Olfactory Behavior Research Articles

Functional role of the anterior olfactory nucleus in sensory information processing

Abstract Olfaction, despite being evolutionarily one of the oldest senses, is complex in structure and function. It can distinguish between trillions of odorants, provides orientation, mediates social interactions, and serves as a warning system. Sensory signals from the periphery are first processed in the olfactory bulb (OB) and then distributed to several olfactory cortical structures. Unlike other sensory modalities, this primary sensory information is not relayed via the thalamus. One prominent olfactory cortical region is the anterior olfactory nucleus (AON), a two-layered structure located within the olfactory peduncle. The AON exerts strong reciprocal connections not only to the OB but also to higher brain areas, e.g., the piriform cortex (PCx), thereby serving as a hub for bottom-up and top-down information processing. However, the functional role of the AON is not well-understood. Here, we provide an overview of recent publications investigating the function of AON in olfactory processing and behavior and present a framework for future research on this fascinating archicortical structure.

Using newly optimized genetic tools to probe Strongyloides sensory behaviors

The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and economic burden upon marginalized communities. While current chemotherapies treat strongyloidiasis, disease recrudescence and the looming threat of anthelminthic resistance necessitate novel strategies for nematode control. Throughout its life cycle, S. stercoralis relies upon sensory cues to aid in environmental navigation and coordinate developmental progression. Odorants, tastants, gases, and temperature have been shown to shape parasite behaviors that drive host seeking and infectivity; however, many of these sensory behaviors remain poorly understood, and their underlying molecular and neural mechanisms are largely uncharacterized. Disruption of sensory circuits essential to parasitism presents a promising strategy for future interventions. In this review, we describe our current understanding of sensory behaviors – namely olfactory, gustatory, gas sensing, and thermosensory behaviors – in Strongyloides spp. We also highlight the ever-growing cache of genetic tools optimized for use in Strongyloides that have facilitated these findings, including transgenesis, CRISPR/Cas9-mediated mutagenesis, RNAi, chemogenetic neuronal silencing, and the use of fluorescent biosensors to measure neuronal activity. Bolstered by these tools, we are poised to enter an era of rapid discovery in Strongyloides sensory neurobiology, which has the potential to shape pioneering advances in the prevention and treatment of strongyloidiasis.

Dietary n-3 polyunsaturated fatty acid deficiency alters olfactory mucosa sensitivity in young mice but has no impact on olfactory behavior

ABSTRACT Background and objective We recently showed that perinatal exposure to diets with unbalanced n-6:n-3 polyunsaturated fatty acid (PUFA) ratios affects the olfactory mucosa (OM) fatty acid composition. To assess the repercussions of these modifications, we investigated the impact of diets unbalanced in n-3 PUFAs on the molecular composition and functionality of the OM in young mice. Methods After mating, female mice were fed diets either deficient in α-linolenic acid (LOW diet) or supplemented with n-3 long-chain PUFAs (HIGH diet) during the perinatal period. Weaned male offspring were then fed ad libitum with the same experimental diets for 5 weeks. At 8 weeks of age, olfactory behavior tests were performed in young mice. The fatty acid composition of OM and olfactory cilia, as well as the expression of genes involved in different cellular pathways, were analyzed. The electroolfactograms induced by odorant stimuli were recorded to assess the impact of diets on OM functionality. Results and conclusion Both diets significantly modified the fatty acid profiles of OM and olfactory cilia in young mice. They also induced changes in the expression of genes involved in olfactory signaling and in olfactory neuron maturation. The electroolfactogram amplitudes were reduced in mice fed the LOW diet. Nevertheless, the LOW diet and the HIGH diet did not affect mouse olfactory behavior. Our study demonstrated that consumption of diets deficient in or supplemented with n-3 PUFAs during the perinatal and postweaning periods caused significant changes in young mouse OM. However, these modifications did not impair their olfactory capacities.

Neurotransmitters receptors gene drive the olfactory learning behavior of honeybee

The neurotransmitters receptor gene are multifunctional modulators of behaviors in social insects, with significant effects among species and several dominant roles within the same species. Multiple amines receptors affect diverse behavioral and physiological processes in the honeybee. Apis mellifera ligustica is excellent bee species due to its remarkable learning abilities. Here we analyze whether changes in expression of neurotransmitters receptor genes are related to olfaction learning behavior. We present a behavioral experiment on honeybees’ appetitive olfactory conditioning and examine the relationship between learning success and neurotransmitters receptor gene expression. Bees were trained using proboscis extension response to discriminate learner and failed learner bees and examine the expression of neurotransmitters receptors genes in the brains of learner and failed-learner bees. Real-time quantitative PCR was performed to assess neurotransmitter expression levels. Our finding showed significant results in differentiating the learner and failed-learner bee. The expression level of AmDop1, AmDop2, AmDop3, AmOa1, AmTyr1 and 5-HT showed significantly higher expression in learner and failed-learner bees. Our finding suggests the critical role of neurotransmitters receptors in the olfactory learning behavior of A. mellifera. These significant neurotransmitters receptors could thus act together to define optimal motivational or attentional levels and improve learning success. This study revealed the dynamic modulation of neurotransmitters expression in the brain of learner and failed learner bees and suggested an essential role for neurotransmitters receptors gene in regulating the olfactory learning behavior in honeybees. We suggested that neurotransmitters receptors are expressed in the brain of bees and are likely to be directly influential in regulating olfactory learning success in honeybees.

The Entomopathogenic Fungus Metarhizium anisopliae Affects Feeding Preference of Sogatella furcifera and Its Potential Targets' Identification.

The rice planthopper Sogatella furcifera is a unique vector of the southern rice black-streaked dwarf virus (SRBSDV). The feeding behavior of S. furcifera should directly affect the diffusion of this virus. In this study, we noted that the infection of Metarhizium anisopliae CQMa421 on S. furcifera disturbed the feeding behavior of this pest to SRBSDV-infected rice, from preference to non-preference. Then, we further investigated the potential targets of M. anisopliae CQMa421 on the feeding behavior of S. furcifera after 0 h, 24 h and 48 h of infection by transcriptomic analysis via Illumina deep sequencing. A total of 93.27 GB of data was collected after sequencing, from which 91,125 unigenes were annotated, including 75 newly annotated genes. There were 1380 vs. 2187 and 137 vs. 106 upregulated and downregulated differentially expressed genes (DEGs) detected at 24 h and 48 h, respectively. The biological functions and associated metabolic processes of these genes were determined with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The results suggested that major of DEGs are involved in energy metabolism, biosynthesis, immune response, the FoxO signaling pathway, the MAPK signaling pathway and apoptosis in response to the fungal infection. Noteworthily, several olfactory-related genes, including odorant receptors and odorant binding proteins, were screened from these differentially expressed genes, which played critical roles in regulating the olfactory behavior of insects. Taken together, these results provide new insights for understanding the molecular mechanisms underlying fungus and host insect interaction, especially for olfactory behavior regulated by fungus.

Olfactory Evaluation in Alzheimer's Disease Model Mice.

Olfactory dysfunction is considered a pre-cognitive biomarker of Alzheimer’s disease (AD). Because the olfactory system is highly conserved across species, mouse models corresponding to various AD etiologies have been bred and used in numerous studies on olfactory disorders. The olfactory behavior test is a method required for early olfactory dysfunction detection in AD model mice. Here, we review the olfactory evaluation of AD model mice, focusing on traditional olfactory detection methods, olfactory behavior involving the olfactory cortex, and the results of olfactory behavior in AD model mice, aiming to provide some inspiration for further development of olfactory detection methods in AD model mice.

Cannabinoid Receptor‐Mediated Synaptic Signaling and Neural Plasticity in Central Olfactory Neurons

Our studies aim to understand integrative and computational mechanisms that allow main olfactory bulb neurons to respond to afferent input and synaptic or feedback signals. The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions but our understanding of the role of cannabinoid receptor type 1 (CB1R) in olfactory processing remains limited. Endocannabinoids are known to mediate retrograde signaling at synapses in several brain regions through a form of short‐term neural plasticity. Endocannabinoids are released from depolarized principal neurons and rapidly diffuse to presynaptic inhibitory interneurons to transiently reduce presynaptic firing and neurotransmitter (GABA) release (Depolarization‐Induced Suppression of Inhibition, DSI).We study the function of the endocannabinoid system in regulating neural activity at synapses in the main olfactory bulb, the first central relay station in the brain for the processing of olfactory information coming from the nose. Our experimental approach uses electrophysiological recording techniques, specifically whole cell patch‐clamp recordings. Previously, using anatomical approaches, we showed that CB1R is present in periglomerular processes of a GAD65‐positive population of interneurons but not in mitral cells, key output neurons. We detected eCBs in the mouse main olfactory bulb as well as the expression of CB1R and other genes associated with the cannabinoid signaling system.Output neurons such as mitral cells and tufted cells in the olfactory bulb are computational elements in brain circuits that integrate incoming signals with membrane properties to generate behaviorally relevant synaptic output. Our data support the notion that retrograde signaling is present in neural circuits involving mitral and tufted cells. Mitral and tufted cells release endocannabinoids and, through retrograde signaling, inhibit presynaptic interneurons such as periglomerular cells, which controls the GABA release of these presynaptic neurons. This, in turn, allows mitral and tufted cells to temporarily regulate their synaptic input and relieve them from synaptic inhibition. Endocannabinoids function as retrograde messengers to regulate neural signaling and mediate plasticity at olfactory bulb synapses with potential effects on olfactory threshold and behavior.

Shedding Light on Inter-Individual Variability of Olfactory Circuits in Drosophila.

Inter-individual differences in behavioral responses, anatomy or functional properties of neuronal populations of animals having the same genotype were for a long time disregarded. The majority of behavioral studies were conducted at a group level, and usually the mean behavior of all individuals was considered. Similarly, in neurophysiological studies, data were pooled and normalized from several individuals. This approach is mostly suited to map and characterize stereotyped neuronal properties between individuals, but lacks the ability to depict inter-individual variability regarding neuronal wiring or physiological characteristics. Recent studies have shown that behavioral biases and preferences to olfactory stimuli can vary significantly among individuals of the same genotype. The origin and the benefit of these diverse “personalities” is still unclear and needs to be further investigated. A perspective taken into account the inter-individual differences is needed to explore the cellular mechanisms underlying this phenomenon. This review focuses on olfaction in the vinegar fly Drosophila melanogaster and summarizes previous and recent studies on odor-guided behavior and the underlying olfactory circuits in the light of inter-individual variability. We address the morphological and physiological variabilities present at each layer of the olfactory circuitry and attempt to link them to individual olfactory behavior. Additionally, we discuss the factors that might influence individuality with regard to olfactory perception.

Increases of Phosphorylated Tau (Ser202/Thr205) in the Olfactory Regions Are Associated with Impaired EEG and Olfactory Behavior in Traumatic Brain Injury Mice.

Traumatic brain injury (TBI) leads to long-term cognitive impairments, with an increased risk for neurodegenerative and psychiatric disorders. Among these various impairments, olfactory dysfunction is one of the most common symptoms in TBI patients. However, there are very few studies that show the association between olfactory dysfunction and repetitive TBI. To investigate the effects of repetitive TBI on olfactory functioning and the related pathological neuronal injuries in mice, we applied a weight-drop model of TBI and performed neuropathological examinations and electroencephalography (EEG) in olfactory-bulb-associated areas. Through neuropathological examinations, we found significant increases of amyloid precursor protein (APP) and phosphorylated Tau (p-Tau) (S202/T205) in olfactory-bulb-associated areas. Neuronal atrophy in the lateral anterior olfactory nucleus (AOL), granule layer olfactory bulb (GrO), and dorsal tenia tecta (DTT) was also found to be correlated with p-Tau levels. However, there was no difference in the total Tau levels in the olfactory-bulb-associated areas of TBI mice. Electroencephalography (EEG) of repetitive TBI mouse models showed impaired spontaneous delta oscillation, as well as altered cross-frequency coupling between delta phase and amplitudes of the fast oscillations in the resting-state olfactory bulb. Furthermore, abnormal alterations in EEG band powers were observed during the olfactory oddball paradigm test. TBI also led to impairments of the olfactory-function-associated behaviors. This study provides evidence of behavioral, neuropathological, and physiological alterations in the mouse olfactory system caused by repetitive TBI. Together, p-Tau alterations and EEG impairments may serve as important biomarkers of olfactory-track-associated dysfunctions in repetitive TBI.

Octopaminergic neurons function in appetitive but not aversive olfactory learning and memory in Bactrocera dorsalis.

The biogenic amine octopamine (OA, invertebrate counterpart of noradrenaline) plays critical roles in the regulation of olfactory behavior. Historically, OA has been thought to mediate appetitive but not aversive learning in honeybees, fruit flies (Drosophila), and crickets. However, this viewpoint has recently been challenged because OA activity through a β-adrenergic-like receptor drives both appetitive and aversive learning. Here, we explored the roles of OA neurons in olfactory learning and memory retrieval in Bactrocera dorsalis. We trained flies to associate an orange odor with a sucrose reward or to associate methyl eugenol, a male lure, with N,N-diethyl-3-methyl benzoyl amide (DEET) punishment. We then treated flies with OA receptor antagonists before appetitive or aversive conditioning and a memory retention test. Injection of OA receptor antagonist mianserin or epinastine into the abdomen of flies led to impaired of appetitive learning and memory retention with a sucrose reward, while aversive learning and memory retention with DEET punishment remained intact. Our results suggest that the OA signaling participates in appetitive but not aversive learning and memory retrieval in B. dorsalis through OA receptors.

Low-Level Fluvalinate Treatment in the Larval Stage Induces Impaired Olfactory Associative Behavior of Honey Bee Workers in the Field.

Simple SummaryThere may be high amounts of fluvalinate residue in bee colonies and products. It is usually used to control the varroa parasite on bees, but it may lead to adverse effects on both larvae and adults. In this study, we found that feeding with fluvalinate at a dose of 40 ng/larva could result in declined brood-capping, pupation, and eclosion rates. In addition, the olfactory associative behavior of adult bees was impaired after they were treated with a sublethal dose of 0.004 ng/larva in the larval stage. These findings suggest that a sublethal dose of fluvalinate given to larvae has a huge negative effect on adult honey bee workers, affecting their subsequent associative ability. It may further lead the entire colony to a detrimental developmental trend.Fluvalinate is a widely used insecticide for varroa mite control in apiculture. While most beekeepers have ignored the effects of low levels of fluvalinate on bees, this study aims to demonstrate its effects at very low concentrations. We first used fluvalinate doses ranging from 0.4 to 400 ng/larva to monitor the capping, pupation, and emergence rates of larval bees. Second, we used the honey bees’ proboscis extension reflex reaction to test the learning ability of adult bees that were exposed to fluvalinate doses from 0.004 to 4 ng/larva in the larval stage. The brood-capped rate of larvae decreased dramatically when the dose was increased to 40 ng/larva. Although no significant effect was observed on brood-capping, pupation, and eclosion rates with a dose of 4 ng/larva, we found that the olfactory associative behavior of adult bees was impaired when they were treated with sublethal doses from 0.004 to 4 ng/larva in the larval stage. These findings suggest that a sublethal dose of fluvalinate given to larvae affects the subsequent associative ability of adult honey bee workers. Thus, a very low dose may affect the survival conditions of the entire colony.

Biogenic amines mediate learning success in appetitive odor conditioning in honeybees

ObjectivesBiogenic amines modulate the honeybees' behavioral development, especially olfactory learning behavior. Diverse behavioral protocols have been developed to investigate the olfactory learning behavior of bees to process appetitive olfaction information. Apis mellifera ligustica is a well-known eusocial insect to examine the olfactory learning behavior. This study evaluated the relationship between olfactory learning success and biogenic amines and uncovered the role of biogenic amines to regulate the olfactory learning behavior of bees. MethodsWe used high-performance liquid chromatography (HPLC) with an electrochemical detection (ECD) system to quantify neurotransmitters levels in the bee brain following olfactory learning trials. Furthermore, the bees of the control group and the dopamine flupenthixol blocker injected group were trained to evaluate the olfactory learning performance. ResultsOur finding showed that learning success was directly correlated with the levels of DA and serotonin (5-HT), furthermore, bees of the control group showed higher proboscis extension response than dopamine blocker injected group. Taken together, these findings revealed that dopamine (DA) and serotonin (5-HT) could thus act together to define optimal motivational or attentional levels and improve learning success and indicated that dopamine blocker flupenthixol has to modulate influence on the olfactory learning performance of bees. ConclusionThe results strongly imply that biogenic amines can durably modify the learning behavior in future model insects.

Human odor exploration behavior is influenced by olfactory function and interest in the sense of smell

Olfaction plays an important role in social interaction. This study examined the influence of chemosensory and cognitive abilities on conscious odor sniffing behaviors in humans. Participants (N = 349) were surveyed using a questionnaire for the frequency of behaviors in terms of odor exploration from intrinsic and external sources. Chemosensory functions (e.g., odor identification, trigeminal sensitivity, taste functions, and nasal patency), self-reported olfactory function, and the subjective importance of olfaction were assessed. Hierarchical regression analyses demonstrate a strong impact of olfactory importance on odor exploration behavior. Both female gender and chemosensory function (odor identification ability and trigeminal sensitivity) had a positive impact on odor exploration behavior from individuals' own body and from external sources. Moreover, participants with dysosmia compared to those with normosmia showed less frequent odor exploration behaviors, while their behaviors were partly predicted by nasal patency. In conclusion, conscious olfactory exploration behaviors reflect the interest in the sense of smell and is strongly modulated by chemosensory function. In turn, individuals with lower olfactory sensitivity invest less in olfactory explorations.

Main olfactory bulb reconfiguration by prolonged passive olfactory experience correlates with increased brain‐derived neurotrophic factor and improved innate olfaction

The main olfactory bulb (MOB) is highly plastic and constantly reconfiguring its function and structure depending on sensory experience. Despite the extensive evidence of anatomical, functional and behavioural changes in the olfactory system induced by highly variable olfactory experiences, it is still unknown whether prolonged passive odour experience could reconfigure the MOB at its input and network activity levels and whether these changes impact innate olfaction. Here, by measuring odour-induced glomerular activation, MOB network activity and innate olfactory behaviours, we described a profound MOB reconfiguration induced by prolonged passive olfactory experience in adult animals that impacts MOB input integration at the glomerular layer including an increase in the activated glomerular area and signal intensity, which is combined with a refinement in the number of activated glomeruli and less-overlapped glomerular maps. We also found that prolonged passive olfactory experience dramatically changes MOB population activity in the presence and absence of odours, which is reflected as a decrease in slow oscillations (<12 Hz) and an increase in fast oscillations (>12 Hz). All these functional changes in awake and anaesthetized mice correlate with an increase in brain-derived neurotrophic factor (BDNF) and with improved innate olfactory responses such as habituation/dishabituation and innate preference/avoidance. Our study shows that prolonged passive olfactory experience in adult animals produces a dramatic reconfiguration of the MOB network, possibly driven by BDNF, that improves innate olfactory responses.

Differential gene expression analysis following olfactory learning in honeybee (Apis mellifera L.).

Insects change their stimulus-response through the perception of associating these stimuli with important survival events such as rewards, threats, and mates. Insects develop strong associations and relate them to their experiences through several behavioral procedures. Among the insects, Apis species, Apis mellifera ligustica are known for their outstanding ability to learn with tremendous economic importance. Apis mellifera ligustica has a strong cognitive ability and promising model species for investigating the neurobiological basis of remarkable olfactory learning abilities. Here we evaluated the olfactory learning ability of A. mellifera by using the proboscis extension reflex (PER) protocol. The brains of the learner and failed-learner bees were examined for comparative transcriptome analysis by RNA-Seq to explain the difference in the learning capacity. In this study, we used an appetitive olfactory learning paradigm in the same age of A. mellifera bees to examine the differential gene expression in the brain of the learner and failed-learner. Bees that respond in 2nd and 3rd trials or only responded to 3rd trials were defined as learned bees, failed-learner individuals were those bees that did not respond in all learning trials The results indicate that the learning ability of learner bees was significantly higher than failed-learner bees for 12 days. We obtained approximately 46.7 and 46.4 million clean reads from the learner bees failed-learner bees, respectively. Gene expression profile between learners’ bees and failed-learners bees identified 74 differentially expressed genes, 57 genes up-regulated in the brains of learners and 17 genes were down-regulated in the brains of the bees that fail to learn. The qRT-PCR validated the differently expressed genes. Transcriptome analyses revealed that specific genes in learner and failed-learner bees either down-regulated or up-regulated play a crucial role in brain development and learning behavior. Our finding suggests that down-regulated genes of the brain involved in the integumentary system, storage proteins, brain development, sensory processing, and neurodegenerative disorder may result in reduced olfactory discrimination and olfactory sensitivity in failed-learner bees. This study aims to contribute to a better understanding of the olfactory learning behavior and gene expression information, which opens the door for understanding of the molecular mechanism of olfactory learning behavior in honeybees.

Screening of olfactory genes related to blood-feeding behaviors in Culex pipiens quinquefasciatus and Culex pipiens molestus by transcriptome analysis.

BackgroundCulex pipiens quinquefasciatus Say (Cx. quinquefasciatus) and Culex pipiens form molestus Forskal (Cx. molestus) in the Culex pipiens complex group show considerable differences in host seeking, blood feeding, mating behavior and in vector competence. Blood-feeding mosquito behaviors are closely related to their olfactory gene expression and olfactory gene repertoire composition. Comparing olfactory genes between these two subspecies with significantly different blood-feeding behaviors can support further research on the molecular mechanism of the Culex pipiens complex olfactory sensory system, providing a new approach for determining candidate attractant or repellent compounds.MethodsNon-blood-feeding (NBF) and post-blood-feeding (PBF) olfactory system transcriptomes of the two subspecies were sequenced, and the biological functions of their differentially expressed genes were described by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was applied to validate the RNA-seq data. The roles of particular olfactory receptors in Cx. quinquefasciatus blood-feeding behaviors were evaluated by RNAi.ResultsFive, 7, 24, and 3 Cx. quinquefasciatus-specific OBPs, Cx. molestus-specific OBPs, Cx. quinquefasciatus-specific ORs and Cx. molestus-specific ORs were identified, respectively. The majority of selected ORs were consistent with the predicted transcriptome sequencing results after qRT-PCR validation. OR5 was expressed only in Cx. quinquefasciatus, and OR65 was the only gene upregulated after blood feeding in Cx. molestus. The blood-feeding rates of the OR5 and OR78 dsRNA groups were significantly lower (4.3%±3.1% and 13.3%±11.5%) than those of the enhanced green fluorescence protein (EGFP) group (64.5%±8.7%).ConclusionMost OBPs and ORs were expressed in both subspecies but showed divergence in expression level. OR5 and OR65 might be species-specific expressed genes that regulate the olfactory behaviors of Cx. quinquefasciatus and Cx. molestus, respectively. The RNA interference of OR5 and OR78 could inhibit the blood-feeding behavior of Cx. quinquefasciatus, providing new targets for screening effective repellent compounds to control mosquito-borne diseases effectively and efficiently.

Artificial Selection Drives SNPs of Olfactory Receptor Genes into Different Working Traits in Labrador Retrievers.

Labs as guide dogs or sniffer dogs in usage have been introduced into China for more than 20 years. These two types of working dogs own blunt or acute olfactory senses, which have been obtained by artificial selection in relatively closed populations. In order to attain stable olfactory attributes and meet use-oriented demands, Chinese breeders keep doing the same artificial selection. Though olfactory behavior is canine genetic behavior, genotypes of OR genes formed by breeding schemes are largely unknown. Here, we characterized 26 SNPs, 2 deletions, and 2 insertions of 7 OR genes between sniffer dogs and guide dogs in order to find out the candidate alleles associated with working specific traits. The results showed that there were candidate functional SNP alleles in one locus that had statistically severely significant differences between the two subpopulations. Furthermore, the levels of polymorphism were not high in all loci and linkage disequilibrium only happened within one OR gene. Hardy–Weinberg equilibrium (HWE) tests showed that there was a higher ratio not in HWE and lower FST within the two working dog populations. We conclude that artificial selection in working capacities has acted on SNP alleles of OR genes in a dog breed and driven the evolution in compliance with people's intentions though the changes are limited in decades of strategic breeding.

VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination.

In the olfactory bulb (OB), olfactory information represented by mitral/tufted cells (M/Ts) is extensively modulated by local inhibitory interneurons before being transmitted to the olfactory cortex. While the crucial roles of cortical vasoactive-intestinal-peptide-expressing (VIP) interneurons have been extensively studied, their precise function in the OB remains elusive. Here, we identify the synaptic connectivity of VIP interneurons onto mitral cells (MCs) and demonstrate their important role in olfactory behaviors. Optogenetic activation of VIP interneurons reduced both spontaneous and odor-evoked activity of M/Ts in awake mice. Whole-cell recordings revealed that VIP interneurons decrease MC firing through direct inhibitory synaptic connections with MCs. Furthermore, inactivation of VIP interneurons leads to increased MC firing and impaired olfactory detection and odor discrimination. Therefore, our results demonstrate that VIP interneurons control OB output and play critical roles in odor processing and olfactory behaviors.

Prenatal Hypoxia Impairs Olfactory Function in Postnatal Ontogeny in Rats.

Analysis of the age-related dynamics of olfactory behavior in the odor preference and food search testsshowed that all male Wistar rats, regardless of age, preferred valerian essential oil, whose components have the properties of pheromones in rodents, when given a selection of eight essential oils; young rats displayed better food-seeking results than adult and old animals. Acute prenatal hypoxia (PH) on E14 (7% O2 for 3 h) led to impairment of the valerian odor preference at all ages studied and to decreased productivity of food searches. Neurodegenerative processes were seen in the piriform cortex after PH, with reductions in the number of neurons and increases in glial elements. We have previously observed these changes in the entorhinal cortex and hippocampus, but not in the olfactory bulbs. This suggests that PH-induced decreases in olfactory function in rats may result from impairments to the formation of the central elements of the analyzer during the first months of postnatal ontogeny.

Ablation of microRNAs in VIP+ interneurons impairs olfactory discrimination and decreases neural activity in the olfactory bulb.

MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP+ ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP+ interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP+ miRNA affects olfactory function and neural activity in olfactory centres such as the olfactory bulb, which contains a large number of VIP+ interneurons. A go/no-go odour discrimination task and a food-seeking test were used to assess olfactory discrimination and olfactory detection. In vivo electrophysiological techniques were used to record single units and local field potentials. Olfactory detection and olfactory discrimination behaviours were impaired in VIP+ -specific Dicer-knockout mice. In vivo electrophysiological recordings in awake, head-fixed mice showed that both spontaneous and odour-evoked firing rates were decreased in mitral/tufted cells in knockout mice. The power of ongoing and odour-evoked beta local field potentials response of the olfactory bulb and anterior piriform cortex were dramatically decreased. Furthermore, the coherence of theta oscillations between the olfactory bulb and anterior piriform cortex was decreased. Importantly, Dicer knockout restricted to olfactory bulb VIP+ interneurons recapitulated the behavioural and electrophysiological results of the global knockout. VIP+ miRNAs are an important factor in sensory processing, affecting olfactory function and olfactory neural activity.