Usefulness of the odor stick identification test for Japanese patients with olfactory dysfunction

The odor stick identification test (OSIT) is a new test of olfactory function recently developed for Japanese people. The purpose of the present study was to evaluate this test in relation to T&T olfactometry and the cross-cultural smell identification test (CC-SIT) by applying to 110 Japanese patients with olfactory disturbance. The averaged recognition thresholds for five odorants in T&T olfactometry, the number of correct answers in the CC-SIT and the rates of identification of 13 odorants in the OSIT were compared. The visual analogue scale (VAS) was also used to evaluate symptoms. The rate of identification of OSIT showed high and significant correlation coefficients with the averaged recognition thresholds of T&T olfactometry (-0.766, P < 0.001), with the number of correct answers in CC-SIT (0.754, P < 0.001) and with the VAS score (0.591, P < 0.001). In addition, on the identification performance measured by OSIT, we found significant differences between all pairs of four degrees of olfactory dysfunction except for one pair. Thus, we conclude that OSIT is useful for evaluating olfactory dysfunction in Japanese people.     

Disrupted Functional Connectivity of the Anterior Cingulate Cortex in Cirrhotic Patients without Overt Hepatic Encephalopathy: A Resting State fMRI Study

Background

To evaluate the changes of functional connectivity of the anterior cingulate cortex (ACC) in patients with cirrhosis without overt hepatic encephalopathy (HE) using resting state functional MRI.

Methodology/Principal Findings

Participants included 67 cirrhotic patients (27 minimal hepatic encephalopathy (MHE) and 40 cirrhotic patients without MHE (non-HE)), and 40 age- and gender- matched healthy controls. rsfMRI were performed on 3 Telsa scanners. The pregenual ACC resting-state networks (RSNs) were characterized by using a standard seed-based whole-brain correlation method and compared between cirrhotic patients and healthy controls. Pearson correlation analysis was performed between the ACC RSNs and venous blood ammonia levels, neuropsychological tests (number connection test type A [NCT-A] and digit symbol test [DST]) scores in cirrhotic patients. All thresholds were set at P<0.05, with false discovery rate corrected. Compared with controls, non-HE and MHE patients showed significantly decreased functional connectivity in the bilateral ACC, bilateral middle frontal cortex (MFC), bilateral middle cingulate cortex (MCC), bilateral superior temporal gyri (STG)/middle temporal gyri (MTG), bilateral thalami, bilateral putamen and bilateral insula, and increased functional connectivity of bilateral precuneus and left temporo-occipital lobe and bilateral lingual gyri. Compared with non-HE patients, MHE showed the decreased functional connectivity of right MCC, bilateral STG/MTG and right putamen. This indicates decreased ACC functional connectivity predominated with the increasing severity of HE. NCT-A scores negatively correlated with ACC functional connectivity in the bilateral MCC, right temporal lobe, and DST scores positively correlated with functional connectivity in the bilateral ACC and the right putamen. No correlation was found between venous blood ammonia levels and functional connectivity in ACC in cirrhotic patients.

Conclusions/Significance

Disrupted functional connectivity in ACC was found in cirrhotic patients which further deteriorated with the increasing severity of HE and correlated cognitive dysfunction in cirrhotic patients.     

Sniff magnitude test: relationship to odor identification, detection, and memory tests in a clinic population

Recently a novel measure of olfactory function, the Sniff Magnitude Test (SMT), was developed that relies on changes in inhalation in response to an odor. The relationship of this unique test to that of other olfactory tests has received little investigation. In this study, we assessed, in 132 patients presenting to a chemosensory disorders clinic, the relationship of SMT scores to those from 3 standardized psychophysical tests: the University of Pennsylvania Smell Identification Test (UPSIT), a phenyl ethyl alcohol odor detection threshold test, and a short-term odor memory/discrimination test. SMT scores were roughly related to olfactory dysfunction categories defined for the UPSIT and correlated moderately with the other tests. Malodors (1% and 3% methylthiobutyrate [MTB], 1% ethyl 3-mercaptoproprionate) exhibited stronger correlations than nonmalodors (3% phenyl ethyl alcohol [PEA], 3% amyl acetate, 3% n-butanol) and elicited greater sniff suppression. In a principal component analysis, the SMT measures loaded on components different from those of the other tests, which loaded on a separate component. Anticipatory responses (i.e., smaller sniffs) occurred across trials for the first malodor (1% MTB), but not for the first nonmalodor (3% PEA), that was encountered. These results, along with those of an earlier factor analysis, suggest that sniff magnitude is influenced by odorant quality and intensity, as well as by cognitive factors.     

Demographic and cognitive predictors of cued odor identification: evidence from a population-based study

This study investigated demographic and cognitive correlates of cued odor identification in a population-based sample from the Betula project: 1906 healthy adults varying in age from 45 to 90 years were assessed in a number of tasks tapping various cognitive domains, including cognitive speed, semantic memory and executive functioning. The results revealed a gradual and linear deterioration in cued odor identification across the adult life span. Overall, females identified more odors than men, although men and women performed at the same level in the oldest age cohort (85-90 years). Hierarchical regression analyses revealed that age, sex, education, cognitive speed and vocabulary were reliable correlates of performance in the odor identification task. In addition, age-related deficits in the included demographic and cognitive variables could not fully account for the observed age-related impairment in identification, suggesting that additional factors are underlying the observed deterioration. Likely candidates here are sensory abilities such as olfactory detection and discrimination.     

Oridonin prevents insulin resistance–mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) was characterized for cognitive dysfunction. Insulin resistance (IR) has been identified to be correlated with the pathogenesis of MHE. Oridonin (Ori) is an active terpenoid, which has been reported to rescue synaptic loss and restore insulin sensitivity. In this study, we found that intraperitoneal injection of Ori rescued IR, reduced the autophagosome formation and synaptic loss and improved cognitive dysfunction in MHE rats. Moreover, in insulin‐resistant PC12 cells and N2a cells, we found that Ori blocked IR‐induced synaptic deficits via the down‐regulation of PTEN, the phosphorylation of Akt and the inhibition of autophagy. Taken together, these results suggested that Ori displays therapeutic efficacy towards memory deficits via improvement of IR in MHE and represents a novel bioactive therapeutic agent for treating MHE.     

Structural and Functional Abnormalities of Default Mode Network in Minimal Hepatic Encephalopathy: A Study Combining DTI and fMRI

Background and Purpose

Live failure can cause brain edema and aberrant brain function in cirrhotic patients. In particular, decreased functional connectivity within the brain default-mode network (DMN) has been recently reported in overt hepatic encephalopathy (HE) patients. However, so far, little is known about the connectivity among the DMN in the minimal HE (MHE), the mildest form of HE. Here, we combined diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to test our hypothesis that both structural and functional connectivity within the DMN were disturbed in MHE.

Materials and Methods

Twenty MHE patients and 20 healthy controls participated in the study. We explored the changes of structural (path length, tracts count, fractional anisotropy [FA] and mean diffusivity [MD] derived from DTI tractography) and functional (temporal correlation coefficient derived from rs-fMRI) connectivity of the DMN in MHE patients. Pearson correlation analysis was performed between the structural/functional indices and venous blood ammonia levels/neuropsychological tests scores of patients. All thresholds were set at P<0.05, Bonferroni corrected.

Results

Compared to the healthy controls, MHE patients showed both decreased FA and increased MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to left parahippocampal gyrus (PHG), and decreased functional connectivity between the PCC/PCUN and left PHG, and medial prefrontal cortex (MPFC). MD values of the tract connecting PCC/PCUN to the left PHG positively correlated to the ammonia levels, the temporal correlation coefficients between the PCC/PCUN and the MPFC showed positive correlation to the digital symbol tests scores of patients.

Conclusion

MHE patients have both disturbed structural and functional connectivity within the DMN. The decreased functional connectivity was also detected between some regions without abnormal structural connectivity, suggesting that the former may be more sensitive in detecting the early abnormalities of MHE. This study extends our understanding of the pathophysiology of MHE.     

Olfactory function in patients with hypogonadotropic hypogonadism: an all-or-none phenomenon?

Hypogonadotropic hypogonadism (HH) refers to an endocrine defectof hypothalamic origin resulting in gonadal hypoplasia and frequentlyassociated with anosmia or severely impaired olfactory function(Kallmann's syndrome). This apparently results from a disruptionin the migration of neurons from the olfactory placode to thebulb and hypothalamus early in development, and so providesa unique opportunity to investigate olfactory function in humansubjects with congenitally incomplete peripheral systems. Olfactoryperformance in 37 HH patients and 37 age-matched controls wascompared using a modified version of the Munich Olfaction Test.This test is based on the sniff-bottle method and includes testsof (i) odor quality discrimination, (ii) intensity discrimination,(iii) detection thresholds, and (iv) recognition, hedonic evaluationand identification ability. The patients could be divided intotwo distinct groups differing significantly on all four subtestsand showing no overlap in performance: 20 anosmics, conformingto Kallmann's syndrome, and 17 apparent normosmics whose performancewas slightly poorer, but not significantly different to thatof the controls. The unexpected failure to find a continuumof olfactory dysfunction now raises the question whether HHwith or without anosmia represents two syndromes with distinctetiologies, or rather reflects the ability of the olfactorysystem to function well despite morphological impairment.     

昆虫气味认知的嗅觉神经结构及分子机制

大多数昆虫主要通过气味认知感知外界环境的变化,维持生命活动。探究昆虫气味认知的嗅觉系统神经结构及分子机制,对于完善气味认知神经生物学理论及利用其原理进行仿生学研究等有重要的科学意义。近年,关于昆虫气味认知科学研究有了很大的进展。本文从昆虫神经生物学的视角详细综述了近年关于昆虫气味认知的嗅觉神经结构、分子机制及气味信号的神经传导途径等方面的基本理论及最新研究成果。综述结果显示:昆虫对气味的认知是通过嗅觉神经系统的触角感器、触角叶(AL)、蕈形体(MB)等脑内多层信号处理神经结构来实现的。当外界气味分子进入触角感器内后,由感器内特定的气味识别蛋白(OBP)将气味分子运载到达嗅觉感受神经元(ORN)树突膜上的受体位点,气味分子与表达特定气味的受体(OR)结合产生电信号,并以动作电位的形式通过ORN的轴突传到脑内的触角叶。在触角叶经过嗅觉纤维球对气味信息选择性加工处理,再由投射神经元(PNs)将初步的识别和分类的气味信息传到蕈形体和外侧角(LH)等神经中枢,实现对气味的识别和认知。虽然,近年昆虫气味认知神经生物学的研究有了很大的进步,但是,我们认为目前的研究成果还不能完全阐明昆虫气味认知的神经机制,还有很多问题,例如,触角叶上众多的嗅觉纤维球是如何对嗅觉感受神经元传入的气味信息进行编码处理的?等有待进一步深入研究。为了搞清这些疑难问题,我们认为需要提高现有的实验技术水平,加强电生理学和分子神经生物学相结合的实验研究,从分子水平探究气味认知的神经机制可能是未来研究的热点。     

The effect of hepatic encephalopathy, hepatic failure, and portosystemic shunt on brain volume of cirrhotic patients: a voxel-based morphometry study

Purpose

To evaluate the effect of hepatic encephalopathy (HE), hepatic failure, and portosystemic shunt (PS) on the brain volume alteration in cirrhotic patients with MRI voxel-based morphometry (VBM).

Methods

Sixty cirrhotic patients (overt HE [OHE], n = 11; minimal HE [MHE], n = 19; non HE [nHE], n = 30) including 12 with pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) scanning and 40 healthy controls were recruited. Neuropsychological and laboratory tests were performed in all patients. VBM was analyzed with ANOVA test among 4 groups, and t-tests for patients with different hepatic function, PS scores, and TIPS. Multiple linear regression was performed to investigate the effect of venous blood ammonia levels, Child-Pugh scores, and PS on the brain volumes in all patients.

Results

Cirrhotic patients exhibited decreased volume in many areas of gray matter (GM), increased volume in thalamus, and increased whiter matter (WM) volume, with the extent of affected brain volume greater in HE patients than nHE patients. Hepatic failure also resulted in decreased GM volume. Patients with high PS scores and TIPS displayed decreased GM and increased WM volume in some regions. Post-TIPS patients displayed increased GM volume in the thalamus. Multiple covariate regression results suggested that Child-Pugh score was a major factor to affect GM volume, while PS mainly affected WM volume.

Conclusion

Brain structure abnormalities appeared bilaterally symmetrical in cirrhotic patients, and the impairment was more extensive in HE patients than those without HE. Increased thalamus volume was not associated with HE progression. Hepatic failure and PS altered cirrhotic patients’ brain structure.     

Semantic Factors in Episodic Recognition of Common Odors in Early and Late Adulthood: a Review

Information on long-term memory for common odors is discussed.Olfactory parameters (i. e. familiarity, recognition, identification)and their relationship to current memory theory are highlighted.Emphasis is focused on the impact of semantic memory on episodicodor recognition. In contrast to previous research suggestingthat verbal/semantic factors play a negligible role in olfactorymemory, the present review indicates that episodic odor informationis mediated by factors that can be subsumed under the rubricof semantic memory. Specific odor knowledge, such as perceivedfamiliarity and identifiability, is strongly and positivelyrelated to episodic odor memory performance. Age-related impairmentsin various olfactory and cognitive parameters and the potentialdetrimental effects in episodic odor memory are discussed. Finally,the issue of whether olfactory memory should be conceptualizedas an independent process, or whether it shares characteristicswith memory for verbal and visual information, is addressed.Chem. Senses 22: 623–633, 1997.     

Olfactory metacognition

The current paper focuses on the subjective knowledge people have about their ability to name odors. Previous investigations of such metacognitive aspects of olfactory cognition are very scarce and have yielded results that need further scrutiny. In two experiments, we investigated three metamemory judgments about odor identity. As opposed to previous findings, participants' feeling of knowing judgments about odor identity predicted later recognition. Participants were also accurate but highly overconfident in their retrospective confidence in odor identification. A strong and imminent feeling of being able to name an odor, a so-called 'tip of the nose' experience, was found to predict later recall, but was otherwise poorly related to any partial activation of the odor name or other information associated with the odor. This makes it different from the commonly investigated 'tip of the tongue' phenomenon. The current study shows that olfactory metamemory is related to actual knowledge, a finding that is in line with what has been observed for other modalities.     

Altered regional homogeneity in the development of minimal hepatic encephalopathy: a resting-state functional MRI study

Background

Little is known about how spontaneous brain activity progresses from non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this study was to evaluate the evolution pattern of spontaneous brain activities in cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo) method.

Methodology/Principal Findings

Resting-state fMRI data were acquired in 47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age-and sex-matched healthy controls. The Kendall’s coefficient of concordance (KCC) was used to measure the regional homogeneity. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symbol test (DST) scores, venous blood ammonia levels. Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST scores positively correlated with ReHo values in the cuneus, precuneus and lingual gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected).

Conclusions/Significance

Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE.     

Spared Piriform Cortical Single-Unit Odor Processing and Odor Discrimination in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer''s disease is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest reported signs of Alzheimer''s disease is olfactory dysfunction, which may manifest in a variety of ways. The present study sought to address this issue by investigating odor coding in the anterior piriform cortex, the primary cortical region involved in higher order olfactory function, and how it relates to performance on olfactory behavioral tasks. An olfactory habituation task was performed on cohorts of transgenic and age-matched wild-type mice at 3, 6 and 12 months of age. These animals were then anesthetized and acute, single-unit electrophysiology was performed in the anterior piriform cortex. In addition, in a separate group of animals, a longitudinal odor discrimination task was conducted from 3–12 months of age. Results showed that while odor habituation was impaired at all ages, Tg2576 performed comparably to age-matched wild-type mice on the olfactory discrimination task. The behavioral data mirrored intact anterior piriform cortex single-unit odor responses and receptive fields in Tg2576, which were comparable to wild-type at all age groups. The present results suggest that odor processing in the olfactory cortex and basic odor discrimination is especially robust in the face of amyloid β precursor protein (AβPP) over-expression and advancing amyloid β (Aβ) pathology. Odor identification deficits known to emerge early in Alzheimer''s disease progression, therefore, may reflect impairments in linking the odor percept to associated labels in cortical regions upstream of the primary olfactory pathway, rather than in the basic odor processing itself.     

Development of a smell identification test using a novel stick-type odor presentation kit

The odor identification is strongly influenced by the social and cultural factors; therefore, the odorants used in a smell identification test should be familiar to the test population. In addition, the device used in the test is desired to be simply handled and retain odor quality over time. We developed a novel stick-type odor presentation kit that consists of microcapsules of odorant incorporated into stable cream and the smell identification test using it. Thirteen odorants were selected to be familiar to the test population. In the test, we used two identification methods: one was a modified forced-choice paradigm with "detectable but not recognizable" and "no smell detected" added as choices and the other was a two-step identification paradigm where the participant first selected one of eight odor categories and then chose the specific odor name from the selected category. We verified the performance of the odor stick and the test by stability, using a test-retest paradigm, comparing this test with another smell test, and testing Japanese people from a range of age groups. We conclude that this kit is a useful odor presentation device, and the test using it works effectively as a smell identification test.     

Loss of smelling is an early marker of aging and is associated with inflammation and DNA damage in C57BL/6J mice

Olfactory dysfunction is a prevalent symptom and an early marker of age-related neurodegenerative diseases in humans, including Alzheimer's and Parkinson's Diseases. However, as olfactory dysfunction is also a common symptom of normal aging, it is important to identify associated behavioral and mechanistic changes that underlie olfactory dysfunction in nonpathological aging. In the present study, we systematically investigated age-related behavioral changes in four specific domains of olfaction and the molecular basis in C57BL/6J mice. Our results showed that selective loss of odor discrimination was the earliest smelling behavioral change with aging, followed by a decline in odor sensitivity and detection while odor habituation remained in old mice. Compared to behavioral changes related with cognitive and motor functions, smelling loss was among the earliest biomarkers of aging. During aging, metabolites related with oxidative stress, osmolytes, and infection became dysregulated in the olfactory bulb, and G protein coupled receptor-related signaling was significantly down regulated in olfactory bulbs of aged mice. Poly ADP-ribosylation levels, protein expression of DNA damage markers, and inflammation increased significantly in the olfactory bulb of older mice. Lower NAD⁺ levels were also detected. Supplementation of NAD⁺ through NR in water improved longevity and partially enhanced olfaction in aged mice. Our studies provide mechanistic and biological insights into the olfaction decline during aging and highlight the role of NAD⁺ for preserving smelling function and general health.     

Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes,associated with cognitive impairment

Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxide (plumbagin) or nitric oxide (NOR-1) to assess the capacity to eliminate them. Under basal conditions, MHE patients show reduced superoxide and peroxynitrite levels and increased nitric oxide (NO) and nitrotyrosine levels. In patients without MHE plumbagin strongly increases cellular superoxide, moderately peroxynitrite and reduces NO levels. In MHE patients, plumbagin increases slightly superoxide and strongly peroxynitrite levels and affects slightly NO levels. NOR-1 increases NO levels much less in patients with than without MHE. These data show that the mechanisms and the capacity to eliminate cellular superoxide, NO and peroxynitrite are enhanced in MHE patients. Superoxide elimination is enhanced through reaction with NO to form peroxynitrite which, in turn, is eliminated by enhanced reaction with biological molecules, which could contribute to cognitive impairment in MHE. The data show that basal free radical levels do not reflect the oxidative stress status in MHE.     

Nitric oxide in hepatic encephalopathy and hyperammonemia

Chronic alcoholism, viral hepatitis or hepatotoxic drug overdose result in liver dysfunction which may lead to a neuropsychiatric disorder termed hepatic encephalopathy (HE). Although, the exact molecular mechanisms underlying the pathophysiology of HE are not known, excitatory/inhibitory neurotransmitter imbalance leading to dysfunction of the glutamate-nitric oxide (NO) system is thought to play a major role. Activation of the NMDA subtype of glutamate receptors leads to increase in intracellular calcium, which initiates several calcium-dependent processes including NO formation. NO is a gaseous, highly reactive, freely diffusible molecule with a short half-life. Recent studies demonstrate increased expression of the neuronal isoform of NO synthase (NOS) and the uptake of L-arginine (the obligate precursor of NO) in both chronic and acute HE. Hyperammonemia associated with liver dysfunction results in increased NO, which may lead to learning and memory impairments and cerebral edema commonly seen, particularly in acute hyperammonemia.     

Machine Learning Classification of Cirrhotic Patients with and without Minimal Hepatic Encephalopathy Based on Regional Homogeneity of Intrinsic Brain Activity

Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.     

Testing for Odor Discrimination and Habituation in Mice

This video demonstrates a technique to establish the presence of a normally functioning olfactory system in a mouse. The test helps determine whether the mouse can discriminate between non-social odors and social odors, whether the mouse habituates to a repeatedly presented odor, and whether the mouse demonstrates dishabituation when presented with a novel odor. Since many social behavior tests measure the experimental animal’s response to a familiar or novel mouse, false positives can be avoided by establishing that the animals can detect and discriminate between social odors. There are similar considerations in learning tests such as fear conditioning that use odor to create a novel environment or olfactory cues as an associative stimulus. Deficits in the olfactory system would impair the ability to distinguish between contexts and to form an association with an olfactory cue during fear conditioning. In the odor habitation/dishabituation test, the mouse is repeatedly presented with several odors. Each odor is presented three times for two minutes. The investigator records the sniffing time directed towards the odor as the measurement of olfactory responsiveness. A typical mouse shows a decrease in response to the odor over repeated presentations (habituation). The experimenter then presents a novel odor that elicits increased sniffing towards the new odor (dishabituation). After repeated presentation of the novel odor the animal again shows habituation. This protocol involves the presentation of water, two or more non-social odors, and two social odors. In addition to reducing experimental confounds, this test can provide information on the function of the olfactory systems of new knockout, knock-in, and conditional knockout mouse lines.     

Winging it: moth flight behavior and responses of olfactory neurons are shaped by pheromone plume dynamics

Terrestrial odor plumes have a physical structure that results from turbulence in the fluid environment. The rapidity of insect flight maneuvers within a plume indicates that their responses are dictated by fleeting (<1 s) rather than longer (>1 s) exposures to odor imposed by physical variables that distribute odor molecules in time and space. Even though encounters with pheromone filaments are brief, male moths responding to female-produced pheromones are remarkably able to extract information relating to the biological properties of these olfactory signals. These properties include the types of molecule present and their relative abundances. Thus, peripheral and central olfactory neurons are capable of representing these biological properties of a pheromone plume within the context of a temporally irregular and unpredictable signal. The mechanisms underlying olfactory processing of these signals with respect to their biological and physical properties are discussed in the context of a behavioral framework.