transcripts, which were classified into 23,380, 26,511, 22,393, 30,270, and 87, 732 unigenes for larvae, pupae, females, males, and combined datasets, respectively. The unigenes were annotated against NCBI’s non-redundant nucleotide and protein sequences, Swiss-Prot, Gene Ontology (GO), Pfam, Clusters of Eukaryotic Orthologous Groups (KOG), and KEGG Orthology (KO) databases. A total of 43,197 unigenes were annotated into 55 sub-categories under the three main GO categories; 25,237 unigenes were classified into 26 functional KOG categories, and 25,814 unigenes were classified into five functional KEGG Pathway categories. RSEM software identified 2,983, 3,097, 870, 2,437, 5,161, and 2,882 genes that were differentially expressed between larvae and males, larvae and pupae, larvae and females, males and females, males and pupae, and females and pupae, respectively. Among them, genes encoding seven candidate odorant binding proteins (OBPs) and three chemosensory proteins (CSPs) were identified. RT-PCR and RT-qPCR analyses showed that BhorOBP3, BhorCSP2, and BhorOBPC1/C3/C4 were highly expressed in the antenna of males, indicating these genes may may play key roles in foraging and host-orientation in B. horsfieldi. Our results provide valuable molecular information about the olfactory system in B. horsfieldi and will help guide future functional studies on olfactory genes. PMID:29474419

Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis.

PubMed

Apter, A J; Gent, J F; Frank, M E

1999-09-01

To characterize the relationship between allergic rhinitis, the severity and duration of nasal disease, olfactory function, and self-reported olfactory symptoms, including fluctuations or distortions in odor perception. Assessment of olfactory function and symptoms of 90 patients with allergic rhinitis. A clinic of a university teaching hospital and research facility. Sixty patients who presented to the Taste and Smell Clinic who had positive allergy test results and 30 patients who presented to the Allergy-Immunology Clinic. The Taste and Smell Clinic patients were grouped by nasal-sinus disease status (30 without chronic rhinosinusitis or nasal polyps, 14 with chronic rhinosinusitis but without polyps, and 16 with nasal polyps). Subjective olfactory symptom questionnaire and objective olfactory function tests. The Allergy-Immunology Clinic patients were diagnosed as being normosmic and the Taste and Smell Clinic patients as being hyposmic or anosmic with olfactory loss that increased significantly with nasal-sinus disease severity. Comparisons with normative data confirm that olfactory scores observed in all groups were significantly lower than expected because of the aging process alone. The self-reported duration of olfactory loss increased significantly with nasal-sinus disease severity. The Taste and Smell Clinic patients without chronic rhinosinusitis or nasal polyps reported the greatest incidence of olfactory distortions and olfactory loss associated with upper respiratory tract infections. There appears to be a continuum of duration and severity of olfactory loss in allergic rhinitis that parallels increasing severity of nasal-sinus disease. As a result of the increased frequency of respiratory infection associated with allergic rhinitis, these patients are at risk for damage to the olfactory epithelium.

Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

PubMed

Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

2010-08-01

Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome

PubMed Central

Layman, W.S.; McEwen, D.P.; Beyer, L.A.; Lalani, S.R.; Fernbach, S.D.; Oh, E.; Swaroop, A.; Hegg, C.C.; Raphael, Y.; Martens, J.R.; Martin, D.M.

2009-01-01

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7Gt/+ olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development. PMID:19279158

Parallel Olfactory Processing in the Honey Bee Brain: Odor Learning and Generalization under Selective Lesion of a Projection Neuron Tract

PubMed Central

Carcaud, Julie; Giurfa, Martin; Sandoz, Jean Christophe

2016-01-01

The function of parallel neural processing is a fundamental problem in Neuroscience, as it is found across sensory modalities and evolutionary lineages, from insects to humans. Recently, parallel processing has attracted increased attention in the olfactory domain, with the demonstration in both insects and mammals that different populations of second-order neurons encode and/or process odorant information differently. Among insects, Hymenoptera present a striking olfactory system with a clear neural dichotomy from the periphery to higher-order centers, based on two main tracts of second-order (projection) neurons: the medial and lateral antennal lobe tracts (m-ALT and l-ALT). To unravel the functional role of these two pathways, we combined specific lesions of the m-ALT tract with behavioral experiments, using the classical conditioning of the proboscis extension response (PER conditioning). Lesioned and intact bees had to learn to associate an odorant (1-nonanol) with sucrose. Then the bees were subjected to a generalization procedure with a range of odorants differing in terms of their carbon chain length or functional group. We show that m-ALT lesion strongly affects acquisition of an odor-sucrose association. However, lesioned bees that still learned the association showed a normal gradient of decreasing generalization responses to increasingly dissimilar odorants. Generalization responses could be predicted to some extent by in vivo calcium imaging recordings of l-ALT neurons. The m-ALT pathway therefore seems necessary for normal classical olfactory conditioning performance. PMID:26834589

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes.

PubMed

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong

2018-05-01

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.

Proteomic Analysis of the Human Olfactory Bulb.

PubMed

Dammalli, Manjunath; Dey, Gourav; Madugundu, Anil K; Kumar, Manish; Rodrigues, Benvil; Gowda, Harsha; Siddaiah, Bychapur Gowrishankar; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, Thottethodi Subrahmanya Keshava

2017-08-01

The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death. In this context, the olfactory bulb is a vital component of the olfactory system receiving sensory information from the axons of the olfactory receptor neurons located in the nasal cavity and the first place that processes the olfactory information. We report in this study original observations on the human olfactory bulb proteome in healthy subjects, using a high-resolution mass spectrometry-based proteomic approach. We identified 7750 nonredundant proteins from human olfactory bulbs. Bioinformatics analysis of these proteins showed their involvement in biological processes associated with signal transduction, metabolism, transport, and olfaction. These new observations provide a crucial baseline molecular profile of the human olfactory bulb proteome, and should assist the future discovery of biomarker proteins and novel diagnostics associated with diseases characterized by olfactory dysfunction.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

2013-01-15

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidativemore » stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The olfactory antioxidant response is blocked by Nrf2 knockdown. ► Disruption of olfactory neurobehaviors is associated with Nrf2 knockdown. ► Nrf2 morphants show increased cell death and olfactory sensory neuron loss.« less

Comparative modular analysis of gene expression in vertebrate organs.

PubMed

Piasecka, Barbara; Kutalik, Zoltán; Roux, Julien; Bergmann, Sven; Robinson-Rechavi, Marc

2012-03-29

The degree of conservation of gene expression between homologous organs largely remains an open question. Several recent studies reported some evidence in favor of such conservation. Most studies compute organs' similarity across all orthologous genes, whereas the expression level of many genes are not informative about organ specificity. Here, we use a modularization algorithm to overcome this limitation through the identification of inter-species co-modules of organs and genes. We identify such co-modules using mouse and human microarray expression data. They are functionally coherent both in terms of genes and of organs from both organisms. We show that a large proportion of genes belonging to the same co-module are orthologous between mouse and human. Moreover, their zebrafish orthologs also tend to be expressed in the corresponding homologous organs. Notable exceptions to the general pattern of conservation are the testis and the olfactory bulb. Interestingly, some co-modules consist of single organs, while others combine several functionally related organs. For instance, amygdala, cerebral cortex, hypothalamus and spinal cord form a clearly discernible unit of expression, both in mouse and human. Our study provides a new framework for comparative analysis which will be applicable also to other sets of large-scale phenotypic data collected across different species.

The Embryonic Septum and Ventral Pallium, New Sources of Olfactory Cortex Cells

PubMed Central

de Carlos, Juan A.

2012-01-01

The mammalian olfactory cortex is a complex structure located along the rostro-caudal extension of the ventrolateral prosencephalon, which is divided into several anatomically and functionally distinct areas: the anterior olfactory nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and the more caudal entorhinal cortex. Multiple forebrain progenitor domains contribute to the cellular diversity of the olfactory cortex, which is invaded simultaneously by cells originating in distinct germinal areas in the dorsal and ventral forebrain. Using a combination of dye labeling techniques, we identified two novel areas that contribute cells to the developing olfactory cortices, the septum and the ventral pallium, from which cells migrate along a radial and then a tangential path. We characterized these cell populations by comparing their expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory cell populations. PMID:22984546

Morphology of the olfactory system in the predatory mite Phytoseiulus persimilis.

PubMed

van Wijk, Michiel; Wadman, Wytse J; Sabelis, Maurice W

2006-01-01

The predatory mite Phytoseiulus persimilis locates its prey, the two-spotted spider mite, by means of herbivore-induced plant volatiles. The olfactory response to this quantitatively and qualitatively variable source of information is particularly well documented. The mites perform this task with a peripheral olfactory system that consists of just five putative olfactory sensilla that reside in a dorsal field at the tip of their first pair of legs. The receptor cells innervate a glomerular olfactory lobe just ventral of the first pedal ganglion. We have made a 3D reconstruction of the caudal half of the olfactory lobe in adult females. The glomerular organization as well as the glomerular innervation appears conserved across different individuals. The adult females have, by approximation, a 1:1 ratio of olfactory receptor cells to olfactory glomeruli.

Olfactory memory in the old and very old: relations to episodic and semantic memory and APOE genotype.

PubMed

Larsson, Maria; Hedner, Margareta; Papenberg, Goran; Seubert, Janina; Bäckman, Lars; Laukka, Erika J

2016-02-01

The neuroanatomical organization that underlies olfactory memory is different from that of other memory types. The present work examines olfactory memory in an elderly population-based sample (Swedish National Study on Aging and Care in Kungsholmen) aged 60-100 years (n = 2280). We used structural equation modeling to investigate whether olfactory memory in old age is best conceptualized as a distinct category, differentiated from episodic and semantic memory. Further, potential olfactory dedifferentiation and genetic associations (APOE) to olfactory function in late senescence were investigated. Results are in support of a 3-factor solution where olfactory memory, as indexed by episodic odor recognition and odor identification, is modeled separately from episodic and semantic memory for visual and verbal information. Increasing age was associated with poorer olfactory memory performance, and observed age-related deficits were further exacerbated for carriers of the APOE ε4 allele; these effects tended to be larger for olfactory memory compared to episodic and semantic memory pertaining to other sensory systems (vision, auditory). Finally, stronger correlations between olfactory and episodic memory, indicating dedifferentiation, were observed in the older age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

[How we smell and what it means to us: basic principles of the sense of smell].

PubMed

Manzini, I; Frasnelli, J; Croy, I

2014-12-01

The origins of the sense of smell lie in the perception of environmental molecules and go back to unicellular organisms such as bacteria. Odors transmit a multitude of information about the chemical composition of our environment. The sense of smell helps people and animals with orientation in space, warns of potential threats, influences the choice of sexual partners, regulates food intake and influences feelings and social behavior in general. The perception of odors begins in sensory neurons residing in the olfactory epithelium that express G protein-coupled receptors, the so-called olfactory receptors. The binding of odor molecules to olfactory receptors initiates a signal transduction cascade that converts olfactory stimuli into electrical signals. These signals are then transmitted to the olfactory bulb, the first relay center in the olfactory pathway, via the axons of the sensory neurons. The olfactory information is processed in the bulb and then transferred to higher olfactory centers via axons of mitral cells, the bulbar projection neurons. This review describes the mechanisms involved in peripheral detection of odorants, outlines the further processing of olfactory information in higher olfactory centers and finally gives an overview of the overall significance of the ability to smell.

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

PubMed

Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Olfaction in the autism spectrum.

PubMed

Galle, Sara A; Courchesne, Valérie; Mottron, Laurent; Frasnelli, Johannes

2013-01-01

The autism spectrum (AS) is characterised by enhanced perception in vision and audition, described by the enhanced perceptual functioning (EPF) model. This model predicts enhanced low-level (discrimination of psychophysical dimensions), and mid- and high-level (pattern detection and identification) perception. The EPF model is here tested for olfaction by investigating olfactory function in autistic and Asperger participants. Experiment 1 targeted higher-order olfactory processing by assessing olfactory identification in nine Asperger, ten autistic, and eleven typically developed individuals. Experiment 2 focused on low-level olfactory processing; we assessed odour detection thresholds and odour discrimination in five Asperger, five autistic, and five typically developed males. Olfactory identification was impaired in autistic participants relative to control and Asperger participants. Typical performance in low-level olfactory processing suggests that neural mechanisms involved in the perceptual phenotype of AS do not affect structures implicated in olfactory processing. Reduced olfactory identification is limited to autistic participants who displayed speech delay and may be due to a reduced facility to use verbal labels. The apparent absence of enhanced olfactory perception of AS participants distinguishes the olfactory system from the other sensory modalities and might be caused by the absence of an obligatory thalamic relay.

Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

PubMed Central

Polese, Gianluca; Bertapelle, Carla

2016-01-01

ABSTRACT The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens. PMID:27069253

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

PubMed Central

Liang, Yajie; Li, Kaizhen; Riecken, Kristoffer; Maslyukov, Anatoliy; Gomez-Nicola, Diego; Kovalchuk, Yury; Fehse, Boris; Garaschuk, Olga

2016-01-01

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. PMID:27174051

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

PubMed

Moshkin, M P; Petrovski, D V; Akulov, A E; Romashchenko, A V; Gerlinskaya, L A; Ganimedov, V L; Muchnaya, M I; Sadovsky, A S; Koptyug, I V; Savelov, A A; Troitsky, S Yu; Moshkn, Y M; Bukhtiyarov, V I; Kolchanov, N A; Sagdeev, R Z; Fomin, V M

2014-10-07

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The role of olfaction throughout juvenile development: functional adaptations in elasmobranchs.

PubMed

Schluessel, Vera; Bennett, Michael B; Bleckmann, Horst; Collin, Shaun P

2010-04-01

Seven elasmobranch species, a group known for their highly-developed sense of smell, were examined for developmental changes in the number of olfactory lamellae, the size of the surface area of the sensory olfactory epithelium and the mass of both the olfactory rosettes (primary input to the CNS), and the olfactory bulbs. Within each species, juveniles possessed miniature versions of the adult olfactory organs, visually not distinguishable from these and without any obvious structural differences (e.g., with respect to the number of lamellae and the extent of secondary folding) between differently sized individuals. The size of the olfactory organs was positively correlated with body length and body mass, although few species showed proportional size scaling. In Aetobatus narinari and Aptychotrema rostrata, olfactory structures increased in proportion to body size. With respect to the growth of the olfactory bulb, all species showed allometric but not proportional growth. Olfaction may be of particular importance to juveniles in general, which are often subjected to heavy predation rates and fierce inter/intraspecific competition. Accordingly, it would be advantageous to possess a fully functional olfactory system early on in development. Slow growth rates of olfactory structures could then be attributed to a greater reliance on other sensory systems with increasing age or simply be regarded as maintaining an already optimized olfactory system. (c) 2009 Wiley-Liss, Inc.

Olfactory acuity in theropods: palaeobiological and evolutionary implications.

PubMed

Zelenitsky, Darla K; Therrien, François; Kobayashi, Yoshitsugu

2009-02-22

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.

Olfactory acuity in theropods: palaeobiological and evolutionary implications

PubMed Central

Zelenitsky, Darla K.; Therrien, François; Kobayashi, Yoshitsugu

2008-01-01

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds. PMID:18957367

Olfactory receptor neuron profiling using sandalwood odorants.

PubMed

Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

2004-07-01

The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

Relationship between uninasal anatomy and uninasal olfactory ability.

PubMed

Hornung, D E; Leopold, D A

1999-01-01

To examine the relationship between uninasal anatomy and olfactory ability. A stepwise analysis of variance was used to regress the logarithm of the percentage of correct responses on the Odorant Confusion Matrix (a measure of olfactory ability) against the logarithm of nasal volume measurements determined from computed tomographic scans. Nineteen patients with hyposmia whose olfactory losses were thought to be related to conductive disorders. After correcting for sex differences, a mathematical model was developed in which the volume of 6 regions of the nasal cavity, 6 first-order interactions, and 3 second-order interactions accounted for 97% of the variation in the measure of olfactory ability. Increases in the size of compartments of the nasal cavity around the olfactory cleft generally increase olfactory ability. Also, anatomical differences in the nasal cavities of men and women may account, in part, for sex differences in olfactory ability.

Modern psychophysical tests to assess olfactory function.

PubMed

Eibenstein, A; Fioretti, A B; Lena, C; Rosati, N; Amabile, G; Fusetti, M

2005-07-01

The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.

Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

PubMed

Strowbridge, Ben W

2010-02-11

In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks. Copyright 2010 Elsevier Inc. All rights reserved.

Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

ERIC Educational Resources Information Center

Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

2004-01-01

Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

PubMed Central

Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

2015-01-01

Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

The Prevalence of Olfactory Dysfunction in Chronic Rhinosinusitis

PubMed Central

Kohli, Preeti; Naik, Akash N.; Harruff, E. Emily; Nguyen, Shaun A.; Schlosser, Rodney J.; Soler, Zachary M.

2016-01-01

Objective Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study are to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. Data Sources A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Review Methods Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. Results A total of 47 articles were included in systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin’ Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96±7.11 using the 40-item Smell Identification Test, 8.60±2.81 using the Brief Smell Identification Test, 21.96±8.88 using total Sniffin’ sticks score, 5.65±1.51 using Sniffin’ Sticks threshold, 9.21±4.63 using Sniffin’ Sticks discrimination, 9.47±3.92 using Sniffin’ Sticks Identification, and 8.90±5.14 using the questionnaire for olfactory disorders-negative statements. Conclusion In chronic rhinosinusitis populations, a significant percentage of patients experience olfactory dysfunction and mean olfactory scores are within the dysosmic range. PMID:27873345

Effects of 20 mg oral Δ9-tetrahydrocannabinol on the olfactory function of healthy volunteers*

PubMed Central

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-01-01

Aims Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ9-tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. Methods The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Results Δ9-Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, −7.8 to −2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Conclusions Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. PMID:24802974

Effects of 20 mg oral Δ(9) -tetrahydrocannabinol on the olfactory function of healthy volunteers.

PubMed

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-11-01

Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Δ(9) -Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, -7.8 to -2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. © 2014 The British Pharmacological Society.

Single olfactory organ associated with prosencephalic malformation and cyclopia in a Xenopus laevis tadpole.

PubMed

Magrassi, L; Graziadei, P P

1987-06-02

A cyclops Xenopus laevis tadpole with a single olfactory organ is described. At a stage comparable to 48, the telencephalon was severely atrophic and only the region where the olfactory fibres terminated appeared to have the cytoarchitecture of the olfactory bulb. In this animal the central nervous system (CNS) appeared normally developed only posterior to the preoptic area. The hypothesis of a diencephalic origin of the region where the olfactory fibres terminated is discussed in the light of our previous results of olfactory placode transplantation. By analogy between this case and other malformations (cyclopia, holoprosencephaly) in higher vertebrates and humans, the need is emphasized for a more precise anatomical description of the olfactory input in related malformations.

Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.

PubMed

Bett, N N; Hinch, S G; Kaukinen, K H; Li, S; Miller, K M

2018-04-16

Expression of 12 olfactory genes was analysed in adult sockeye salmon Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from their natal migration route. Variation was found in six of these genes, all of which were olfc olfactory receptors and had lower expression levels in salmon nearing spawning grounds. The results may reflect decreased sensitivity to natal water olfactory cues as these fish are no longer seeking the correct migratory route. The expression of olfactory genes during the olfactory-mediated spawning migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these findings demonstrate a link between migratory behaviours and olfactory plasticity that provides a basis for future molecular research on salmon homing. © 2018 The Fisheries Society of the British Isles.

Integration of Multidisciplinary Sensory Data:

PubMed Central

Miller, Perry L.; Nadkarni, Prakash; Singer, Michael; Marenco, Luis; Hines, Michael; Shepherd, Gordon

2001-01-01

The paper provides an overview of neuroinformatics research at Yale University being performed as part of the national Human Brain Project. This research is exploring the integration of multidisciplinary sensory data, using the olfactory system as a model domain. The neuroinformatics activities fall into three main areas: 1) building databases and related tools that support experimental olfactory research at Yale and can also serve as resources for the field as a whole, 2) using computer models (molecular models and neuronal models) to help understand data being collected experimentally and to help guide further laboratory experiments, 3) performing basic neuroinformatics research to develop new informatics technologies, including a flexible data model (EAV/CR, entity-attribute-value with classes and relationships) designed to facilitate the integration of diverse heterogeneous data within a single unifying framework. PMID:11141511

Olfactory epithelium changes in germfree mice

PubMed Central

François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

2016-01-01

Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status.

PubMed

Nakahara, Thiago S; Cardozo, Leonardo M; Ibarra-Soria, Ximena; Bard, Andrew D; Carvalho, Vinicius M A; Trintinalia, Guilherme Z; Logan, Darren W; Papes, Fabio

2016-02-15

Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors. Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed. Our results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup-oriented behaviors in mice.

Parallel odor processing by mitral and middle tufted cells in the olfactory bulb.

PubMed

Cavarretta, Francesco; Burton, Shawn D; Igarashi, Kei M; Shepherd, Gordon M; Hines, Michael L; Migliore, Michele

2018-05-16

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations. We have analyzed the functional roles of these pathways by using a morphologically and physiologically realistic three-dimensional model to explore the MC and mTC microcircuits in the glomerular layer and deeper plexiform layer. The model makes several predictions. MCs and mTCs are controlled by similar computations in the glomerular layer but are differentially modulated in deeper layers. The intrinsic properties of mTCs promote their synchronization through a common granule cell input. Finally, the MC and mTC pathways can be coordinated through the deep short-axon cells in providing input to the olfactory cortex. The results suggest how these mechanisms can dynamically select the functional network connectivity to create the overall output of the OB and promote the dynamic synchronization of glomerular units for any given odor stimulus.

Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

PubMed

Sakamoto, Kazuhiro; Matsumura, Shigenobu; Okafuji, Yoko; Eguchi, Ai; Lee, Shinhye; Adachi, Shin-ichi; Fujitani, Mina; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

2015-01-01

High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

Mesopredator behavioral response to olfactory signals of an apex predator.

PubMed

Wikenros, Camilla; Jarnemo, Anders; Frisén, Marielle; Kuijper, Dries P J; Schmidt, Krzysztof

2017-01-01

Olfactory signals constitute an important mechanism in interspecific interactions, but little is known regarding their role in communication between predator species. We analyzed the behavioral responses of a mesopredator, the red fox ( Vulpes vulpes ), to an olfactory cue (scat) of an apex predator, the lynx ( Lynx lynx ) in Białowieża Primeval Forest, Poland, using video camera traps. Red fox visited sites with scats more often than expected and the duration of their visits was longer at scat sites than at control sites (no scat added). Vigilant behavior, sniffing and scent marking (including over-marking) occurred more often at scat sites compared to control sites, where foxes mainly passed by. Vigilance was most pronounced during the first days of the recordings. Red fox behavior was also influenced by foxes previously visiting scat sites. They sniffed and scent marked (multiple over-marking) more frequently when the lynx scat had been over-marked previously by red fox. Fox visits to lynx scats may be seen as a trade-off between obtaining information on a potential food source (prey killed by lynx) and the potential risk of predation by an apex predator.

[The sense of smell in daily life].

PubMed

Steinbach, S; Hundt, W; Zahnert, T

2008-09-01

An intact olfactory system affects all areas of life including the creation of new life, partner selection, daily hygiene, food intake, and the perception of danger from gas and smoke. The olfactory system is most effective from adolescence to middle age. With advancing age the regeneration of olfactory receptor cells decreases, often resulting in an increasing loss of smell. Functional anosmia affects 5% of the general population and 10% of those over 65. Therefore, olfactory dysfunctions are not uncommon. The following provides an overview of the physiology of smell, olfactory testing, special olfactory dysfunctions as well as treatment and general recommendations.

Ulex europaeus I and glycine max bind to the human olfactory bulb.

PubMed

Nagao, M; Oka, N; Kamo, H; Akiguchi, I; Kimura, J

1993-12-24

The distribution of binding sites for the fucose-selective lectin Ulex europaeus I and the terminal N-acetylgalactosamine-selective lectin glycine max in the human olfactory bulb were studied. These lectins bound to primary olfactory axons in the olfactory nerve layer and the glomerular layer. They also bound to fibers located in the deeper layers such as the external plexiform layer and the granular layer. Furthermore they projected to the olfactory stalk but not in the cerebrum. The deeper projections of the lectin binding fibers may affect the function of the olfactory bulb in humans.

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia

PubMed Central

Roberts, Rosebud O.; Christianson, Teresa J. H.; Kremers, Walter K.; Mielke, Michelle M.; Machulda, Mary M.; Vassilaki, Maria; Alhurani, Rabe E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

2015-01-01

IMPORTANCE To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD), markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE To examine associations of impaired olfaction with incident MCI subtypes, and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging were clinically evaluated at baseline and every 15-months thereafter, and classified as having normal cognition, MCI (amnestic, aMCI and nonamnestic, naMCI), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES Mild cognitive impairment, AD dementia, longitudinal change in cognitive performance measures. RESULTS Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by decrease in number of correct responses in B-SIT score, and an increased risk of aMCI. Compared to the upper B-SIT quartile (Q4, best scores), hazard ratios (HR) were 1.12; P = 0.68 for Q3; HR, 1.95; P =0.003 for Q2; and HR, 2.18; P = 0.001 (worst scores; p for trend <0.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD, with a significant dose-response with worsening B-SIT quartiles. Compared to Q4, HR estimates were 3.02, P = 0.038 for Q3; HR, 3.63; P = 0.024 for Q2; and HR, 5.20; P = 0.001 for Q1. After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10; p < 0.001), and improved the model concordance. CONCLUSIONS AND RELEVANCE Olfactory impairment predicts incident aMCI and progression from aMCI to AD. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life, and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress. PMID:26569387

Distribution of Cytoglobin in the Mouse Brain

PubMed Central

Reuss, Stefan; Wystub, Sylvia; Disque-Kaiser, Ursula; Hankeln, Thomas; Burmester, Thorsten

2016-01-01

Cytoglobin (Cygb) is a vertebrate globin with so far poorly defined function. It is expressed in the fibroblast cell-lineage but has also been found in neurons. Here we provide, using immunohistochemistry, a detailed study on the distribution of Cygb in the mouse brain. While Cygb is a cytoplasmic protein in active cells of the supportive tissue, in neurons it is located in the cytoplasm and the nucleus. We found the expression of Cygb in all brain regions, although only a fraction of the neurons was Cygb-positive. Signals were of different intensity ranging from faint to very intense. Telencephalic neurons in all laminae of the cerebral cortex (CCo), in the olfactory bulb (in particular periglomerular cells), in the hippocampal formation (strongly stained pyramidal cells with long processes), basal ganglia (scattered multipolar neurons in the dorsal striatum, dorsal and ventral pallidum (VP)), and in the amygdala (neurons with unlabeled processes) were labeled by the antibody. In the diencephalon, we observed Cygb-positive neurons of moderate intensity in various nuclei of the dorsal thalamus, in the hypothalamus, metathalamus (geniculate nuclei), epithalamus with strong labeling of habenular nucleus neurons and no labeling of pineal cells, and in the ventral thalamus. Tegmental neurons stood out by strongly stained somata with long processes in, e.g., the laterodorsal nucleus. In the tectum, faintly labeled neurons and fibers were detected in the superior colliculus (SC). The cerebellum exhibited unlabeled Purkinje-neurons but signs of strong afferent cortical innervation. Neurons in the gray matter of the spinal cord showed moderate immunofluorescence. Peripheral ganglia were not labeled by the antibody. The Meynert-fascicle and the olfactory and optic nerves/tracts were the only Cygb-immunoreactive (Cygb-IR) fiber systems. Notably, we found a remarkable level of colocalization of Cygb and neuronal nitric oxide (NO)-synthase in neurons, which supports a functional association. PMID:27199679

Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lever, J.R.; Hartig, P.R.; Wong, D.F.

1985-05-01

2-(/sup 125/1)-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-(/sup 123/1)-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-(/sup 125/1)-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2more » antagonist, inhibited binding. 2-(/sup 123/1)-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-((/sup 11/C)-Me)-2-Br-LSD (/sup 11/C-MBL) from (/sup 11/C)-methyl iodide and 2-Br-LSD for PET imaging trials. /sup 11/C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-(/sup 125/1)-LSD. After 30 minutes, peak tissue to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited /sup 11/C-MBL binding. /sup 11/C-MBL is a promising candidate for PET studies of S2 receptors.« less

Morphology and physiology of the olfactory system of blood-feeding insects.

PubMed

Guidobaldi, F; May-Concha, I J; Guerenstein, P G

2014-01-01

Several blood-feeding (hematophagous) insects are vectors of a number of diseases including dengue, Chagas disease and leishmaniasis which persistently affect public health throughout Latin America. The vectors of those diseases include mosquitoes, triatomine bugs and sandflies. As vector control is an efficient way to prevent these illnesses it is important to understand the sensory biology of those harmful insects. We study the physiology of the olfactory system of those insects and apply that knowledge on the development of methods to manipulate their behavior. Here we review some of the latest information on insect olfaction with emphasis on hematophagous insects. The insect olfactory sensory neurons are housed inside hair-like organs called sensilla which are mainly distributed on the antenna and mouthparts. The identity of many of the odor compounds that those neurons detect are already known in hematophagous insects. They include several constituents of host (vertebrate) odor, sex, aggregation and alarm pheromones, and compounds related to egg-deposition behavior. Recent work has contributed significant knowledge on how odor information is processed in the insect first odor-processing center in the brain, the antennal lobe. The quality, quantity, and temporal features of the odor stimuli are encoded by the neural networks of the antennal lobe. Information regarding odor mixtures is also encoded. While natural mixtures evoke strong responses, synthetic mixtures that deviate from their natural counterparts in terms of key constituents or proportions of those constituents evoke weaker responses. The processing of olfactory information is largely unexplored in hematophagous insects. However, many aspects of their olfactory behavior are known. As in other insects, responses to relevant single odor compounds are weak while natural mixtures evoke strong responses. Future challenges include studying how information about odor mixtures is processed in their brain. This could help develop highly attractive synthetic odor blends to lure them into traps. Copyright © 2014 Elsevier Ltd. All rights reserved.

Osmophobia and olfactory functions in patients with migraine.

PubMed

Kayabaşoglu, Gürkan; Altundag, Aytug; Kotan, Dilcan; Dizdar, Denizhan; Kaymaz, Recep

2017-02-01

Olfactory dysfunction and migraine has been associated for a long time. In this study, we planned to compare olfactory functions in patients with migraine and osmophobia with patients having migraine but no osmophobia, in addition with a normal control group using "Sniffin' Sticks" test. The main distinction of this study is that all qualitative and quantitative properties of olfactory functions; threshold, discrimination and identification, are evaluated separately and jointly. Thirty healthy person aged between 16 and 56 (18 women, 12 men) and 60 migraine patients aged between 15 and 54 (39 women, 21 man) were included in the study. All patients have been inquired about osmophobia and have been assessed with Hedonic tone assessment. Osmophobia has been tested for perfume, cigarette smoke, leather, stale food, soy sauce, fish, spices and coffee smells. Olfactory functions has been assessed with "Sniffin' Sticks" smell test. Thresholds, discrimination and identification have been determined for each patient. In migraine patients with osmophobia, threshold was 7.75 ± 2.3, in migraine patients without osmophobia threshold was 8.25 ± 1.5 and threshold was 10.75 ± 1.3 for the control group. Discrimination score was 6 ± 1.2 in migraine patients with osmophobia, 9 ± 0.8 in patients without osmophobia and was 12 ± 1.4 in the control group. In migraine patient with or without osmophobia Threshold/Discrimination/Identification (TDI) scores were lower than the control group. The most important parameter in our study is that discrimination scores were especially lower in patients with osmophobia. We believe that this decrease in discrimination in migraine patients with osmophobia; who claim that they smell everything and they are sensitive to all smells, is significant. Further studies about smell discrimination will help better understand some conditions; especially anosmia and hyposmia after upper respiratory tract infections and parosmia.

Impact of endoscopic sinus surgery on olfaction and use of alternative components in odor threshold measurement.

PubMed

Gupta, Divya; Gulati, Achal; Singh, Ishwar; Tekur, Uma

2015-01-01

One of the major causes of olfactory disturbances is chronic rhinosinusitis (CRS), and the main surgical modality to treat CRS is functional endoscopic sinus surgery (FESS). It, therefore, is essential to assess the effect of this surgery on olfaction. Also, it is necessary to find new ways of measuring olfaction so as to reduce dependability on standard tests available. To study the prevalence of olfactory impairment in patients with CRS and to evaluate the impact of FESS on olfaction. The study also aims at investigating the use of other odorants in place of butanol-1 in the Connecticut Chemosensory Clinical Research Center test. Forty patients of CRS without nasal polyposis were included in the study to analyze the prevalence of olfactory dysfunction and examine the influence of FESS at 1 and 3 months after surgery. Computed tomography scores (Lund Mackay scores) were calculated preoperatively, whereas other tests, viz., visual analog scale scoring, nasal endoscopy (Lund Kennedy scoring), and composite olfactory testing with odor thresholds of butanol-1, peppermint, lemon, clove, and ethyl acetate were carried out before surgery and after surgery at 1 and 3 months. Of 40 patients, 70% had symptoms of hyposmia or of anosmia before surgery, which dropped to 22.5% at 1 month after surgery and to 10% at 3 months after surgery. Nasal endoscopy and visual analog scale scores improved significantly. Odor threshold and odor identification scores also improved compared with the preoperative levels. A significant positive correlation was found between the threshold scores of butanol-1 and other odorants, both before and after surgery. Significant improvement was observed in olfaction after FESS, both in patient responses and in objective testing. The olfactory results with peppermint, lemon, clove, and ethyl acetate were close to those with butanol-1, and, hence, these other odorants can be used in place of butanol-1 in measuring the odor threshold.

Immunohistochemical characterization of human olfactory tissue

PubMed Central

Holbrook, Eric H.; Wu, Enming; Curry, William T.; Lin, Derrick T.; Schwob, James E.

2011-01-01

Objectives/Hypothesis The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction. Study Design An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies. Methods Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma. Results Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of the esthesioneuroblastoma. Conclusion The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurological disease. The similarities in human vs. rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology. PMID:21792956

Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

PubMed Central

Choi, Rhea

2018-01-01

Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

The prevalence of olfactory dysfunction in chronic rhinosinusitis.

PubMed

Kohli, Preeti; Naik, Akash N; Harruff, E Emily; Nguyen, Shaun A; Schlosser, Rodney J; Soler, Zachary M

2017-02-01

Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study were to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. A total of 47 articles were included in a systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin' Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96 ± 7.11 using the 40-item Smell Identification Test, 8.60 ± 2.81 using the Brief Smell Identification Test, 21.96 ± 8.88 using total Sniffin' Sticks score, 5.65 ± 1.51 using Sniffin' Sticks-Threshold, 9.21 ± 4.63 using Sniffin' Sticks-Discrimination, 9.47 ± 3.92 using Sniffin' Sticks-Identification, and 8.90 ± 5.14 using the Questionnaire for Olfactory Disorders-Negative Statements. In CRS populations, a significant percentage of patients experience olfactory dysfunction, and mean olfactory scores are within the dysosmic range. Laryngoscope, 2016 127:309-320, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice

PubMed Central

Pani, Amar K.; Jiao, Yun; Sample, Kenneth J.; Smeyne, Richard J.

2014-01-01

Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models. PMID:24642754

Alterations of brain grey matter density and olfactory bulb volume in patients with olfactory loss after traumatic brain injury.

PubMed

Han, Pengfei; Winkler, Nicole; Hummel, Cornelia; Hähner, Antje; Gerber, Johannes; Hummel, Thomas

2018-04-27

Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the grey matter (GM) density was examined for twenty-two TBI patients with hyposmia, twenty-four TBI patients with anosmia, and twenty-two age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2 weighted coronal slices using a standardized protocol. Brain lesions in the olfactory relevant areas were also examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC) and the temporal lobe pole, as compared to patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared to controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction compared to healthy controls. Smaller OB volumes were found for patients with olfactory loss as compared to controls. TBI patients with anosmia had the smallest OB volumes which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely depend on the location and severity of brain lesions in olfactory relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

Quality-space theory in olfaction

PubMed Central

Young, Benjamin D.; Keller, Andreas; Rosenthal, David

2014-01-01

Quality-space theory (QST) explains the nature of the mental qualities distinctive of perceptual states by appeal to their role in perceiving. QST is typically described in terms of the mental qualities that pertain to color. Here we apply QST to the olfactory modalities. Olfaction is in various respects more complex than vision, and so provides a useful test case for QST. To determine whether QST can deal with the challenges olfaction presents, we show how a quality space (QS) could be constructed relying on olfactory perceptible properties and the olfactory mental qualities then defined by appeal to that QS of olfactory perceptible properties. We also consider how to delimit the olfactory QS from other modalities. We further apply QST to the role that experience plays in refining our olfactory discriminative abilities and the occurrence of olfactory mental qualities in non-conscious olfactory states. QST is shown to be fully applicable to and useful for understanding the complex domain of olfaction. PMID:24474945

The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

PubMed

Courtiol, Emmanuelle; Wilson, Donald A

2017-01-01

Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

Dock and Pak regulate olfactory axon pathfinding in Drosophila.

PubMed

Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey

2003-04-01

The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

Acetylcholine and Olfactory Perceptual Learning

ERIC Educational Resources Information Center

Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

2004-01-01

Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform…

Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

NASA Astrophysics Data System (ADS)

Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

PubMed

Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

2015-02-15

Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p<0.001), albeit also better than patients with mild AD (p<.001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

Emotional stimulation alters olfactory sensitivity and odor judgment.

PubMed

Pollatos, Olga; Kopietz, Rainer; Linn, Jennifer; Albrecht, Jessica; Sakar, Vehbi; Anzinger, Andrea; Schandry, Rainer; Wiesmann, Martin

2007-07-01

Emotions have a strong influence on the perception of visual and auditory stimuli. Only little is known about the relation between emotional stimulation and olfactory functions. The present study investigated the relationship between the presentation of affective pictures, olfactory functions, and sex. Olfactory performance was assessed in 32 subjects (16 male). Olfactory sensitivity was significantly reduced following unpleasant picture presentation for all subjects and following pleasant picture presentation for male subjects only. Pleasantness and intensity ratings of a neutral suprathreshold odor were related to the valence of the pictures: After unpleasant picture presentation, the odor was rated as less pleasant and more intense, whereas viewing positive pictures induced a significant increase in reported odor pleasantness. We conclude that inducing a negative emotional state reduces olfactory sensitivity. A relation to functional deviations within the primary olfactory cortices is discussed.

Nested Expression Domains for Odorant Receptors in Zebrafish Olfactory Epithelium

NASA Astrophysics Data System (ADS)

Weth, Franco; Nadler, Walter; Korsching, Sigrun

1996-11-01

The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment.

PubMed

Huart, Caroline; Rombaux, Philippe; Gérard, Thomas; Hanseeuw, Bernard; Lhommel, Renaud; Quenon, Lisa; Ivanoiu, Adrian; Mouraux, André

2015-01-01

Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

The effect of olfactory training on the odor threshold in patients with traumatic anosmia.

PubMed

Jiang, Rong-San; Twu, Chih-Wen; Liang, Kai-Li

2017-09-01

Olfactory training is a novel intervention that has been used to treat olfactory dysfunction. This study attempted to investigate the effect of olfactory training in patients with traumatic anosmia. Patients with a clear history of anosmia after experiencing a head injury and whose phenyl ethyl alcohol (PEA) odor detection thresholds were -1 after steroid and zinc treatment were included. The patients were randomly divided into two groups, with patients in one group given a bottle of PEA and those in another group given a bottle of mineral oil for 3-month olfactory training. All the patients were followed up with a PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Magnetic resonance imaging was performed to measure the volume of the olfactory bulbs. Any patient whose PEA threshold result was below -1.01 or whose UPSIT-TC score increased four or more points was considered to have shown improvement in their olfactory function. Forty-two patients received PEA olfactory training, whereas 39 received olfactory training with mineral oil. The improvement of PEA thresholds function was observed in 10 patients within the PEA group and in 2 patients in the mineral oil group. The frequency of improvement of threshold within the PEA group was significantly higher than that of the mineral oil group. Neither olfactory bulb volume nor UPSIT-TC score was significantly different between the two groups. Our results showed that olfactory training with PEA can improve PEA odor threshold levels in patients with traumatic anosmia.

Office procedures for quantitative assessment of olfactory function.

PubMed

Doty, Richard L

2007-01-01

Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.

Neural Correlates of Olfactory Learning: Critical Role of Centrifugal Neuromodulation

ERIC Educational Resources Information Center

Fletcher, Max L.; Chen, Wei R.

2010-01-01

The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of…

An epigenetic state associated with areas of gene duplication

PubMed Central

Gimelbrant, Alexander A.; Chess, Andrew

2006-01-01

Asynchronous DNA replication is an epigenetically determined feature found in all cases of monoallelic expression, including genomic imprinting, X-inactivation, and random monoallelic expression of autosomal genes such as immunoglobulins and olfactory receptor genes. Most genes of the latter class were identified in experiments focused on genes functioning in the chemosensory and immune systems. We performed an unbiased survey of asynchronous replication in the mouse genome, excluding known asynchronously replicated genes. Fully 10% (eight of 80) of the genes tested exhibited asynchronous replication. A common feature of the newly identified asynchronously replicated areas is their proximity to areas of tandem gene duplication. Testing of other clustered areas supported the idea that such regions are enriched with asynchronously replicated genes. PMID:16687731

Olfactory-triggered panic attacks among Khmer refugees: a contextual approach.

PubMed

Hinton, Devon; Pich, Vuth; Chhean, Dara; Pollack, Mark

2004-06-01

One hundred Khmer refugees attending a psychiatric clinic were surveyed to determine the prevalence of olfactory-triggered panic attacks as well as certain characteristics of the episodes, including trigger (i.e. type of odor), frequency, length, somatic symptoms, and the rate of associated flashbacks and catastrophic cognitions. Forty-five of the 100 patients had experienced an olfactory-triggered panic attack in the last month. Trauma associations and catastrophic cognitions (e.g. fears of a 'wind attack', 'weakness', and 'weak heart') were common during events of olfactory panic. Several case examples are presented. A multifactorial model of the generation of olfactory panic is adduced. The therapeutic implications of this model for the treatment of olfactory panic are discussed.

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

PubMed Central

Féron, F.; Cochrane, J.; Bassingthwaighte, L.; Bayliss, C.; Davies, W.; Fronek, P.; Gray, C.; Kerr, G.; Licina, P.; Nowitzke, A.; Perry, C.; Silburn, P.A.S.; Urquhart, S.; Geraghty, T.

2008-01-01

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients. PMID:18689435

Molecular dissection of Norrie disease.

PubMed

Berger, W

1998-01-01

Norrie disease (ND) is a severe form of congenital blindness accompanied by mental retardation and/or deafness in at least one third of the patients. This article summarizes advances in the molecular genetic analysis of this disease during the last 13 years, including mapping and cloning of the human gene and the generation and characterization of a mouse model. Genetic linkage studies and physical mapping strategies have assigned the ND locus to the proximal short arm of the human X chromosome. The identification of chromosomal rearrangements in several patients, such as microdeletions, enabled the isolation of the ND gene by a positional cloning approach. Numerous point mutations in this gene have been identified in three distinct clinical entities: (1) ND, (2) familial and sporadic exudative vitreoretinopathy, and (3) retinopathy of prematurity. The gene encodes a relatively small protein, consisting of 133 amino acids. The function of the gene product is yet unknown, although homologies with known proteins and molecular modelling data suggest a role in the regulation of cell interaction or differentiation processes. A mouse model has been generated to shed more light on early pathogenic events involved in ND and allelic disorders. The mouse homologous protein is highly identical (94%) to the human polypeptide. The gene is expressed in the neuronal layers of the mouse retina, the cerebellum and olfactory epithelium. Mutant mice show snowflake-like opacities within the vitreous, dysgenesis of the ganglion cell layer and occasionally degeneration of photoreceptor cells. The mouse phenotype does not include phthisis bulbi and, overall, resembles a mild form of ND. Electrophysiological studies revealed a severely altered electroretinogram b-wave. These results suggest a primary defect in the inner neuronal layers of the retina. Defects in the vitreous and photoreceptor cell layer are most likely secondary effects. Further histological, functional and molecular studies of the mouse model are needed to provide additional information on disease associated pathways.

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

PubMed Central

Holmes, Holly E.; Powell, Nick M.; Ma, Da; Ismail, Ozama; Harrison, Ian F.; Wells, Jack A.; Colgan, Niall; O'Callaghan, James M.; Johnson, Ross A.; Murray, Tracey K.; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M. Jorge; Modat, Marc; O'Neill, Michael J.; Collins, Emily C.; Fisher, Elizabeth M. C.; Ourselin, Sébastien; Lythgoe, Mark F.

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. PMID:28408879

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

PubMed

Holmes, Holly E; Powell, Nick M; Ma, Da; Ismail, Ozama; Harrison, Ian F; Wells, Jack A; Colgan, Niall; O'Callaghan, James M; Johnson, Ross A; Murray, Tracey K; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M Jorge; Modat, Marc; O'Neill, Michael J; Collins, Emily C; Fisher, Elizabeth M C; Ourselin, Sébastien; Lythgoe, Mark F

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

Ionotropic crustacean olfactory receptors.

PubMed

Corey, Elizabeth A; Bobkov, Yuriy; Ukhanov, Kirill; Ache, Barry W

2013-01-01

The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs), the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs), as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

The Amelioration of Olfactory Acuity upon Sexual Maturation Might Affect Food Preferences

PubMed Central

Bignetti, Enrico; Sinesio, Fiorella; Aiello, Gaetano L.; Cannella, Carlo

2009-01-01

Upon sexual maturation, olfactory acuity in women ameliorates and starts oscillating across the cycle. During ovulation, mean olfactory threshold is 30 times lower than during bleeding. Interestingly, menstruated women undergo maleodorant trimethylaminuria. We argued that olfactory amelioration during ovulation might concur to a mating strategy, whereas olfactory impairment during bleeding might protect women against self-refusal. Testosterone and its 17β-estradiol derivative might be responsible for the synchronization of these menstrual events. Furthermore, we posed the question whether olfactory detection amelioration upon sexual maturation might provoke a change in food preferences, for instance a reduction in fish consumption. A preliminary survey in Italy provided encouraging results: 15-44 year-old women have lower fish consumption than 3-14 year-old girls. Surprisingly, men exhibited the same behaviour, so new olfactory tests as well as testosterone measurements are under way. PMID:22253964

Approaches for Assessing Olfaction in Children with Autism Spectrum Disorder.

PubMed

Kumazaki, Hirokazu; Okamoto, Masako; Kanzaki, Sho; Okada, Ken-Ichi; Mimura, Masaru; Minabe, Yoshio; Kikuchi, Mitsuru

2018-01-01

Olfactory traits in individuals with autism spectrum disorder (ASD) are considered the strongest predictors of social impairment. Compared to other sensory abnormalities, olfactory abnormalities in individuals with ASD are poorly understood. In this chapter, we provide an overview of the current assessment in individuals with ASD. Several confounding factors have to be considered when conducting research on olfaction in individuals with ASD. Qualitative measures of olfaction contain only limited information about the olfactory stimuli. In addition, little systematic information is available about individual's actual uses of olfaction in daily life. Only a limited number of experimental studies have performed quantitative measurements of olfactory abnormalities in ASD. Therefore, clarifying the relationship between olfactory traits and the influence of real-life situations in a laboratory setting is very difficult. Some new methodologies for measuring olfactory traits are gradually becoming available. New methods that reveal important links between ASD and olfactory traits should be developed in the future.

High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice

PubMed Central

Rivière, Sébastien; Soubeyre, Vanessa; Jarriault, David; Molinas, Adrien; Léger-Charnay, Elise; Desmoulins, Lucie; Grebert, Denise; Meunier, Nicolas; Grosmaitre, Xavier

2016-01-01

Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease. PMID:27659313

Long term serious olfactory loss in colds and/or flu.

PubMed

de Haro-Licer, Josep; Roura-Moreno, Jordi; Vizitiu, Anabella; González-Fernández, Adela; González-Ares, Josep Antón

2013-01-01

In the general population, we can find 2-3% of lifelong olfactory disorders (from hyposmia to anosmia). Two of the most frequent aetiologies are the common cold and flu. The aim of this study was to show the degree of long-term olfactory dysfunction caused by a cold or flu. This study was based on 240 patients, with olfactory loss caused only by flu or a cold. We excluded all patients with concomitant illness (66 patients), the rest of patients (n=174) consisted of 51 men (29.3%) and 123 women (70.7%). They all underwent olfactometry study (i and v cranial nerve) and a nasal sinus computed tomography scan, as well as magnetic resonance imaging of the brain. Results were compared with a control group (n=120). Very significant differences in levels of olfactory impairment for the olfactory nerve (P<.00001) and trigeminal nerve (P<.0001) were confirmed. People that suffer olfactory dysfunction for more than 6 months, from flu or a cold, present serious impairment of olfactory abilities. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Effects of diversity in olfactory environment on children's sense of smell.

PubMed

Martinec Nováková, Lenka; Fialová, Jitka; Havlíček, Jan

2018-02-13

Diversity in children's everyday olfactory environment may affect the development of their olfactory abilities and odor awareness. To test this, we collected data on olfactory abilities using the Sniffin' Sticks and odor awareness with Children's Olfactory Behaviors in Everyday Life Questionnaire in 153 preschool children and retested them one and a half year later. Parents completed an inventory on children's exposure to a variety of odors and on their own odor awareness using the Odor Awareness Scale. We controlled for the effects of age and verbal fluency on the children's performance. We found that the children's odor identification and discrimination scores differed as a function of parental odor awareness. Although these effects were rather small, they were commensurate in size with those of gender and age. To the best of our knowledge, this study is the first to present evidence that diversity in children's olfactory environment affects variation in their olfactory abilities and odor awareness. We suggest that future studies consider the long-term impact of perceptual learning out of the laboratory and its consequences for olfactory development.

An evaluation of olfactory function in adults with gastro-esophageal reflux disease.

PubMed

Günbey, Emre; Gören, İbrahim; Ünal, Recep; Yılmaz, Melikşah

2016-01-01

To the best of the authors' knowledge, this study is the first to evaluate the olfactory function of adult patients diagnosed with GERD. The results revealed that adults with GERD have diminished olfactory function. This study aimed to evaluate the olfactory abilities of subjects using the 'Sniffin' Sticks' olfactory test. A total of 35 men and women aged 18-60 years with a diagnosis of GERD and 45 healthy controls were included in the study. The Sniffin' Sticks olfactory test results of the two groups were compared, and the relationship between the study findings and the olfactory parameters was evaluated. The odor threshold (10.1; 9.5, p = 0.016), odor identification (9.6; 8.1, p < 0.001), and odor discrimination (10.7; 8.9, p < 0.001) of the GERD group were significantly lower than those of the control group. A statistically significant positive correlation was detected between the accompanying chronic pharyngitis, chronic sinusitis, and odor parameters. A significant correlation was not detected between the laryngeal findings and the olfactory parameters.

Evaluation of olfactory function in adults with primary hypothyroidism.

PubMed

Günbey, Emre; Karlı, Rıfat; Gökosmanoğlu, Feyzi; Düzgün, Berkan; Ayhan, Emre; Atmaca, Hulusi; Ünal, Recep

2015-10-01

Sufficient clinical data are not available on the effect of hypothyroidism on olfactory function in adults. In this study, we aimed to evaluate the olfactory function of adult patients diagnosed with primary hypothyroidism. Forty-five patients aged between 18 and 60 years who were diagnosed with clinical primary hypothyroidism and 45 healthy controls who had normal thyroid function tests were included in the study. Sniffin' Sticks olfactory test results of the 2 groups were compared. The relationships between thyroid function tests and olfactory parameters were evaluated. Odor threshold, identification, and discrimination scores of the hypothyroid group were significantly lower than those of the control group (p < 0.001). A significant positive correlation was detected between free triiodothyronine (FT3) levels and odor threshold, identification, and discrimination scores (p < 0.001). There was no significant relationship between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and olfactory parameters. Our study revealed diminished olfactory function in adults with hypothyroidism. FT3 levels were found to have a more significant relationship with olfactory parameters than TSH or FT4 levels. © 2015 ARS-AAOA, LLC.

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

PubMed

Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Olfactory function in psychotic disorders: Insights from neuroimaging studies

PubMed Central

Good, Kimberley P; Sullivan, Randii Lynn

2015-01-01

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

Mixture and odorant processing in the olfactory systems of insects: a comparative perspective.

PubMed

Clifford, Marie R; Riffell, Jeffrey A

2013-11-01

Natural olfactory stimuli are often complex mixtures of volatiles, of which the identities and ratios of constituents are important for odor-mediated behaviors. Despite this importance, the mechanism by which the olfactory system processes this complex information remains an area of active study. In this review, we describe recent progress in how odorants and mixtures are processed in the brain of insects. We use a comparative approach toward contrasting olfactory coding and the behavioral efficacy of mixtures in different insect species, and organize these topics around four sections: (1) Examples of the behavioral efficacy of odor mixtures and the olfactory environment; (2) mixture processing in the periphery; (3) mixture coding in the antennal lobe; and (4) evolutionary implications and adaptations for olfactory processing. We also include pertinent background information about the processing of individual odorants and comparative differences in wiring and anatomy, as these topics have been richly investigated and inform the processing of mixtures in the insect olfactory system. Finally, we describe exciting studies that have begun to elucidate the role of the processing of complex olfactory information in evolution and speciation.

The activity-dependent histone variant H2BE modulates the life span of olfactory neurons

PubMed Central

Santoro, Stephen W; Dulac, Catherine

2012-01-01

We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. DOI: http://dx.doi.org/10.7554/eLife.00070.001 PMID:23240083

Olfactory Impairment in Chronic Rhinosinusitis Using Threshold, Discrimination, and Identification Scores

PubMed Central

Kohli, Preeti; Storck, Kristina A.; Schlosser, Rodney J.

2016-01-01

Differences in testing modalities and cut-points used to define olfactory dysfunction contribute to the wide variability in estimating the prevalence of olfactory dysfunction in chronic rhinosinusitis (CRS). The aim of this study is to report the prevalence of olfactory impairment using each component of the Sniffin’ Sticks test (threshold, discrimination, identification, and total score) with age-adjusted and ideal cut-points from normative populations. Patients meeting diagnostic criteria for CRS were enrolled from rhinology clinics at a tertiary academic center. Olfaction was assessed using the Sniffin’ Sticks test. The study population consisted of 110 patients. The prevalence of normosmia, hyposmia, and anosmia using total Sniffin’ Sticks score was 41.8%, 20.0%, and 38.2% using age-appropriate cut-points and 20.9%, 40.9%, and 38.2% using ideal cut-points. Olfactory impairment estimates for each dimension mirrored these findings, with threshold yielding the highest values. Threshold, discrimination, and identification were also found to be significantly correlated to each other (P < 0.001). In addition, computed tomography scores, asthma, allergy, and diabetes were found to be associated with olfactory dysfunction. In conclusion, the prevalence of olfactory dysfunction is dependent upon olfactory dimension and if age-adjusted cut-points are used. The method of olfactory testing should be chosen based upon specific clinical and research goals. PMID:27469973

Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish.

PubMed

Harden, Maegan V; Newton, Lucy A; Lloyd, Russell C; Whitlock, Kathleen E

2006-11-01

Odors experienced as juveniles can have significant effects on the behavior of mature organisms. A dramatic example of this occurs in salmon, where the odors experienced by developing fish determine the river to which they return as adults. Further examples of olfactory memories are found in many animals including vertebrates and invertebrates. Yet, the cellular and molecular bases underlying the formation of olfactory memory are poorly understood. We have devised a series of experiments to determine whether zebrafish can form olfactory memories much like those observed in salmonids. Here we show for the first time that zebrafish form and retain olfactory memories of an artificial odorant, phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate that exposure to PEA results in changes in gene expression within the olfactory sensory system. These changes are evident by in situ hybridization in the olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA. This increase is evident at 2-3 days postfertilization and is maintained in the adult animals. We propose that the changes in otx2 gene expression are manifest as an increase in the number of neuronal precursors in the cells olfactory epithelium of the odor-exposed fish. Thus, our results reveal a role for the environment in controlling gene expression in the developing peripheral nervous system. Copyright 2006 Wiley Periodicals, Inc.

Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction.

PubMed

Zhao, Kai; Scherer, Peter W; Hajiloo, Shoreh A; Dalton, Pamela

2004-06-01

Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (

Predictors of Olfactory Dysfunction in Rhinosinusitis Using the Brief Smell Identification Test

PubMed Central

Alt, Jeremiah A.; Mace, Jess C.; Buniel, Maria C. F.; Soler, Zachary M.; Smith, Timothy L.

2014-01-01

Objective Associations between olfactory function to quality-of-life (QOL) and disease severity in patients with rhinosinusitis is poorly understood. We sought to evaluate and compare olfactory function between subgroups of patients with rhinosinusitis using the Brief Smell Identification Test (BSIT). Study Design Cross-sectional evaluation of a multi-center cohort. Methods Patients with recurrent acute sinusitis (RARS) and chronic rhinosinusitis (CRS) with and without nasal polyposis were prospectively enrolled from three academic tertiary care sites. Each subject completed the BSIT, in addition to measures of disease-specific QOL. Patient demographics, comorbidities, and clinical measures of disease severity were compared between patients with normal (BSIT; ≥9) and abnormal (BSIT; <9) olfaction scores. Regression modeling was used to identify potential risk factors associated with olfactory impairment. Results Patients with rhinosinusitis (n=445) were found to suffer olfactory dysfunction as measured by the BSIT (28.3%). Subgroups of rhinosinusitis differed in the degree of olfactory dysfunction reported. Worse disease severity, measured by computed tomography and nasal endoscopy, correlated to worse olfaction. Olfactory scores did not consistently correlate with Rhinosinusitis Disability Index or Sinonasal Outcome Test scores. Regression models demonstrated nasal polyposis was the strongest predictor of olfactory dysfunction. Recalcitrant disease and aspirin intolerance were strongly predictive of worse olfactory function. Conclusion Olfactory dysfunction is a complex, multi-factorial process found to be differentially expressed within subgroups of rhinosinusitis. Olfaction was associated with disease severity as measured by imaging and endoscopy, with only weak associations to disease-specific QOL measures. PMID:24402746

Evolutionary Genomics of Genes Involved in Olfactory Behavior in the Drosophila melanogaster Species Group

PubMed Central

Lavagnino, Nicolás; Serra, François; Arbiza, Leonardo; Dopazo, Hernán; Hasson, Esteban

2012-01-01

Previous comparative genomic studies of genes involved in olfactory behavior in Drosophila focused only on particular gene families such as odorant receptor and/or odorant binding proteins. However, olfactory behavior has a complex genetic architecture that is orchestrated by many interacting genes. In this paper, we present a comparative genomic study of olfactory behavior in Drosophila including an extended set of genes known to affect olfactory behavior. We took advantage of the recent burst of whole genome sequences and the development of powerful statistical tools to analyze genomic data and test evolutionary and functional hypotheses of olfactory genes in the six species of the Drosophila melanogaster species group for which whole genome sequences are available. Our study reveals widespread purifying selection and limited incidence of positive selection on olfactory genes. We show that the pace of evolution of olfactory genes is mostly independent of the life cycle stage, and of the number of life cycle stages, in which they participate in olfaction. However, we detected a relationship between evolutionary rates and the position that the gene products occupy in the olfactory system, genes occupying central positions tend to be more constrained than peripheral genes. Finally, we demonstrate that specialization to one host does not seem to be associated with bursts of adaptive evolution in olfactory genes in D. sechellia and D. erecta, the two specialists species analyzed, but rather different lineages have idiosyncratic evolutionary histories in which both historical and ecological factors have been involved. PMID:22346339

Olfactory short-term memory encoding and maintenance - an event-related potential study.

PubMed

Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

2014-09-01

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model. Copyright © 2014 Elsevier Inc. All rights reserved.

Olfactory Functioning in First-Episode Psychosis.

PubMed

Kamath, Vidyulata; Lasutschinkow, Patricia; Ishizuka, Koko; Sawa, Akira

2018-04-06

Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Olfaction variation in mouse husbandry and its implications for refinement and standardization: UK survey of animal scents.

PubMed

López-Salesansky, Noelia; Mazlan, Nur H; Whitfield, Lucy E; Wells, Dominic J; Burn, Charlotte C

2016-10-01

Olfaction plays a crucial role in mouse communication, providing information about genetic identity, physiological status of conspecifics and alerting mice to potential predators. Scents of animal origin can trigger physiological and behavioural responses that could affect experimental responses and impact positively or negatively on mouse welfare. Additionally, differing olfactory profiles could help explain variation in results between laboratories. A survey was sent to animal research units in the UK to investigate potential transfer of scents of animal origin during routine husbandry procedures, and responses were obtained from animal care workers and researchers using mice in 51 institutions. The results reveal great diversity between animal units regarding the relevant husbandry routines covered. Most [71%] reported housing non-breeding male and female mice in the same room, with 76% reporting that hands were not washed and gloves not changed between handling male and female mice. The most commonly reported species housed in the same facility as mice was the rat (91%), and 41% of respondents were aware that scents from rats could affect mice. Changing of gloves between handling mice and other species was reported by 79% of respondents. Depending on the aspect considered, between 18 and 33% of respondents believed human and non-human animal odours would strongly affect mouse physiology, behaviour or standardization, while approximately 32-54% believed these effects would be weak. This indicates uncertainty regarding the significance of these factors. Understanding and controlling these practices could reduce unwanted variability in experimental results and maximize welfare. © The Author(s) 2015.

[Organization of olfactory system of the Indian major carp Labeo rohita (Ham.): a study using scanning and transmission microscopy].

PubMed

Bhute, Y V; Baile, V V

2007-01-01

Catla catla, Labeo rohita, and Cirrhinus mrigala are important alimentary fish in India. Their reproduction (breeding) depends on season. The fish perceive external factors-stimuli and chemical signals through the olfactory system that plays the key role in the central regulation of reproduction. However, in the available literature, any electron microscopy data on organization of olfactory elements in these fish are absent. We have studied ultrastructure of the olfactory organ in male L. rohita by using scanning (SEM) and transmission electron microscopy (TEM). The olfactory organ consists of olfactory epithelium, a short nerve, and olfactory bulb. The organ has oval shape and consists of approximately 47-52 lamellae in adult fish and of 14-20 lamellae in fish at the stage of fingerling. These lamellae originate from the midline raphe. By using SEM, the presence of microvillar sensory and ciliated non-sensory cells in these lamellae is shown. By using TEM, a microvillar receptor cell is revealed, which has rough endoplasmic reticulum and Golgi apparatus towards the apical end. Basal cells are found at the base of the receptor cell; supporting cells are located adjacent to olfactory receptor neurons, while epithelial cells--in the non-sensory part of olfactory epithelium. Mast, blastema and macrophages cells are also found in the basal lamina. This work is the first publication on structural organization of olfactory system of the Indian major carp, which provides information about morphological and ultrastructural organization of olfactory system and opens new opportunities for study of chemical neuroanatomy, sensory signal processing, and nervous regulation of reproduction of the Indian major carp.

Neuropeptide Y in the olfactory system, forebrain and pituitary of the teleost, Clarias batrachus.

PubMed

Gaikwad, Archana; Biju, K C; Saha, Subhash G; Subhedar, Nishikant

2004-03-01

Distribution of neuropeptide Y (NPY)-like immunoreactivity in the forebrain of catfish Clarias batrachus was examined with immunocytochemistry. Conspicuous immunoreactivity was seen in the olfactory receptor neurons (ORNs), their projections in the olfactory nerve, fascicles of the olfactory nerve layer in the periphery of bulb and in the medial olfactory tracts as they extend to the telencephalic lobes. Ablation of the olfactory organ resulted in loss of immunoreactivity in the olfactory nerve layer of the bulb and also in the fascicles of the medial olfactory tracts. This evidence suggests that NPY may serve as a neurotransmitter in the ORNs and convey chemosensory information to the olfactory bulb, and also to the telencephalon over the extrabulbar projections. In addition, network of beaded immunoreactive fibers was noticed throughout the olfactory bulb, which did not respond to ablation experiment. These fibers may represent centrifugal innervation of the bulb. Strong immunoreactivity was encountered in some ganglion cells of nervus terminalis. Immunoreactive fibers and terminal fields were widely distributed in the telencephalon. Several neurons of nucleus entopeduncularis were moderately immunoreactive; and a small population of neurons in nucleus preopticus periventricularis was also labeled. Immunoreactive terminal fields were particularly conspicuous in the preoptic, the tuberal areas, and the periventricular zone around the third ventricle and inferior lobes. NPY immunoreactive cells and fibers were detected in all the lobes of the pituitary gland. Present results describing the localization of NPY in the forebrain of C. batrachus are in concurrence with the pattern of the immunoreactivity encountered in other teleosts. However, NPY in olfactory system of C. batrachus is a novel feature that suggests a role for the peptide in processing of chemosensory information.

How much does nasal cavity morphology matter? Patterns and rates of olfactory airflow in phyllostomid bats

PubMed Central

Eiting, Thomas P.; Perot, J. Blair; Dumont, Elizabeth R.

2015-01-01

The morphology of the nasal cavity in mammals with a good sense of smell includes features that are thought to improve olfactory airflow, such as a dorsal conduit that delivers odours quickly to the olfactory mucosa, an enlarged olfactory recess at the back of the airway, and a clear separation of the olfactory and respiratory regions of the nose. The link between these features and having a good sense of smell has been established by functional examinations of a handful of distantly related mammalian species. In this paper, we provide the first detailed examination of olfactory airflow in a group of closely related species that nevertheless vary in their sense of smell. We study six species of phyllostomid bats that have different airway morphologies and foraging ecologies, which have been linked to differences in olfactory ability or reliance. We hypothesize that differences in morphology correlate with differences in the patterns and rates of airflow, which in turn are consistent with dietary differences. To compare species, we make qualitative and quantitative comparisons of the patterns and rates of airflow through the olfactory region during both inhalation and exhalation across the six species. Contrary to our expectations, we find no clear differences among species in either the patterns of airflow through the airway or in rates of flow through the olfactory region. By and large, olfactory airflow seems to be conserved across species, suggesting that morphological differences appear to be driven by other mechanical demands on the snout, such as breathing and feeding. Olfactory ability may depend on other aspects of the system, such as the neurobiological processing of odours that work within the existing morphology imposed by other functional demands on the nasal cavity. PMID:25520358

Preservation of olfaction in surgery of olfactory groove meningiomas.

PubMed

Jang, Woo-Youl; Jung, Shin; Jung, Tae-Young; Moon, Kyung-Sub; Kim, In-Young

2013-08-01

Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of "Sniffin'Sticks" test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient's age, and gender were analyzed with attention to the post-operative olfactory function. Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size<4 cm and 42.3% in size>4 cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). If the tumor was smaller than 4 cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review.

PubMed

Ajmani, Gaurav S; Suh, Helen H; Pinto, Jayant M

2016-11-01

Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution-related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683-1693; http://dx.doi.org/10.1289/EHP136.

Reorganization of neuronal circuits of the central olfactory system during postprandial sleep

PubMed Central

Yamaguchi, Masahiro; Manabe, Hiroyuki; Murata, Koshi; Mori, Kensaku

2013-01-01

Plastic changes in neuronal circuits often occur in association with specific behavioral states. In this review, we focus on an emerging view that neuronal circuits in the olfactory system are reorganized along the wake-sleep cycle. Olfaction is crucial to sustaining the animals' life, and odor-guided behaviors have to be newly acquired or updated to successfully cope with a changing odor world. It is therefore likely that neuronal circuits in the olfactory system are highly plastic and undergo repeated reorganization in daily life. A remarkably plastic feature of the olfactory system is that newly generated neurons are continually integrated into neuronal circuits of the olfactory bulb (OB) throughout life. New neurons in the OB undergo an extensive selection process, during which many are eliminated by apoptosis for the fine tuning of neuronal circuits. The life and death decision of new neurons occurs extensively during a short time window of sleep after food consumption (postprandial sleep), a typical daily olfactory behavior. We review recent studies that explain how olfactory information is transferred between the OB and the olfactory cortex (OC) along the course of the wake-sleep cycle. Olfactory sensory input is effectively transferred from the OB to the OC during waking, while synchronized top-down inputs from the OC to the OB are promoted during the slow-wave sleep. We discuss possible neuronal circuit mechanisms for the selection of new neurons in the OB, which involves the encoding of olfactory sensory inputs and memory trace formation during waking and internally generated activities in the OC and OB during subsequent sleep. The plastic changes in the OB and OC are well coordinated along the course of olfactory behavior during wakefulness and postbehavioral rest and sleep. We therefore propose that the olfactory system provides an excellent model in which to understand behavioral state-dependent plastic mechanisms of the neuronal circuits in the brain. PMID:23966911

Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease.

PubMed

Ma, Weiwei; Wu, Mengnan; Zhou, Siyan; Tao, Ye; Xie, Zuolei; Zhong, Yi

2018-05-20

Emerging evidence suggests that neuro-inflammation begins early and drives the pathogenesis of Alzheimer's disease (AD), and anti-inflammatory therapies are under clinical development. However, several anti-inflammatory compounds failed to improve memory in clinical trials, indicating that reducing inflammation alone might not be enough. On the other hand, neuro-inflammation is implicated in a number of mental disorders which share the same therapeutic targets. Based on these observations, we screened a batch of genes related with mental disorder and neuro-inflammation in a classical olfactory conditioning in an amyloid beta (Aβ) overexpression fly model. A Smoothened (SMO) mutant was identified as a genetic modifier of Aβ toxicity in 3-min memory and downregulation of SMO rescued Aβ-induced 3-min and 1-h memory deficiency. Also, Aβ activated innate inflammatory response in fly by increasing the expression of antimicrobial peptides, which were alleviated by downregulating SMO. Furthermore, pharmaceutical administration of a SMO antagonist LDE rescued Aβ-induced upregulation of SMO in astrocytes of mouse hippocampus, improved memory in Morris water maze (MWM), and reduced expression of astrocyte secreting pro-inflammatory factors IL-1β, TNFα and the microglia marker IBA-1 in an APP/PS1 transgenic mouse model. Our study suggests that SMO is an important conserved modulator of Aβ toxicity in both fly and mouse models of AD. Copyright © 2018. Published by Elsevier Ltd.

Host-location behavior of the tea green leafhopper Empoasca vitis Göthe (Hemiptera: Cicadellidae): olfactory and visual effects on their orientation.

PubMed

Zhang, X; Pengsakul, T; Tukayo, M; Yu, L; Fang, W; Luo, D

2017-09-25

The tea green leafhopper, Empoasca vitis Göthe, is one of the most serious pests in tea growing areas. This study investigated the roles played by olfaction and vision in host orientation behavior. The compound eye of E. vitis was found to be a photopic eye; few olfactory sensilla were found on the antennae, while abundant gustatory sensilla were recorded on the mouthparts. Three opsin genes (EV_LWop, EV_UVop, EV_Bop) were isolated and found to be mainly expressed in the compound eye compared with other parts of the body. Immunolocalization indicated that the opsins mainly located in the different regions of rhabdom. The transcription levels of EV_LWop, EV_Bop and EV_UVop were reduced by 77.3, 70.0 and 40.0%, respectively, by RNA interference induced by being fed a special RNA-rich diet for 6 days. The rate of tropism to host color was effectively impaired by 67.6 and 29.5% in the dsEV_LWop and dsEV_Bop treatment groups, but there was no significant change in the dsEV_UVop group. The determination of the cause of the tropism indicated that odors from the host over long distances were unable to attract E. vitis and were only detected when the insects were close to the host. The developed compound eye of E. vitis plays a leading role in host location, and the long-wavelength opsin significantly affects the tropism to host color; the lack of olfactory sensilla results in long-distance odors not being able to be detected until the insect is near to the host-plant. The understanding of these behavioral mechanisms, especially the importance of opsin genes is expected to be useful for pest management.

Olfactory-Triggered Panic Attacks Among Khmer Refugees: A Contextual Approach

PubMed Central

Hinton, Devon; Pich, Vuth; Chhean, Dara; Pollack, Mark

2009-01-01

One hundred Khmer refugees attending a psychiatric clinic were surveyed to determine the prevalence of olfactory-triggered panic attacks as well as certain characteristics of the episodes, including trigger (i.e. type of odor), frequency, length, somatic symptoms, and the rate of associated flashbacks and catastrophic cognitions. Forty-five of the 100 patients had experienced an olfactory-triggered panic attack in the last month. Trauma associations and catastrophic cognitions (e.g. fears of a ‘wind attack,’ ‘weakness,’ and ‘weak heart’) were common during events of olfactory panic. Several case examples are presented. A multifactorial model of the generation of olfactory panic is adduced. The therapeutic implications of this model for the treatment of olfactory panic are discussed. PMID:15446720

Smelling time: a neural basis for olfactory scene analysis

PubMed Central

Ache, Barry W.; Hein, Andrew M.; Bobkov, Yuriy V.; Principe, Jose C.

2016-01-01

Behavioral evidence from phylogenetically diverse animals and humans suggests that olfaction could be much more involved in interpreting space and time than heretofore imagined by extracting temporal information inherent in the olfactory signal. If this is the case, the olfactory system must have neural mechanisms capable of encoding time at intervals relevant to the turbulent odor world in which many animals live. We review evidence that animals can use populations of rhythmically active or ‘bursting’ olfactory receptor neurons (bORNs) to extract and encode temporal information inherent in natural olfactory signals. We postulate that bORNs represent an unsuspected neural mechanism through which time can be accurately measured, and that ‘smelling time’ completes the requirements for true olfactory scene analysis. PMID:27594700

The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

PubMed

Yu, Yiqun; Moberly, Andrew H; Bhattarai, Janardhan P; Duan, Chen; Zheng, Qian; Li, Fangqi; Huang, Hugh; Olson, William; Luo, Wenqin; Wen, Tieqiao; Yu, Hongmeng; Ma, Minghong

2017-09-27

Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5 + cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP + cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5 + cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons. Copyright © 2017 the authors 0270-6474/17/379403-12$15.00/0.

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

PubMed

Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

2016-07-01

Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. © 2015 Society for the Study of Addiction.

High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb.

PubMed

Hoffmann, Angelika; Kunze, Reiner; Helluy, Xavier; Milford, David; Heiland, Sabine; Bendszus, Martin; Pham, Mirko; Marti, Hugo H

2016-01-01

Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema.

Characterization of carboxypeptidase A6, an extracellular matrix peptidase.

PubMed

Lyons, Peter J; Callaway, Myrasol B; Fricker, Lloyd D

2008-03-14

Carboxypeptidase A6 (CPA6) is a member of the M14 metallocarboxypeptidase family that is highly expressed in the adult mouse olfactory bulb and broadly expressed in embryonic brain and other tissues. A disruption in the human CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection. In this study the cellular distribution, processing, and substrate specificity of human CPA6 were investigated. The 50-kDa pro-CPA6 is routed through the constitutive secretory pathway, processed by furin or a furin-like enzyme into the 37-kDa active form, and secreted into the extracellular matrix. CPA6 cleaves the C-terminal residue from a range of substrates, including small synthetic substrates, larger peptides, and proteins. CPA6 has a preference for large hydrophobic C-terminal amino acids as well as histidine. Peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides were found to be processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. Whereas CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, CPA6 converts inactive angiotensin I into the biologically active angiotensin II. Taken together, these data suggest a role for CPA6 in the regulation of neuropeptides in the extracellular environment within the olfactory bulb and other parts of the brain.

Odour maps in the brain of butterflies with divergent host-plant preferences.

PubMed

Carlsson, Mikael A; Bisch-Knaden, Sonja; Schäpers, Alexander; Mozuraitis, Raimondas; Hansson, Bill S; Janz, Niklas

2011-01-01

Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca(2+) activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.

Odour Maps in the Brain of Butterflies with Divergent Host-Plant Preferences

PubMed Central

Schäpers, Alexander; Mozuraitis, Raimondas; Hansson, Bill S.; Janz, Niklas

2011-01-01

Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants. PMID:21901154

Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

PubMed

Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

2018-06-07

Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

A cytological and experimental study of the neuropil and primary olfactory afferences to the piriform cortex.

PubMed

Vargas-Barroso, Víctor; Larriva-Sahd, Jorge

2013-09-01

The microscopic organization of the piriform cortex (PC) was studied in normal and experimental material from adult albino rats. In rapid-Golgi specimens a set of collaterals from the lateral olfactory tract (i.e., sublayer Ia) to the neuropil of the Layer II (LII) was identified. Specimens from experimental animals that received electrolytic lesion of the main olfactory bulb three days before sacrificing, were further processed for pre-embedding immunocytochemistry to the enzyme glutamic acid decarboxylase 67 (GAD 67). This novel approach permitted a simultaneous visualization at electron microscopy of both synaptic degeneration and GAD67-immunoreactive (GAD-I) sites. Degenerating and GAD-I synapses were separately found in the neuropil of Layers I and II of the PC. Previously overlooked patches of neuropil were featured in sublayer Ia. These areas consisted of dendritic and axonal processes including four synaptic types. Tridimensional reconstructions from serial thin sections from LI revealed the external appearance of the varicose and tubular dendrites as well as the synaptic terminals therein. The putative source(s) of processes to the neuropil of sublayer Ia is discussed in the context of the internal circuitry of the PC and an alternative model is introduced. Copyright © 2013 Wiley Periodicals, Inc.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

PubMed

Charbel Issa, Peter; Reuter, Peggy; Kühlewein, Laura; Birtel, Johannes; Gliem, Martin; Tropitzsch, Anke; Whitcroft, Katherine L; Bolz, Hanno J; Ishihara, Kenji; MacLaren, Robert E; Downes, Susan M; Oishi, Akio; Zrenner, Eberhart; Kohl, Susanne; Hummel, Thomas

2018-05-24

Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Olfactory deposition of inhaled nanoparticles in humans

PubMed Central

Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

2016-01-01

Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

Diagnosis and clinical characteristics of congenital anosmia: case series report.

PubMed

Qu, Qiuyi; Liu, Jianfeng; Ni, Daofeng; Zhang, Qiuhang; Yang, Dazhang; Wang, Naya; Wu, Xueyan; Han, Honglei

2010-12-01

congenital anosmia is extremely rare and tends to present late. We report on a series of patients with congenital anosmia to analyze its clinical characteristics and present illustrative cases. retrospective chart review. tertiary care centre. thirty-five patients with congenital anosmia were reviewed. A thorough medical history taking, physical examination, and nasal endoscopy were performed in all patients. T&T olfactory testing (n = 33), olfactory event-related potentials (OERPs) (n = 33), and sinonasal computed tomography (CT) (n = 35) were carried out. Magnetic resonance images (MRIs) of the olfactory pathway (n = 34) were available. Serum sex hormones were tested (n = 33). physical examination, olfactory testing, MRI of the olfactory pathway, and serum sex hormones. twenty cases were isolated congenital anosmia (ICA). Fifteen cases were congenital anosmia with other anomalies, including 12 cases with Kallmann syndrome (KS), two with CHARGE syndrome, and one with hypoplasia of the nasal cavity and nasal sinus. T&T olfactory testing indicated anosmia (n = 33). No OERP was obtained (n = 33). CT scans indicated three abnormal patients, including two with unilateral choanal atresia and one with hypoplasia of the nasal cavity and sinus. MRI demonstrated aplasia or hypoplasia of the olfactory bulbs, tracts, and olfactory sulci (n = 34). Serum sex hormones were low in 12 patients with KS. early diagnosis of congenital anosmia on the basis of olfactory symptoms is difficult. MRI of the olfactory pathway plays an important role in anatomic location. ICA is the most common congenital anosmia. KS is the primary presentation of congenital anosmia with other anomalies.

The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input.

PubMed

He, Chao; Altshuler-Keylin, Svetlana; Daniel, David; L'Etoile, Noelle D; O'Halloran, Damien

2016-10-06

In mammals, olfactory subsystems have been shown to express seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-one-neuron pattern, whereas in Caenorhabditis elegans, olfactory sensory neurons express multiple G-protein coupled odorant receptors per olfactory sensory neuron. In both mammalian and C. elegans olfactory sensory neurons (OSNs), the process of olfactory adaptation begins within the OSN; this process of negative feedback within the mammalian OSN has been well described in mammals and enables activated OSNs to desensitize their response cell autonomously while attending to odors detected by separate OSNs. However, the mechanism that enables C. elegans to adapt to one odor and attend to another odor sensed by the same olfactory sensory neuron remains unclear. We found that the cyclic nucleotide gated channel subunit CNG-1 is required to promote cross adaptation responses between distinct olfactory cues. This change in sensitivity to a pair of odorants after persistent stimulation by just one of these odors is modulated by the internal nutritional state of the animal, and we find that this response is maintained across a diverse range of food sources for C. elegans. We also reveal that CNG-1 integrates food related cues for exploratory motor output, revealing that CNG-1 functions in multiple capacities to link nutritional information with behavioral output. Our data describes a novel model whereby CNG channels can integrate the coincidence detection of appetitive and olfactory information to set olfactory preferences and instruct behavioral outputs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence of olfactory impairment in older adults.

PubMed

Murphy, Claire; Schubert, Carla R; Cruickshanks, Karen J; Klein, Barbara E K; Klein, Ronald; Nondahl, David M

2002-11-13

Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. To determine the prevalence of olfactory impairment in older adults. A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.

Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

PubMed Central

Martin, Claire; Ravel, Nadine

2014-01-01

Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to “bind” distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15–40 Hz) and gamma (60–100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory. PMID:25002840

Gray Matter Volume Reduction of Olfactory Cortices in Patients With Idiopathic Olfactory Loss

PubMed Central

Yao, Linyin; Pinto, Jayant Marian; Yi, Xiaoli; Li, Li; Peng, Peng

2014-01-01

Idiopathic olfactory loss (IOL) is a common olfactory disorder. Little is known about the pathophysiology of this disease. Previous studies demonstrated decreased olfactory bulb (OB) volume in IOL patients when compared with controls. The aim of our study was to investigate structural brain alterations in areas beyond the OB. We acquired T1-weighted magnetic resonance images from 16 patients with IOL and from 16 age- and sex-matched controls on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. Psychophysical testing confirmed that patients had higher scores for Toyota and Takagi olfactometer and lower scores for Sniffin’ Sticks olfactory test than controls (t = 46.9, P < 0.001 and t = 21.4, P < 0.001, respectively), consistent with olfactory dysfunction. There was a significant negative correlation between the 2 olfactory tests (r = −0.6, P = 0.01). In a volume of interest analysis including primary and secondary olfactory areas, we found patients with IOL to exhibit gray matter volume loss in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal cortex, and the piriform cortex. The present study indicates that changes in the central brain structures proximal to the OB occur in IOL. Further investigations of this phenomenon may be helpful to elucidate the etiology of IOL. PMID:25240014

Expression of calmodulin mRNA in rat olfactory neuroepithelium.

PubMed

Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

1991-04-01

A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

Histological properties of the nasal cavity and olfactory bulb of the Japanese jungle crow Corvus macrorhynchos.

PubMed

Yokosuka, Makoto; Hagiwara, Akiko; Saito, Toru R; Tsukahara, Naoki; Aoyama, Masato; Wakabayashi, Yoshihiro; Sugita, Shoei; Ichikawa, Masumi

2009-09-01

The nasal cavity and olfactory bulb (OB) of the Japanese jungle crow (Corvus macrorhynchos) were studied using computed tomography (CT) and histochemical staining. The nasal septum divided the nasal cavity in half. The anterior and maxillary conchae were present on both sides of the nasal cavity, but the posterior concha was indistinct. A small OB was present on the ventral surface of the periphery of the cerebrum. The OB-brain ratio--the ratio of the size of the OB to that of the cerebral hemisphere--was 6.13. The olfactory nerve bundles projected independently to the OB, which appeared fused on gross examination. Histochemical analysis confirmed the fusion of all OB layers. Using a neural tracer, we found that the olfactory nerve bundles independently projected to the olfactory nerve layer (ONL) and glomerular layer (GL) of the left and right halves of the fused OB. Only 4 of 21 lectins bound to the ONL and GL. Thus, compared with mammals and other birds, the jungle crow may have a poorly developed olfactory system and an inferior sense of olfaction. However, it has been contended recently that the olfactory abilities of birds cannot be judged from anatomical findings alone. Our results indicate that the olfactory system of the jungle crow is an interesting research model to evaluate the development and functions of vertebrate olfactory systems.

Differences in peripheral sensory input to the olfactory bulb between male and female mice

NASA Astrophysics Data System (ADS)

Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

2017-04-01

Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

Expression of corticosteroid binding globulin in the rat olfactory system.

PubMed

Dölz, Wilfried; Eitner, Annett; Caldwell, Jack D; Jirikowski, Gustav F

2013-05-01

Glucocorticoids are known to act on the olfactory system although their mode of action is still unclear since nuclear glucocorticoid receptors are mostly absent in the olfactory mucosa. In this study we used immunocytochemistry, in situ hybridization, and RT-PCR to study the expression and distribution of corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet cells could be immunostained for CBG. Nasal secretion contained measurable amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was localized in many of the basal cells of the olfactory mucosa, while mature sensory cells contained CBG only in processes as determined by double immunostaining with the olfactory marker protein OMP. This staining was most pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non-sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb indicated axonal transport. Portions of the periglomerular cells, the mitral cells and the tufted cells were also CBG positive. CBG encoding transcripts were confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG may be significant for uptake, accumulation and transport of glucocorticoids, including aerosolic cortisol. Copyright © 2012 Elsevier GmbH. All rights reserved.

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

PubMed Central

Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

2009-01-01

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

Odor Coding in the Maxillary Palp of the Malaria Vector Mosquito Anopheles gambiae

PubMed Central

Lu, Tan; Qiu, Yu Tong; Wang, Guirong; Kwon, Jae Young; Rutzler, Michael; Kwon, Hyung-Wook; Pitts, R. Jason; van Loon, Joop J.A.; Takken, Willem; Carlson, John R.; Zwiebel, Laurence J.

2011-01-01

Summary Background Many species of mosquitoes, including the major malaria vector Anopheles gambiae, utilize carbon dioxide (CO2) and 1-octen-3-ol as olfactory cues in host-seeking behaviors that underlie their vectorial capacity. However, the molecular and cellular basis of such olfactory responses remains largely unknown. Results Here, we use molecular and physiological approaches coupled with systematic functional analyses to define the complete olfactory sensory map of the An. gambiae maxillary palp, an olfactory appendage that mediates the detection of these compounds. In doing so, we identify three olfactory receptor neurons (ORNs) that are organized in stereotyped triads within the maxillary-palp capitate-peg-sensillum population. One ORN is CO2-responsive and characterized by the coexpression of three receptors that confer CO2 responses, whereas the other ORNs express characteristic odorant receptors (AgORs) that are responsible for their in vivo olfactory responses. Conclusions Our results describe a complete and highly concordant map of both the molecular and cellular olfactory components on the maxillary palp of the adult female An. gambiae mosquito. These results also facilitate the understanding of how An. gambiae mosquitoes sense olfactory cues that might be exploited to compromise their ability to transmit malaria. PMID:17764944