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Olfactory dysfunction is manifested in a wide range of neurological and psychiatric diseases, and often emerges prior to the onset of more classical symptoms and signs. From a behavioral perspective, olfactory deficits typically arise in conjunction with impairments of cognition, motivation, memory, and emotion. However, a conceptual framework for explaining the impact of olfactory processing on higher brain functions in health and disease remains lacking. Here we aim to provide circuit-level insights into this question by synthesizing recent advances in olfactory network connectivity with other cortical brain regions such as the prefrontal cortex. We will focus on social cognition as a representative model for exploring and critically evaluating the relationship between olfactory cortices and higher-order cortical regions in rodent models. Although rodents do not recapitulate all dimensions of human social cognition, they have experimentally accessible neural circuits and well-established behavioral tests for social motivation, memory/recognition, and hierarchy, which can be extrapolated to other species including humans. In particular, the medial prefrontal cortex (mPFC) has been recognized as a key brain region in mediating social cognition in both rodents and humans. This review will highlight the underappreciated connectivity, both anatomical and functional, between the olfactory system and mPFC circuitry, which together provide a neural substrate for olfactory modulation of social cognition and social behaviors. We will provide future perspectives on the functional investigation of the olfactory-mPFC circuit in rodent models and discuss how to translate such animal research to human studies.

The primary olfactory centres of metazoans as diverse as arthropods and mammals consist of an array of fields of dense synaptic neuropil, the olfactory glomeruli. However, the neurochemical structure of crustacean olfactory glomeruli is largely understudied when compared to the insects. We analysed the glomerular architecture in selected species of hermit crabs using immunohistochemistry against presynaptic proteins, the neuropeptides orcokinin, RFamide and allatostatin, and the biogenic amine serotonin. Our study reveals an unexpected level of structural complexity, unmatched by what is found in the insect olfactory glomeruli. Peptidergic and aminergic interneurons provide the structural basis for a regionalization of the crustacean glomeruli into longitudinal and concentric compartments. Our data suggest that local olfactory interneurons take a central computational role in modulating the information transfer from olfactory sensory neurons to projection neurons within the glomeruli. Furthermore, we found yet unknown neuronal elements mediating lateral inhibitory interactions across the glomerular array that may play a central role in modulating the transfer of sensory input to the output neurons through presynaptic inhibition. Our study is another step in understanding the function of crustacean olfactory glomeruli as highly complex units of local olfactory processing. This article is protected by copyright. All rights reserved.

Key points Obesity can disrupt the structure and function of organ systems, including the olfactory system that is important for food selection and satiety. We designed dietary treatments in mice such that mice received fat, but the total calories provided were the same as in control diets so that they would not gain weight or increase adipose tissue. Mice that were not obese but consumed isocaloric fatty diets still lost olfactory neuronal circuits, had fewer numbers of olfactory neurons, had an elevation in inflammatory signals, and an intermediate ability to clear glucose (prediabetes). Mice were allowed access to running wheels while consuming fatty diets, yet still lost olfactory structures. We conclude that a long-term imbalance in nutrition that favors fat in the diet disrupts the olfactory system of mice in the absence of obesity. Abstract Excess nutrition causes loss of olfactory sensory neurons (OSNs) and reduces odor discrimination and odor perception in mice. To separate diet-induced obesity from the consumption of dietary fat, we designed pair-feeding experiments whereby mice were maintained on isocaloric diets for 5 months that prevented increased fat storage. To test our hypothesis that adiposity was not a prerequisite for loss of OSNs and bulbar projections, we used male and female mice with an odorant receptor-linked genetic reporter (M72tauLacZ; Olfr160) to visualize neural circuitry changes resulting from fat in the diet. Simultaneously we monitored glucose clearance (diagnostic for prediabetes), body fat deposition, ingestive behaviors, select inflammatory markers, and energy metabolism. Axonal projections to defined olfactory glomeruli were visualized in whole-mount brains and the number of OSNs were manually counted across whole olfactory epithelia. After being pair fed a moderately high-fat (MHF) diet, mice of both sexes had body weight, adipose deposits, energy expenditure, respiratory exchange ratios, and locomotor activity that were unchanged from control-fed mice. Despite this, they were still found to lose OSNs and associated bulbar projections. Even with unchanged adipocyte storage, pair-fed animals had an elevation in TNF cytokines and an intermediate ability for glucose clearance. Albeit improving health metrics, access to voluntary running while consuming an ad libitum fatty diet, still precipitated a loss of OSNs and associated axonal projections for male mice. Our results support that long-term macronutrient imbalance can drive anatomical loss in the olfactory system regardless of total energy expenditure. This article is protected by copyright. All rights reserved.

The author previously worked extensively on the broad problem of the evolution of the vertebrate pallium. He proposed various Bauplan models covering at least gnathostomes, based in the definition of a set of pallial sectors with topologically invariant positional relationships and distinct molecular profiles. Out of one of these models, presented as the “updated tetrapartite pallium model,” a modified definition of the earlier lateral pallium sector (LPall) concept emerged, characterizing it in mammals as an unitary claustro-insular transitional (mesocortical) complex intercalated between the neocortex or dorsal pallium (DPall) above and olfactory cortex or ventral pallium (VPall) underneath. A distinctive molecular marker of the early-born deep claustral component of the LPall was found to be the transcription factor Nr4a2, which is not expressed significantly in the overlying insular cortex or in adjoining cortical territories. Given that earlier comparative studies had identified molecularly and topologically comparable VPall, LPall, and DPall sectors in the avian pallium, an avian Nr4a2 probe was applied, aiming to identify the reportedly absent avian claustro-insular complex. An early-born superficial subpopulation of the avian LPall that expresses this marker selectively through development was indeed found. This was proposed to be a claustrum homolog, whereas the remaining Nr4a2-negative avian LPall cells were assumed to represent a possible insular homolog. This last notion was subsequently supported by comparable selective expression of the mouse insular marker Cyp26b, also found restricted to the avian LPall. Some published data suggested that similar molecular properties and structure apply at the reptilian LPall. This analysis was reviewed in Puelles et al. [The pallium in reptiles and birds in the light of the updated tetrapartite pallium model. 2017]. Four years on, the present commentary discusses some international publications accrued in the interval that touch on the claustro-insular homology hypothesis. Some of them are opposed to the hypothesis whereas others corroborate or support it. This raises a number of secondary issues of general interest.

Olfactory input into the brain can be disrupted by a variety of environmental factors, including exposure to pathogens or environmental contaminants. Olfactory cues are often eliminated in laboratory rats and mice through highly invasive procedures like olfactory bulbectomy, which may also disrupt accessory olfactory pathways and detection of non-volatile odors. In the present study, we tested whether inducing anosmia through intranasal infusion of zinc gluconate alters aggression in a monogamous, biparental rodent species, the California mouse (Peromyscus californicus). This less invasive method of manipulating olfaction selectively targets the olfactory epithelium and reduces the detection of volatile odors. Treatment with zinc gluconate extended the time required for male and female California mice to find hidden pieces of apple and reduced the amount of time spent investigating bedding that was soiled by unfamiliar males. Moreover, inhibition of olfaction with zinc gluconate reduced aggressiveness in both sexes as demonstrated by an increased attack latency in the resident-intruder test among same-sex dyads from the same treatment group. These results suggest that volatile olfactory cues are necessary for agonistic responses in both male and female California mice. Therefore, even in species with complex social systems that include territorial aggression and monogamy, volatile olfactory cues modulate agonistic behavior.

The olfactory system allows animals to navigate in their environment to feed, mate, and escape predators. It is well established that odorant exposure or electrical stimulation of the olfactory system induces stereotyped motor responses in fishes. However, the neural circuitry responsible for the olfactomotor transformations is only beginning to be unraveled. A neural substrate eliciting motor responses to olfactory inputs was identified in the lamprey, a basal vertebrate used extensively to examine the neural mechanisms underlying sensorimotor transformations. Two pathways were discovered from the olfactory organ in the periphery to the brainstem motor nuclei responsible for controlling swimming. The first pathway originates from sensory neurons located in the accessory olfactory organ and reaches a single population of projection neurons in the medial olfactory bulb, which, in turn, transmit the olfactory signals to the posterior tuberculum and then to downstream brainstem locomotor centers. A second pathway originates from the main olfactory epithelium and reaches the main olfactory bulb, the neurons of which project to the pallium/cortex. The olfactory signals are then conveyed to the posterior tuberculum and then to brainstem locomotor centers. Olfactomotor behavior can adapt, and studies were aimed at defining the underlying neural mechanisms. Modulation of bulbar neural activity by GABAergic, dopaminergic, and serotoninergic inputs is likely to provide strong control over the hardwired circuits to produce appropriate motor behavior in response to olfactory cues. This review summarizes current knowledge relative to the neural circuitry producing olfactomotor behavior in lampreys and their modulatory mechanisms.

In sub-mammalian vertebrates like fishes, amphibians, and reptiles, new neurons are produced during the entire lifespan. This capacity diminishes considerably in birds and even more in mammals where it persists only in the olfactory system and hippocampal dentate gyrus. Adult neurogenesis declines even more drastically in nonhuman primates and recent evidence shows that this is basically extinct in humans. Why should such seemingly useful capacity diminish during primate evolution? It has been proposed that this occurs because of the need to retain acquired complex knowledge in stable populations of neurons and their synaptic connections during many decades of human life. In this review, we will assess critically the claim of significant adult neurogenesis in humans and show how current evidence strongly indicates that humans lack this trait. In addition, we will discuss the allegation of many rodent studies that adult neurogenesis is involved in psychiatric diseases and that it is a potential mechanism for human neuron replacement and regeneration. We argue that these reports, which usually neglect significant structural and functional species-specific differences, mislead the general population into believing that there might be a cure for a variety of neuropsychiatric diseases as well as stroke and brain trauma by genesis of new neurons and their incorporation into existing synaptic circuitry.

Olfactory dysfunction is observed in several neurological disorders including Mild Cognitive Impairment (MCI) and Alzheimer disease (AD). These deficits occur early and correlate with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite extensive human studies, there has been little characterization of the olfactory system in models of AD. In order to determine if olfactory structural and/or molecular phenotypes are observed in a model expressing a genetic risk factor for AD, we assessed the olfactory bulb (OB) in APOE4 transgenic mice. A significant decrease in OB weight was observed at 12 months of age in APOE4 mice concurrent with inflammation and decreased NeuN expression. In order to determine if a diet rich in omega-3s may alleviate the olfactory system phenotypes observed, we assessed WT and APOE4 mice on a docosahexaenoic acid (DHA) diet. APOE4 mice on a DHA diet did not present with atrophy of the OB, and the alterations in NeuN and IBA-1 expression were alleviated. Furthermore, alterations in caspase mRNA and protein expression in the APOE4 OB were not observed with a DHA diet. Similar to the human AD condition, OB atrophy is an early phenotype in the APOE4 mice and concurrent with inflammation. These data support a link between the structural olfactory brain region atrophy and the olfactory dysfunction observed in AD and suggest that inflammation and cell death pathways may contribute to the olfactory deficits observed. Furthermore, the results suggest that diets enriched in DHA may provide benefit to APOE4 allele carriers.

Sensory information, sampled by sensory organs positioned on each side of the body may play a crucial role in organizing brain lateralization. This question is of particular interest with regard to the growing evidence of alteration in lateralization in several psychiatric conditions. In this context, the olfactory system, an ancient, mostly ipsilateral and well-conserved system across phylogeny may prove an interesting model system to understand the behavioral significance of brain lateralization. Here, we focused on behavioral data in vertebrates and non-vertebrates, suggesting that the two hemispheres of the brain differentially processed olfactory cues to achieve diverse sensory operations, such as detection, discrimination, identification of behavioral valuable cues or learning. These include reports across different species on best performances with one nostril or the other or odorant active sampling by one nostril or the other, depending on odorants or contexts. In some species, hints from peripheral anatomical or functional asymmetry were proposed to explain these asymmetries in behavior. Instigations of brain activation or more rarely of brain connectivity evoked by odorants revealed a complex picture with regards to asymmetric patterns which is discussed with respect to behavioral data. Along the steps of the discussed literature, we propose avenues for future research.

Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that the induction of a CYP gene by an odorant does not necessarily indicate a role for that CYP in neuronal responses to that odorant. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.

The development of precise neural circuits is initially directed by genetic programming and subsequently refined by neural activity. In the mouse olfactory system, axons from various olfactory sensory neurons expressing the same olfactory receptor converge onto a few spatially invariant glomeruli, generating the olfactory glomerular map in the olfactory bulbs. Using the glomerular map formation as a model, this review summarizes the current understanding of mechanisms underlying topographic map development in the mouse olfactory system and highlights how neural activity instructs the map refinement process.

Virgin female laboratory mice readily express pup care when co-housed with dams and pups. However, pup-sensitized virgins fail to express intruder-directed aggression on a single session of testing. To study whether repeated testing would affect the onset and dynamics of maternal or intruder-directed aggression, we tested dams and their accompanying virgins from postpartum day 4 to 6. Repeated testing led to escalated aggression towards male intruders in dams, but virgins never developed aggression. In dams, inhibition of the medial amygdala using DREADD (designer receptors exclusively activated by designer drugs) vectors carrying the hM4Di receptor blocked the expected increase in maternal aggression on the second testing day. Our data support that the onset of maternal aggression is linked to physiological changes occurring during motherhood, and that medial amygdala, a key centre integrating vomeronasal, olfactory and hormonal information, enables the expression of escalated aggression induced by repeated testing. Future studies selectively targeting specific neuronal populations of the medial amygdala are needed to allow a deeper understanding of the control of experience-dependent aggression increase, a phenomenon leading to the high aggression levels found in violent behaviours.

How an organism's sensory system functions is central to how it navigates its environment. The insect olfactory system is a prominent model for investigating how ecological factors impact sensory reception and processing. Notably, work in Lepidoptera led to the discovery of vastly expanded structures, termed macroglomerular complexes (MGCs), within the primary olfactory processing centre. MGCs typically process pheromonal cues, are usually larger in males, and provide classic examples of how variation in the size of neural structures reflects the importance of sensory cues. Though prevalent across moths, MGCs were lost during the origin of butterflies, consistent with evidence that courtship initiation in butterflies is primarily reliant on visual cues, rather than long distance chemical signals. However, an MGC was recently described in a species of ithomiine butterfly, suggesting that this once lost neural adaptation has re-emerged in this tribe. Here, we show that MGC-like morphologies are widely distributed across ithomiines, but vary in both their structure and prevalence of sexual dimorphism. Based on this interspecific variation we suggest that the ithomiine MGC is involved in processing both plant and pheromonal cues, which have similarities in their chemical constitution, and co-evolved with an increased importance of plant derived chemical compounds., NERC IRF; Royal Society Research Grant; Royal Commission for the Great Exhibition Research Fellowship

In sensory systems of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at various stages in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, Cre-driver lines that distinguish them do not yet exist. Here, we sought to identify genes that are differentially expressed between MCs and TCs of the mouse, with an ultimate goal to generate a cell-type specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Many genes were differentially expressed, but only a few showed consistent expressions in MCs and at the specificity required. After further validating these putative markers using in-situ hybridization, two genes, namely Pkib and Lbdh2, remained as promising candidates. Using CRISPR/Cas9-mediated gene editing, we generated Cre-driver lines and analysed the resulting recombination patterns. This indicated that our new inducible Cre-driver line, Lbhd2-CreERT2, can be used to genetically label MCs in a tamoxifen dose-dependent manner, both in male and female mice, as assessed by soma locations, projection patterns and sensory-evoked responses in vivo. Hence this is a promising tool for investigating cell-type specific contributions to olfactory processing and demonstrates the power of publicly accessible data in accelerating science. SIGNIFICANCE STATEMENT: In the brain, distinct cell types play unique roles. It is therefore important to have tools for studying unique cell types specifically. For the sense of smell in mammals, information is processed first by circuits of the olfactory bulb, where two types of cells, mitral cells and tufted cells, output different information. We generated a transgenic mouse line that enables mitral cells to be specifically labelled or manipulated. This was achieved by looking for genes that are specific to mitral cells using a large and public gene expression dataset, and creating a transgenic mouse using the gene editing technique, CRISPR/Cas9. This will allow scientists to better investigate parallel information processing underlying the sense of smell.

Background: Deficits in odor detection and discrimination are premature symptoms of Alzheimer’s disease (AD) that correlate with pathological signs in the olfactory bulb (OB) and piriform cortex (PCx). Similar olfactory dysfunction has been characterized in AD transgenic mice that overproduce amyloid-β peptide (Aβ), which can be prevented by reducing Aβ levels by immunological and pharmacological means, suggesting that olfactory dysfunction depends on Aβ accumulation and Aβ-driven alterations in the OB and/or PCx, as well as on their activation. However, this possibility needs further exploration. Objective: To characterize the effects of Aβ on OB and PCx excitability/coupling and on olfaction. Methods: Aβ oligomerized solution (containing oligomers, monomers, and protofibrils) or its vehicle were intracerebroventricularlly injected two weeks before OB and PCx excitability and synchrony were evaluated through field recordings in vivo and in brain slices. Synaptic transmission from the OB to the PCx was also evaluated in slices. Olfaction was assessed through the habituation/dishabituation test. Results: Aβ did not affect lateral olfactory tract transmission into the PCx but reduced odor habituation and cross-habituation. This olfactory dysfunction was related to a reduction of PCx and OB network activity power in vivo. Moreover, the coherence between PCx-OB activities was also reduced by Aβ. Finally, Aβ treatment exacerbated the 4-aminopyridine-induced excitation in the PCx in slices. Conclusion: Our results show that Aβ-induced olfactory dysfunction involves a complex set of pathological changes at different levels of the olfactory pathway including alterations in PCx excitability and its coupling with the OB. These pathological changes might contribute to hyposmia in AD.

Sociality is classified as one of the major transitions in evolution, with the largest number of eusocial species found in the insect order Hymenoptera, including the Apini (honey bees) and the Bombini (bumble bees). Bumble bees and honey bees not only differ in their social organization and foraging strategies, but comparative analyses of their genomes demonstrated that bumble bees have a slightly less diverse family of olfactory receptors than honey bees, suggesting that their olfactory abilities have adapted to different social and/or ecological conditions. However, unfortunately, no precise comparison of olfactory coding has been performed so far between honey bees and bumble bees, and little is known about the rules underlying olfactory coding in the bumble bee brain. In this study, we used in vivo calcium imaging to study olfactory coding of a panel of floral odorants in the antennal lobe of the bumble bee Bombus terrestris. Our results show that odorants induce reproducible neuronal activity in the bumble bee antennal lobe. Each odorant evokes a different glomerular activity pattern revealing this molecule’s chemical structure, i.e. its carbon chain length and functional group. In addition, pairwise similarity among odor representations are conserved in bumble bees and honey bees. This study thus suggests that bumble bees, like honey bees, are equipped to respond to odorants according to their chemical features.

Insects possess a fairly sophisticated olfactory system in their antennae to detect odorants essential for their survival and reproduction. Among them, insect first perceives odour sources by odorant-binding proteins (OBPs) to locate host-plants. Methyl salicylate, (Z)-3-hexenyl acetate and dibutyl phthalate are major volatile components of Ulmus pumila and Ricinus communis and elicit strong responses of the scarab beetle Holotrichia oblita adults. However, olfactory perception of the scarab beetle to these odorant compounds is unclear. In the current study, we cloned the OBP6 and OBP7 of H. oblita. The expression pattern shows that the two genes were highly expressed in the antennae of female beetles. Binding assays verified that the HoblOBP6 had a better binding affinity to methyl salicylate, and so did HoblOBP7 to (Z)-3-hexenyl acetate and dibutyl phthalate. The effect on the responses of female beetles to the three compounds was decreased significantly after these two genes were silenced by RNA interference. These results indicate that HoblOBP6 and HoblOBP7 are essential for female H. oblita perception of methyl salicylate, (Z)-3-hexenyl acetate and dibutyl phthalate. Our study provides important insights into the olfactory mechanism of female H. oblita to ester plant volatiles and could facilitate the development of potential pest control strategies in the field.

Activating transcription factor 5 (ATF5) is a stress-responsive transcription factor that belongs to the cAMP response element-binding protein (CREB)/ATF family, and is essential for the differentiation and survival of sensory neurons in murine olfactory organs. However, the study of associated proteins and target genes for ATF5 has been hampered due to the limited availability of immunoprecipitation-grade ATF5 antibodies. To overcome this issue, we generated hemagglutinin (HA)-tag knock-in mice for ATF5 using CRISPR/Cas9-mediated genome editing with one-step electroporation in oviducts (i-GONAD). ATF5-HA fusion proteins were detected in the nuclei of immature and some mature olfactory and vomeronasal sensory neurons in the main olfactory epithelium and vomeronasal organ, respectively, as endogenous ATF5 proteins were expressed, and some ATF5-HA proteins were found to be phosphorylated. Chromatin immunoprecipitation (ChIP) experiments revealed that ATF5-HA bound to the CCAAT/enhancer-binding protein (C/EBP)-ATF response element site in the promotor region of receptor transporting protein 1 (Rtp1), a chaperone gene responsible for proper olfactory receptor expression. These knock-in mice may be used to examine the expression, localization, and protein-protein/-DNA interactions of endogenous ATF5 and, ultimately, the function of ATF5 in vivo.

BACKGROUND: Odorant‐binding proteins (OBPs) in insects contribute to the sensitivity of the olfactory system and connect external odorants to olfactory receptor neurons. Determination of the chemosensory functions in Diaphorina citri, a vector of the citrus Huanglongbing pathogen, may help in developing a potential target for pest management. RESULTS: Diaphorina citri showed dose‐dependent electroantennogram recording (EAG) responses to 12 host plant volatiles. A two‐choice behavioral trap experiment showed that four compounds (methyl salicylate, linalool, citral and R‐(+)‐limonene) that elicited high EAG responses also had significant attraction to adults. The expression profiles induced by these compounds were detected in nine OBP genes, DcitOBP1–9. DcitOBP3, DcitOBP6 and DcitOBP7 commonly showed significant upregulation or downregulation compared with the control. Microscale thermophoresis (MST) showed that the recombinant protein DcitOBP7 had high in vitro binding affinities (Kd

The vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after birth. The vomeronasal epithelium (VNE) of rodents is composed of two major types of vomeronasal sensory neurons (VSNs): (1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gαi2, and (2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Gαo. Recent studies identified a third subclass of Gαi2 and Gαo VSNs that express the formyl peptide receptor family. VSNs expressing V1Rs or V2Rs send their axons to distinct regions of the accessory olfactory bulb (AOB). Together, VNO and AOB form the accessory olfactory system (AOS), an olfactory subsystem that coordinates the social and sexual behaviors of many vertebrate species. In this review, we summarize our current understanding of cellular and molecular mechanisms that underlie VNO development. We also discuss open questions for study, which we suggest will further enhance our understanding of VNO morphogenesis at embryonic and postnatal stages.

Olfactory receptor families have arisen independently several times during evolution. The origin of taar genes, one of the four major vertebrate olfactory receptor families, is disputed. We performed a phylogenetic analysis making use of 96 recently available genomes, and report that olfactory functionality has arisen twice independently within the TAAR family, once in jawed and once in jawless fish. In lamprey, an ancestral gene expanded to generate a large family of olfactory receptors, while the sister gene in jawed vertebrates did not expand and is not expressed in olfactory sensory neurons. Both clades do not exhibit the defining TAAR motif, and we suggest naming them taar-like receptors (tarl). We have identified the evolutionary origin of both taar and tarl genes in a duplication of the serotonergic receptor 4 that occurred in the most recent common ancestor of vertebrates. We infer two ancestral genes in bony fish (TAAR12, TAAR13) which gave rise to the complete repertoire of mammalian olfactory taar genes and to class II of the taar repertoire of teleost fish. We follow their evolution in seventy-one bony fish genomes and report a high evolutionary dynamic, with many late gene birth events and both early and late gene death events.

The crustacean first antenna, or antennule, has been an experimental model for studying sensory biology for over 150 years. Investigations have led to a clearer understanding of the functional organization of the antennule as an olfactory organ but also to a realization that the antennule is much more than that. Across the Crustacea, the antennules take on many forms and functions. As an example, the antennule of reptantian decapods has many types of sensilla, each with distinct structure and function and with hundreds of thousands of chemosensory neurons expressing hundreds of genes that code for diverse classes of receptor proteins. Together, these antennular sensilla represent multiple chemosensory pathways, each with its own central connections and functions. The antennule also has a diversity of sensors of mechanical stimuli, including vibrations, touch, water flow, and the animal's own movements. The antennule likely also detects other environmental cues, such as temperature, oxygen, pH, salinity, and noxious stimuli. Furthermore, the antennule is a motor organ-it is flicked to temporally and spatially sample the animal's chemo-mechanical surroundings-and this information is used in resolving the structure of chemical plumes and locating the odor source. The antennule is also adapted to maintain lifelong function in a changing environment. For example, it has specific secretory glands, grooming structures, and behaviors to stay clean and functional. Antennular sensilla and the annuli on which they reside are also added and replaced, leading to a complete turnover of the antennule over several molts. Thus, the antennule is a complex and dynamic sensory-motor integrator that is intricately engaged in most aspects of the lives of crustaceans.

Individual olfactory sensory neurons (OSNs) in the mouse main olfactory epithelium express a single odorant receptor (OR) gene from the repertoire of either class I or class II ORs. The transcription factor Bcl11b determines the OR class to be expressed in OSNs. The septal organ (SO), a small neuroepithelium located at the ventral base of the nasal septum, is considered as an olfactory subsystem because it expresses a specific subset of ORs. However, the mechanisms underlying the generation and differentiation of SO-OSN remain unknown. In the present study, we show that the generation and differentiation of SO-OSN employ the same genetic pathway as in the OSN lineage, which is initiated by the neuronal fate determinant factor Ascl1. Additionally, the key role of Bcl11b in the SO is demonstrated by the abnormal phenotypes of Bcl11b-deficient mice: significant reduction in the expression of OR genes and in the number of mature SO-OSNs. Although SO-OSNs are specified to express a subset of class II OR genes in wild-type mice, the Bcl11b deletion led to the expression of class I OR genes, while the expression of class II OR genes was significantly decreased, with one exception of Olfr15. These results indicate that Bcl11b is necessary for proper OR expression in SO-OSNs.

Homeostatic matching of pre- and postsynaptic function has been observed in many species and neural structures, but whether transcriptional changes contribute to this form of trans-synaptic coordination remains unknown. To identify genes whose expression is altered in presynaptic neurons as a result of perturbing postsynaptic excitability, we applied a transcriptomics-friendly, temperature-inducible Kir2.1-based activity clamp at the first synaptic relay of theDrosophilaolfactory system, a central synapse known to exhibit trans-synaptic homeostatic matching. Twelve hours after adult-onset suppression of activity in postsynaptic antennal lobe projection neurons of males and females, we detected changes in the expression of many genes in the third antennal segment, which houses the somata of presynaptic olfactory receptor neurons. These changes affected genes with roles in synaptic vesicle release and synaptic remodeling, including several implicated in homeostatic plasticity at the neuromuscular junction. At 48 h and beyond, the transcriptional landscape tilted toward protein synthesis, folding, and degradation; energy metabolism; and cellular stress defenses, indicating that the system had been pushed to its homeostatic limits. Our analysis suggests that similar homeostatic machinery operates at peripheral and central synapses and identifies many of its components. The presynaptic transcriptional response to genetically targeted postsynaptic perturbations could be exploited for the construction of novel connectivity tracing tools.SIGNIFICANCE STATEMENTHomeostatic feedback mechanisms adjust intrinsic and synaptic properties of neurons to keep their average activity levels constant. We show that, at a central synapse in the fruit fly brain, these mechanisms include changes in presynaptic gene expression that are instructed by an abrupt loss of postsynaptic excitability. The trans-synaptically regulated genes have roles in synaptic vesicle release and synapse remodeling; protein synthesis, folding, and degradation; and energy metabolism. Our study establishes a role for transcriptional changes in homeostatic synaptic plasticity, points to mechanistic commonalities between peripheral and central synapses, and potentially opens new opportunities for the development of connectivity-based gene expression systems.

Neurogenesis occurs in adults of most organisms, both vertebrates and invertebrates. In semiterrestrial crabs of the infraorder Brachyura, the deutocerebrum, where neurogenesis occurs, processes the olfactory sensory information from the antennae. The deutocerebrum is composed of a pair of olfactory lobes associated with cell clusters 9 and 10 (Cl 9 and Cl 10), containing proliferating cells. Because the location of the neurogenic niche in brachyuran semiterrestrial crabs has not been defined, here we describe a neurogenic niche in the central olfactory system of the crab Ucides cordatus and report two types of glial cells in the deutocerebrum, based on different markers. Serotonin (5-hydroxytryptamine) labeling was used to reveal neuroanatomical aspects of the central olfactory system and the neurogenic niche. The results showed a zone of proliferating neural cells within Cl 10, which also contains III beta-tubulin (Tuj1)+ immature neurons, associated with a structure that has characteristics of the neurogenic niche. For the first time, using two glial markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS), we identified two types of astrocyte-like cells in different regions of the deutocerebrum. This study adds to the understanding of neurogenesis in a brachyuran semiterrestrial crustacean and encourages comparative studies between crustaceans and vertebrates, including mammals, based on shared aspects of both mechanisms of neurogenesis and regenerative potentials.

Convergent lines of evidence indicate a striking correlation between olfactory deficits and depressive symptoms. However, the effectiveness of intranasal treatment of antidepressant or other neurotrophic agents remains poorly understanding. Here in this study, we created depression mouse model and explored the antidepressant effects of GLP-1 analog lixisenatide (LXT) with intranasal treatment. Consecutive intranasal treatment of LXT remarkably reduced the depressive and anxiety behaviors. Meanwhile, it also improved the olfactory memory and olfactory sensitivity. Immunofluorescent analysis demonstrated the LXT improved the adult neurogenesis in olfactory system and hippocampus. Inhibition of adult neurogenesis with TMZ caused the compromised effects of LXT in improving emotional and olfactory functions, suggesting the vital role of adult neurogenesis in LXT induced depression therapeutic effects. Treatment of LXT resulted in the increased phosphorylation of CREB protein in hippocampal tissue, indicating CREB plays important roles in antidepressant effects of LXT intranasal treatment. Inhibiting CREB with chemical approach decreased effects of LXT in reserving depression induced emotional and olfactory functions. In conclusion, our study suggests intranasal treatment of LXT could be a potential antidepressant to improve the olfactory functions as well as the emotional behaviors.

In the rodent brain, the central processing of ecologically relevant chemical stimuli involves many different areas located at various levels within the neuraxis: the main and accessory olfactory bulbs, some nuclei in the amygdala, the hypothalamus, and brainstem. These areas allow the integration of the chemosensory stimuli with other sensory information and the selection of the appropriate neurohormonal and behavioral response. This review is a brief introduction to the processing of intraspecific chemosensory stimuli beyond the secondary projection, focusing on the activity of the relevant amygdala and hypothalamic nuclei, namely the medial amygdala and ventromedial hypothalamus. These areas are involved in the appropriate interpretation of chemosensory information and drive the selection of the proper response, which may be behavioral or hormonal and may affect the neural activity of other areas in the telencephalon and brainstem.Recent data support the notion that the processing of intraspecific chemical signals is not unique to one chemosensory system and some molecules may activate both the main and the accessory olfactory system. Moreover, both these systems have mixed projections and cooperate for the correct identification of the stimuli and selection of relevant responses.

The sense of smell is an essential modality for many species, in particular nocturnal and crepuscular mammals, to gather information about their environment. Olfactory cues provide information over a large range of distances, allowing behaviours ranging from simple detection and recognition of objects, to tracking trails and navigating using odour plumes from afar. In this review, we discuss the features of the natural olfactory environment and provide a brief overview of how odour information can be sampled and might be represented and processed by the mammalian olfactory system. Finally, we discuss recent behavioural approaches that address how mammals extract spatial information from the environment in three different contexts: odour trail tracking, odour plume tracking and, more general, olfactory-guided navigation. Recent technological developments have seen the spatiotemporal aspect of mammalian olfaction gain significant attention, and we discuss both the promising aspects of rapidly developing paradigms and stimulus control technologies as well as their limitations. We conclude that, while still in its beginnings, research on the odour environment offers an entry point into understanding the mechanisms how mammals extract information about space.

Background Olfactory systems take on important tasks to distinguish salient information from a complex olfactory environment, such as locating hosts, mating, aggression, selecting oviposition sites, and avoiding predators. The olfactory system of an adult insect consists of two pairs of main olfactory appendages on the head, the antennae, and the palps, which are covered with sensilla. Benzothiazole and 1-octen-3-ol could elicit oviposition behavior in gravid B. dorsalis are regarded as oviposition stimulants. However, the mechanism for how B. dorsalis percepts benzothiazole and 1-octen-3-ol still remains unknown. Results We conducted a comparative analysis of the antennal transcriptomes in different genders of B. dorsalis using Illumina RNA sequencing (RNA-seq). We identified a total of 1571 differentially expressed genes (DEGs) among the two sexes, including 450 female-biased genes and 1121 male-biased genes. Among these DEGs, we screened out 24 olfaction-related genes and validated them by qRT-PCR. The expression patterns of these genes in different body parts were further determined. In addition, we detected the expression profiles of the screened female-biased chemosensory genes in virgin and mated female flies. Furthermore, the oviposition stimulants-induced expression profilings were used to identify chemosensory genes potentially responsible for benzothiazole and 1-octen-3-ol perception in this fly. Conclusions The results from this study provided fundamental data of chemosensory DEGs in the B. dorsalis antenna. The odorant exposure assays we employed lay a solid foundation for the further research regarding the molecular mechanism of benzothiazole and 1-octen-3-ol mediated oviposition behavior in B. dorsalis.

The ability of the olfactory system to detect and discriminate a broad spectrum of odor molecules with extraordinary sensitivity relies on a wide range of odorant receptors and on the distinct architecture of neuronal circuits in olfactory brain areas. More than 1000 odorant receptors, distributed almost randomly in the olfactory epithelium, are plotted out in two mirror-symmetric maps of glomeruli in the olfactory bulb, the first relay station of the olfactory system. How does such a precise spatial arrangement of glomeruli emerge from a random distribution of receptor neurons? Remarkably, the identity of odorant receptors defines not only the molecular receptive range of sensory neurons but also their glomerular target. Despite their key role, odorant receptors are not the only determinant, since the specificity of neuronal connections emerges from a complex interplay between several molecular cues and electrical activity. This review provides an overview of the mechanisms underlying olfactory circuit formation. In particular, recent findings on the role of odorant receptors in regulating axon targeting and of spontaneous activity in the development and maintenance of synaptic connections are discussed.

With less than a million neurons, the western honeybee Apis mellifera is capable of complex olfactory behaviors and provides an ideal model for investigating the neurophysiology of the olfactory circuit and the basis of olfactory perception and learning. Here, we review the most fundamental aspects of honeybee’s olfaction: first, we discuss which odorants dominate its environment, and how bees use them to communicate and regulate colony homeostasis; then, we describe the neuroanatomy and the neurophysiology of the olfactory circuit; finally, we explore the cellular and molecular mechanisms leading to olfactory memory formation. The vastity of histological, neurophysiological, and behavioral data collected during the last century, together with new technological advancements, including genetic tools, confirm the honeybee as an attractive research model for understanding olfactory coding and learning.

Extant anuran amphibians originate from an evolutionary intersection eventually leading to fully terrestrial tetrapods. In many ways, they have to deal with exposure to both terrestrial and aquatic environments: (i) phylogenetically, as derivatives of the first tetrapod group that conquered the terrestrial environment in evolution; (ii) ontogenetically, with a development that includes aquatic and terrestrial stages connected via metamorphic remodeling; and (iii) individually, with common changes in habitat during the life cycle. Our knowledge about the structural organization and function of the amphibian olfactory system and its relevance still lags behind findings on mammals. It is a formidable challenge to reveal underlying general principles of circuity-related, cellular, and molecular properties that are beneficial for an optimized sense of smell in water and air. Recent findings in structural organization coupled with behavioral observations could help to understand the importance of the sense of smell in this evolutionarily important animal group. We describe the structure of the peripheral olfactory organ, the olfactory bulb, and higher olfactory centers on a tissue, cellular, and molecular levels. Differences and similarities between the olfactory systems of anurans and other vertebrates are reviewed. Special emphasis lies on adaptations that are connected to the distinct demands of olfaction in water and air environment. These particular adaptations are discussed in light of evolutionary trends, ontogenetic development, and ecological demands.

Olfactory marker protein (OMP) was first described as a protein expressed in olfactory receptor neurons (ORNs) in the nasal cavity. In particular, OMP, a small cytoplasmic protein, marks mature ORNs and is also expressed in the neurons of other nasal chemosensory systems: the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. While its expression pattern was more easily established, OMP’s function remained relatively vague. To date, most of the work to understand OMP’s role has been done using mice lacking OMP. This mostly phenomenological work has shown that OMP is involved in sharpening the odorant response profile and in quickening odorant response kinetics of ORNs and that it contributes to targeting of ORN axons to the olfactory bulb to refine the glomerular response map. Increasing evidence shows that OMP acts at the early stages of olfactory transduction by modulating the kinetics of cAMP, the second messenger of olfactory transduction. However, how this occurs at a mechanistic level is not understood, and it might also not be the only mechanism underlying all the changes observed in mice lacking OMP. Recently, OMP has been detected outside the nose, including the brain and other organs. Although no obvious logic has become apparent regarding the underlying commonality between nasal and extranasal expression of OMP, a broader approach to diverse cellular systems might help unravel OMP’s functions and mechanisms of action inside and outside the nose.

There are 3559 species of mosquitoes in the world (Harbach 2018) but, so far, only a handful of them have been a focus of olfactory neuroscience and neurobiology research. Here we discuss mosquito olfactory anatomy and function and connect these to mosquito ecology. We highlight the least well-known and thus most interesting aspects of mosquito olfactory systems and discuss promising future directions. We hope this review will encourage the insect neuroscience community to work more broadly across mosquito species instead of focusing narrowly on the main disease vectors.

Sensing olfactory signals in the environment represents a crucial and significant task of sensory systems in almost all organisms to facilitate survival and reproduction. Notably, the olfactory system of diverse animal phyla shares astonishingly many fundamental principles with regard to anatomical and functional properties. Binding of odor ligands by chemosensory receptors present in the olfactory peripheral organs leads to a neuronal activity that is conveyed to first and higher-order brain centers leading to a subsequent odor-guided behavioral decision. One of the key centers for integrating and processing innate olfactory behavior is the lateral horn (LH) of the protocerebrum in insects. In recent years the LH of Drosophila has garnered increasing attention and many studies have been dedicated to elucidate its circuitry. In this review we will summarize the recent advances in mapping and characterizing LH-specific cell types, their functional properties with respect to odor tuning, their neurotransmitter profiles, their connectivity to pre-synaptic and post-synaptic partner neurons as well as their impact for olfactory behavior as known so far.

Odor perception begins with the detection of odorant molecules by the main olfactory epithelium located in the nasal cavity. Odorant molecules bind to and activate a large family of G-protein-coupled odorant receptors and trigger a cAMP-mediated transduction cascade that converts the chemical stimulus into an electrical signal transmitted to the brain. Morever, odorant receptors and cAMP signaling plays a relevant role in olfactory sensory neuron development and axonal targeting to the olfactory bulb. This review will first explore the physiological response of olfactory sensory neurons to odorants and then analyze the different components of cAMP signaling and their different roles in odorant detection and olfactory sensory neuron development.

Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity.

application/pdf, Artiodactyl livestock animals have a vomeronasal system that detects pheromones. Vomeronasal receptors comprise type 1 (V1R) coupled with G protein α-i2 (Gαi2) and type 2 (V2R) coupled with G protein α-o (Gαo). Laboratory rodents have two segregated V1R and V2R pathways that reach separately to the accessory olfactory bulb (AOB). In contrast, the AOBs of goats and sheep are entirely positive for Gαi2, indicating that they have only the V1R pathway. However, we detected a few V2R genes in the genome of cattle, goats, sheep and pigs by genome assembly. Thus, we immunohistochemically analyzed the AOBs of cattle and pigs to confirm which type of the vomeronasal system is present in artiodactyl livestock species. The glomerular layer of the AOB in cattle and pigs was entirely positive for anti-Gαi2 and weakly positive for anti-Gαo, as in the V1R uniform type of vomeronasal system in other mammal species. These findings indicated that artiodactyl livestock species have a uniform type of vomeronasal system composing the V1R pathway. Therefore, caution is advised when extrapolating knowledge of laboratory rodents with two vomeronasal pathways to livestock animals that have one. © 2022 Elsevier Ltd

This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism.The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry.Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P0.05).The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium.

The sense of smell enables insects to recognize olfactory signals crucial for survival and reproduction. In insects, odorant detection highly depends on the interplay of distinct proteins expressed by specialized olfactory sensory neurons (OSNs) and associated support cells which are housed together in chemosensory units, named sensilla, mainly located on the antenna. Besides odorant-binding proteins (OBPs) and olfactory receptors, so-called sensory neuron membrane proteins (SNMPs) are indicated to play a critical role in the detection of certain odorants. SNMPs are insect-specific membrane proteins initially identified in pheromone-sensitive OSNs of Lepidoptera and are indispensable for a proper detection of pheromones. In the last decades, genome and transcriptome analyses have revealed a wide distribution of SNMP-encoding genes in holometabolous and hemimetabolous insects, with a given species expressing multiple subtypes in distinct cells of the olfactory system. Besides SNMPs having a neuronal expression in subpopulations of OSNs, certain SNMP types were found expressed in OSN-associated support cells suggesting different decisive roles of SNMPs in the peripheral olfactory system. In this review, we will report the state of knowledge of neuronal and non-neuronal members of the SNMP family and discuss their possible functions in insect olfaction. Supplementary Information The online version contains supplementary material available at 10.1007/s00441-020-03336-0.

Trace Amine-Associated Receptors (TAARs) are a family of G protein-coupled receptors that function as odorant receptors in the main olfactory system of vertebrates. TAARs are monoallelically expressed in primary sensory neurons where they couple to the same transduction cascade as canonical olfactory receptors and are mapped onto glomeruli within a specific region of the olfactory bulb. TAARs have a high affinity for volatile amines, a class of chemicals that are generated during the decomposition of proteins and are ubiquitous physiological metabolites that are found in body fluids. Thus, amines are proposed to play an important role in intra- and interspecific communication such as signaling the sex of the conspecific, the quality of the food source, or even the proximity of a predator. TAARs have a crucial role in the perception of these behaviorally relevant compounds as the genetic deletion of all or even individual olfactory TAARs can alter the behavioral response and reduce the sensitivity to amines. The small size of this receptor family combined with the ethological relevance of their ligands, makes the TAARs an attractive model system for probing olfactory perception. This review will summarize the current knowledge on the olfactory TAARs and discuss whether they represent a unique subsystem within the main olfactory system.

The domestic dog is assumed by nearly everyone to be the consummate smeller. Within the species Canis familiaris individual breeds, such as the bloodhound or beagle, are known as olfactory stars. These are "scent breeds," a grouping variably defined as a genetic clade or breed class commonly used for scent detection tasks. Previous work suggests that the dog has a more robust olfactory anatomy than many mammal species. Now we undertake a closer investigation of the dog's olfactory system, both in relationship to its closest wild relatives, the wolf and coyote, and across individual breeds. First, we seek to resolve whether the dog has lost olfactory capacity through its domestication from the wolf lineage. Second, we test the inertial lore that among dogs, "scent breeds," have a superior olfactory facility. As a measure of relative olfactory capacity, we look to the cribriform plate (CP), a bony cup in the posterior nasal cavity perforated by passageways for all olfactory nerve bundles streaming from the periphery to the brain. Using high-resolution computed tomography (CT) scans and digital quantification, we compare relative CP size in 46 dog breeds, the coyote and gray wolf. Results show the dog has a reduced CP surface area relative to the wolf and coyote. Moreover, we found no significant differences between CP size of "scent" and "non-scent" breeds. Our study suggests that the dog lost olfactory capacity as a result of domestication and this loss was not recovered in particular breed groupings through directed artificial selection for increased olfactory facility.

Animal behavior is encoded in neuronal circuits in the brain. To elucidate the function of these circuits, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace (Botulinum-Activated Tracer), a genetically encoded, retrograde, transsynaptic labeling system. BAcTrace is based on Clostridium botulinum neurotoxin A, Botox, which we engineered to travel retrogradely between neurons to activate an otherwise silent transcription factor. We validated BAcTrace at three neuronal connections in the Drosophila olfactory system. We show that BAcTrace-mediated labeling allows electrophysiological recording of connected neurons. Finally, in a challenging circuit with highly divergent connections, BAcTrace correctly identified 12 of 16 connections that were previously observed by electron microscopy. BAcTrace is a predominantly retrograde tracing tool for connectomic analyses in Drosophila.

Many insects possess the ability to detect fine fluctuations in the environmental CO2 concentration. In herbivorous species, plant-emitted CO2, in combination with other sensory cues, affect many behaviors including foraging and oviposition. In contrast to the comprehensive knowledge obtained on the insect olfactory pathway in recent years, we still know little about the central CO2 system. By utilizing intracellular labeling and mass staining, we report the neuroanatomy of projection neurons connected with the CO2 sensitive antennal-lobe glomerulus, the labial pit organ glomerulus (LPOG), in the noctuid moth, Helicoverpa armigera. We identified 15 individual LPOG projection neurons passing along different tracts. Most of these uniglomerular neurons terminated in the lateral horn, a previously well-described target area of plant-odor projection neurons originating from the numerous ordinary antennal-lobe glomeruli. The other higher-order processing area for odor information, the calyces, on the other hand, was weakly innervated by the LPOG neurons. The overlapping LPOG terminals in the lateral horn, which is considered important for innate behavior in insects, suggests the biological importance of integrating the CO2 input with plant odor information while the weak innervation of the calyces indicates the insignificance of this ubiquitous cue for learning mechanisms.

New neurons are continuously generated in the adult brain through a process called adult neurogenesis. This form of plasticity has been correlated with numerous behavioral and cognitive phenomena, but it remains unclear if and how adult-born neurons (abNs) contribute to mature neural circuits. We established a highly specific and efficient experimental system to target abNs for causal manipulations. Using this system with chemogenetics and imaging, we found that abNs effectively sharpen mitral cells (MCs) tuning and improve their power to discriminate among odors. The effects on MCs responses peaked when abNs were young and decreased as they matured. To explain the mechanism of our observations, we simulated the olfactory bulb circuit by modelling the incorporation of abNs into the circuit. We show that higher excitability and broad input connectivity, two well-characterized features of young neurons, underlie their unique ability to boost circuit computation., Shani-Narkiss et al. established an experimental system to test the functional role of adult born neurons (ABNs) on Mitral Cell (MC) coding. Silencing ABNs, unexpectedly, quenched MC odor responses. A computational model provides a mechanistic explanation to the functional role of adult-born neurons in circuit computation of the olfactory bulb.

Diltiazem is ubiquitously prescribed and has been reported in many effluents and freshwater bodies. Being a calcium channel blocker, diltiazem could disrupt the function of the sensory and central nervous systems. In the present study, using electro-olfactography (EOG), we investigated the interaction of diltiazem with the olfactory sensory neurons (OSNs) of rainbow trout by looking into the detection threshold and effects of immediate (~5 min) and acute (24 h) exposure to diltiazem at 6.6, 66, and 660 µg/L. We also studied the accumulation of the drug in fish plasma and whole body. Brief exposure to diltiazem impaired the OSN response to a chemosensory stimulus in a concentration-dependent manner at 6.6 µg/L and higher, whereas OSNs exposed for 24 h only displayed an impairment at 660 µg/L. Chemical analysis showed that the accumulation of diltiazem in fish plasma and body correlated with the EOG response because it was 10 times higher in the group that displayed a significant impairment (660 µg/L) compared to the other 2 groups (6.6, 66 µg/L). This correlation suggests that the impact of diltiazem on OSNs might partially be through the accumulated molecules in the fish bloodstream. Fish did not detect diltiazem as a sensory stimulus even at concentrations as high as 660 µg/L; thus, fish could potentially swim toward or fail to escape harmful concentrations of diltiazem. Environ Toxicol Chem 2022;41:554-550. © 2020 SETAC.

Odors activate distributed ensembles of neurons within the piriform cortex, forming cortical representations of odor thought to be essential to olfactory learning and behaviors. This odor response is driven by direct input from the olfactory bulb, but is also shaped by a dense network of associative or intracortical inputs to piriform, which may enhance or constrain the cortical odor representation. With optogenetic techniques, it is possible to functionally isolate defined inputs to piriform cortex and assess their potential to activate or inhibit piriform pyramidal neurons. The anterior olfactory nucleus (AON) receives direct input from the olfactory bulb and sends an associative projection to piriform cortex that has potential roles in the state-dependent processing of olfactory behaviors. Here, we provide a detailed functional assessment of the AON afferents to piriform in male and female C57Bl/6J mice. We confirm that the AON forms glutamatergic excitatory synapses onto piriform pyramidal neurons; and while these inputs are not as strong as piriform recurrent collaterals, they are less constrained by disynaptic inhibition. Moreover, AON-to-piriform synapses contain a substantial NMDAR-mediated current that prolongs the synaptic response at depolarized potentials. These properties of limited inhibition and slow NMDAR-mediated currents result in strong temporal summation of AON inputs within piriform pyramidal neurons, and suggest that the AON could powerfully enhance activation of piriform neurons in response to odor.SIGNIFICANCE STATEMENTOdor information is transmitted from olfactory receptors to olfactory bulb, and then to piriform cortex, where ensembles of activated neurons form neural representations of the odor. While these ensembles are driven by primary bulbar afferents, and shaped by intracortical recurrent connections, the potential for another early olfactory area, the anterior olfactory nucleus (AON), to contribute to piriform activity is not known. Here, we use optogenetic circuit-mapping methods to demonstrate that AON inputs can significantly activate piriform neurons, as they are coupled to NMDAR currents and to relatively modest disynaptic inhibition. The AON may enhance the piriform odor response, encouraging further study to determine the states or behaviors through which AON potentiates the cortical response to odor.