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Disruption of GABA(A) receptors on GABAergic interneurons leads to increased oscillatory power in the olfactory bulb network.

Synchronized neural activity is believed to be essential for many CNS functions, including neuronal development, sensory perception, and memory formation. In several brain areas GABA(A) receptor-mediated synaptic inhibition is thought to be important for the generation of synchronous network activity. We have used GABA(A) receptor beta3 subunit deficient mice (beta3-/-) to study the role of GABAergic inhibition in the generation of network oscillations in the olfactory bulb (OB) and to reveal the role of such oscillations in olfaction. The expression of functional GABA(A) receptors was drastically reduced (>93%) in beta3-/- granule cells, the local inhibitory interneurons of the OB. This was revealed by a large reduction of muscimol-evoked whole-cell current and the total current mediated by spontaneous, miniature inhibitory postsynaptic currents (mIPSCs). In beta3-/- mitral/tufted cells (principal cells), there was a two-fold increase in mIPSC amplitudes without any significant change in their kinetics or frequency. In parallel with the altered inhibition, there was a significant increase in the amplitude of theta (80% increase) and gamma (178% increase) frequency oscillations in beta3-/- OBs recorded in vivo from freely moving mice. In odor discrimination tests, we found beta3-/- mice to be initially the same as, but better with experience than beta3+/+ mice in distinguishing closely related monomolecular alcohols. However, beta3-/- mice were initially better and then worse with practice than control mice in distinguishing closely related mixtures of alcohols. Our results indicate that the disruption of GABA(A) receptor-mediated synaptic inhibition of GABAergic interneurons and the augmentation of IPSCs in principal cells result in increased network oscillations in the OB with complex effects on olfactory discrimination, which can be explained by an increase in the size or effective power of oscillating neural cell assemblies among the mitral cells of beta3-/- mice.

Animals↗

Food odor thresholds in relation to age, nutritional, and health status.

Odor perception plays an important role in nutrition. In the present study, the effect of aging and health status on detection of food odors is shown and interrelations with nutritional status are explored. We have tested 26 healthy young (20-25 yrs) and 23 elderly (61-74 yrs) subjects who were screened according to the SENIEUR protocol. Anthropometric measures and blood samples provided 20 parameters of nutritional status. A validated measurement procedure under forced choice conditions was used to quantify the detection thresholds of two food odors of which one had a trigeminal effect and the other mainly had an olfactory effect. There is a significant declining sensitivity for both odors. Our observations indicate that a relation between nutrition and odor perception in the elderly population exists. Whether olfactory deficits cause or are caused by increased nutritional risk deserves further study.

Adult↗

Evidence for separate perceptive and semantic memories for odours: a priming experiment.

Sixty-four subjects participated in an olfactory priming experiment comprising separate study and test phases. Priming was measured within the olfactory modality (intramodal condition) and from the visual modality to the olfactory modality (intermodal condition). In the study phase of the intramodal condition, subjects were exposed twice to a series of odours: once performing a semantic orientation task (deciding which of seven categories odour stimuli belonged to) and once performing a perceptual orientation task (judging the intensity, the hedonicity and the familiarity of odour stimuli). Half of the odour stimuli corresponded to edible products, the other half did not. The study phase of the intermodal condition was similar, with the exception that the names of the odours (instead of the odours themselves) were presented. In the test phase, subjects were presented with primed and non-primed odour targets and had to decide as fast as possible whether the target corresponded to an edible product or not. Response times and types were recorded by a computer. The analysis of response times revealed a priming effect in the intramodal condition only. Results are discussed in terms of separate perceptual and semantic subsystems that store odour representations.

Adolescent↗

A phenomenological model of the perceived intensity of single odorants.

The response of a model olfactory system to a single odorant is quantified by interconnecting three separate stimulus-response relationships. Together, these relationships encompass the deposition of odorant molecules onto an olfactory organ, their movement to the dendrite of the olfactory receptor neuron, their subsequent induction of action potentials, and the processing of induced and spontaneous action potentials by the central nervous system, resulting in perception and a behavioral response. Phenomena discussed within the context of the model include the behavioral threshold, central summation of responses from a number of olfactory neurons, and the effect of organ shape on olfactory detection. The intent of the model is to provide a quantitative conceptual framework for designing and interpreting experiments relating sensory input to perception and behavior. Its utility is particularly evident for insect olfaction since it enables insect sex pheromone behavioral thresholds to be estimated from the literature when bioassays or electrophysiological studies are not possible. It also derives a physiologically meaningful method for comparing behavioral thresholds among different animals, and permits comparisons of different kinds of behavioral responses in the same species. Vertebrate olfaction is treated briefly in a discussion of the effect of sniffing on the threshold of detection.

Action Potentials↗

Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

Adolescent↗

Olfactory regulation of maternal behavior in mammals.

In mammals, olfactory cues are extensively used in many aspects of maternal care to ensure the coordination of mother-infant interactions and consequently the normal development of the offspring. Outside the period of parturition and lactation, when the young are not a behavioral priority, olfactory cues play an inhibitory role on maternal responsiveness since in most mammalian species studied so far, nonpregnant females find the odor of young aversive. On the contrary at the time of parturition, a shift in the hedonic value of infantile odors occurs so that the young now become a very potent stimulus and this sensorial processing constitutes an important part of the maternal motivational system. Moreover, infants' odors provide a basis for individual recognition by their mothers and some species (ungulates) have developed highly specialized mechanisms for processing of the infant signals. Perception of the smell of the young also regulates various aspects of maternal behavior. Dodecyl propionate, a compound released by of pup's preputial glands, has been shown to influence anogenital licking behavior, a fundamental pattern of maternal behavior in rodents. While there is no functional specificity of either the main or the accessory olfactory systems in the development of maternal behavior amongst species, it appears that only the main olfactory system is implicated when individual odor discrimination of the young is required. Neural structures, such as the main olfactory bulb, undergo profound changes when exposed to offspring odors at parturition. These changes in synaptic circuitry contribute both to maternal responsiveness to these odors, to their memorization, and to effects of long-term maternal experience.

Animals↗

Memantine fails to facilitate partial cigarette deprivation in smokers--no role of Memantine in the treatment of nicotine dependency?

The efficacy of Memantine in the treatment of nicotine dependency in humans remained to be evaluated. The aims of our pilot study were to investigate (1) the effectiveness of Memantine in facilitating smoking reduction and (2) the influence of Memantine on the perception of nicotine. In order to achieve these aims we conducted a placebo controlled double-blind parallel group study in smokers (n = 20 per group). Before the beginning of the treatment-phase (10/20 mg Memantine per day) all participants were instructed to reduce smoking (partial deprivation). Before and during partial deprivation we registered the daily cigarette consumption and craving estimates. Following nasal stimulation with nicotine enantiomers hedonic and intensity estimates and the discrimination ability were assessed. Memantine failed to facilitate smoking reduction and did not influence the perception of nicotine with the exception of a weak reduction of olfactory intensity estimates reaching statistical significance for one nicotine enantiomer only.

Adult↗

Hallucinations.

Hallucinations, sensory perceptions without environmental stimuli, occur as simple experiences of auditory, gustatory, olfactory, tactile, or visual phenomena as well as mixed- or complex experiences of more than one simple phenomenon. The nature of the hallucination assists localization, differential diagnosis, and treatment planning. In particular, the presence of persistent visual hallucinations of persons with Parkinson's disease predicts dementia, rapid deterioration, permanent nursing home placement, and death. Hallucinations in persons with Alzheimer's disease are often associated with serious behavioral problems and predict a rapid cognitive decline. Theories of the etiology of hallucinations include (1) stimulation, e.g., neurochemical, electrical, seizure, and ephaptic, and (2) inhibition, e.g., destruction of normally inhibitory functions, resulting in disinhibition as in the Charles Bonnet and phantom limb syndromes. Functional neuroimaging procedures suggest anatomical associations for hallucinations. While hallucinations may be a symptom of medical, neurologic, and psychiatric disorders, they may also occur in a wide range of human experiences.

Hallucinations↗

Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study.

Studies of patients with focal brain injury indicate that smell perception involves caudal orbitofrontal and medial temporal cortices, but a more precise functional organization has not been characterized. In addition, although it is believed that odors are potent triggers of emotion, support for an anatomical association is scant. We sought to define the neural substrates of human olfactory information processing and determine how these are modulated by affective properties of odors. We used event-related functional magnetic resonance imaging (fMRI) in an olfactory version of a classical conditioning paradigm, whereby neutral faces were paired with pleasant, neutral, or unpleasant odors, under 50% reinforcement. By comparing paired (odor/face) and unpaired (face only) conditions, odor-evoked neural activations could be isolated specifically. In primary olfactory (piriform) cortex, spatially and temporally dissociable responses were identified along a rostrocaudal axis. A nonhabituating response in posterior piriform cortex was tuned to all odors, whereas activity in anterior piriform cortex reflected sensitivity to odor affect. Bilateral amygdala activation was elicited by all odors, regardless of valence. In posterior orbitofrontal cortex, neural responses evoked by pleasant and unpleasant odors were segregated within medial and lateral segments, respectively. The results indicate functional heterogeneity in areas critical to human olfaction. They also show that brain regions mediating emotional processing are differentially activated by odor valence, providing evidence for a close anatomical coupling between olfactory and emotional processes.

Adolescent↗

Changes in odor quality discrimination following recovery from olfactory nerve transection.

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.

Animals↗

Functional characterization of olfactory binding proteins for appeasing compounds and molecular cloning in the vomeronasal organ of pre-pubertal pigs.

The appeasing behaviour of pre-pubertal pigs appears to result from the perception of maternal odours (fatty acids) and of steroids coming from the male. We have used a ligand-oriented approach to functionally characterize olfactory binding proteins involved in the detection of appeasing compounds in the nasal mucosa (NM) and the vomeronasal organ (VNO) of pre-pubertal pigs. Several proteins were identified, combining binding assay, immunodetection and protein sequencing. Their sites of expression in nasal and vomeronasal tissues were studied by reverse transcription polymerase chain reaction (RT-PCR). The proteins belong to the lipocalin superfamily: Alpha-1-acid glycoprotein (AGP), odorant-binding protein (OBP), salivary lipocalin (SAL) and Von Ebner's gland protein (VEG), and displayed different binding capacities for the appeasing compounds. RT-PCR experiments showed that OBP and VEG are expressed not only in the NM, but also in the VNO and that SAL is only expressed in the VNO. This is the first report of the expression of these lipocalins in the VNO. Different binding affinities between lipocalins and appeasing compounds, together with their different localizations in the olfactory systems, suggest multiple possibilities for the peripheral coding of appeasing signals.

Amino Acid Sequence↗

Discrimination of odors in olfactory bulb, pyriform-amygdaloid areas, and orbitofrontal cortex of the monkey.

In the orbitofrontal olfactory area (LPOF) which was delineated in a previous paper, the capacity for odor discrimination was studied and compared with that in the anterior pyriform cortex (AP), the medial portion of the amygdala (MA), and the olfactory bulb (OB). Unanesthetized monkeys were used and eight odors were applied. 1. In the OB, 12.5% of the cells responded to only one odor, and the cells which responded to five odors were most numerous (25%). The total of the cells which responded to two, three, and four odors was 52%, which was less than the total of the cells responding to three, four, and five odors (67.5%). A small number oc cells responded to all eight odors (2.5%). The responses were classified as an increase (+type), a decrease (-type), or no change (no-type) in the rate of spike discharge. 2. In the AP and MA, no difference in the response patterns was found. The cells which responded to only one odor were 12.3% of the total, and the cells which responded to three different kinds of odors were most numerous (34.3%). The total of the cells responding to two, three, and four odors was 80%, much more than that in the OB. In addition, no cell responded to all eight odors. Concerning the response types, an increase followed by a decrease, or vice versa, in the rate of spike discharges (mixed-type) was observed which did not appear in the OB. Thus, an advance was found in the processing of olfactory information when compared with the OB. 3. A most striking finding in the LPOF was that 50% of the cells responded to only one odor. The cells which responded to two, three, and four odors decreased in this order, and no cell responded to more than five odors. These cells never responded to light or sound. 4. Using three very similar odors and five very different odors, it was apparent that the ability to discriminate odors of the same category is far more advanced in the LPOF than in the lower olfactory areas; and, in contrast, the lower olfactory areas also play a significant role in the discrimination of odors which belong to different categories. 5. It was concluded that the capacity for odor discrimination definitely improves along the olfactory nervous system from the lower to the higher areas. It is highly probable that a fine and sepcific discrimination of odors is performed in the LPOF.

Amygdala↗

Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli.

More chemicals can be smelled than there are olfactory receptors for them, necessitating a combinatorial representation by somewhat broadly tuned receptors. To understand the perception of odor quality and concentration, it is essential to establish the nature of the receptor repertoires that are activated by particular odorants at particular concentrations. We have taken advantage of the one-to-one correspondence of glomeruli and olfactory receptor molecules in the mouse olfactory bulb to analyze the tuning properties of a major receptor population by high resolution calcium imaging of odor responses selectively in the presynaptic compartment of glomeruli. We show that eighty different olfactory receptors projecting to the dorsal olfactory bulb respond to high concentrations of aldehydes with limited specificity. Varying ensembles of about 10 to 20 receptors encode any particular aldehyde at low stimulus concentrations with high specificity. Even normalized odor response patterns are markedly concentration dependent, caused by pronounced differences in affinity within the aldehyde receptor repertoire.

Aldehydes↗

Odorant-specific patterns of sniffing during imagery distinguish 'bad' and 'good' olfactory imagers.

There are large individual differences in the self-reported ability to form vivid olfactory mental imagery. Based on such self-reports, subjects have been classified as 'bad' or 'good' imagers. The present study examined whether a differential strategy in re-enacting the olfactomotor response during imagery may explain the dissociation between 'bad' and 'good' olfactory imagers. As previously reported, odor imagery was accompanied by sniffing. Although 'bad' and 'good' olfactory imagers did not differ in their overall sniffing volume, they used different strategies when re-enacting the motor component of olfaction during imagery. Particularly, as in real perception, 'good' but not 'bad' imagers generated bigger sniffs when imagining a pleasant smell compared with an unpleasant smell (P<0.02). Furthermore, preventing sniffing significantly hampered mental imagery of pleasant odors in 'good' but not 'bad' imagers (P<0.03). Taken together, these results suggest (i) the validity of the dissociation between 'bad' and 'good' olfactory imagers as revealed by self-report; (ii) that sniffing may be a causal factor in the creation of olfactory imagery; and (iii) that sniff measurements may serve as a reliable non-verbal tool in exploring individual differences in odor imagery.

Animals↗

[Heterogeneity of molecular mechanisms the olfactor reception].

In experiments on the frog isolated olfactory epithelium by using vital fluorescent microscope, odorants with fruit, rank, flower and camphor smell were shown to involve intracellular signaling systems in olfactory transduction. The odorants with different qualitative smells have different messenger and activity mechanisms. Intracellular messengers do not participate in reception of odorants with piquant and rotten smells. Thus the perception of different odour substances is maintained by physical and chemical processes. Hence, not only taste, carotid, medullar, but olfactory reception as well are characterised by heterogeneity of biophysical mechanisms.

Animals↗

Odorant intensity as a determinant for olfactory conditioning in honeybees: roles in discrimination, overshadowing and memory consolidation.

Stimulus intensity is an important determinant for perception, learning and behaviour. We studied the effects of odorant concentration on classical conditioning involving odorants and odorant-mechanosensory compounds using the proboscis-extension reflex in the honeybee. Our results show that high concentrations of odorant (a) support better discrimination in a feature-positive task using rewarded odorant-mechanosensory compounds versus unrewarded mechanosensory stimuli, (b) have a stronger capacity to overshadow learning of a simultaneously trained mechanosensory stimulus, and (c) induce better memory consolidation. Furthermore, honeybees were trained discriminatively to two different concentrations of one odorant. Honeybees are not able to solve this task when presented with rewarded low versus unrewarded high concentrations. Taken together, our results suggest that high concentrations of odorant support stronger associations (are more 'salient') than low concentrations. Our results, however, do not indicate that honeybees can treat two different concentrations of one odorant as qualitatively different stimuli. These findings fill a gap in what is known about honeybee olfactory learning and are a first step in relating behaviour to recent advances in the physiological analysis of coding for odorant concentration in honeybees.

Animals↗

Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress.

The effects of olfactory bulbectomy on the acoustic startle reflex and shock-induced sensitization of the startle reflex were examined in 3 experiments. In Experiment 1, bulbectomized animals showed a modest increase in baseline startle responding following surgery, and normal acquisition of fear-potentiated startle, but a pronounced increase in baseline startle responding during the course of conditioning relative to sham-operated controls. In Experiments 2 and 3, bulbectomized animals showed shock-induced sensitization of the startle reflex to shock intensities that did not produce sensitization in sham and unoperated controls. These data suggest that olfactory bulbectomy results in an increased vulnerability to stressors, which may be mediated by a disinhibition of the amygdala or other structures involved in mediating stress and anxiety. Thus, the olfactory bulbectomy model of depression may share some similarities with other stress-induced models of depression.

Acoustic Stimulation↗