Odor Aversion Research Articles

Conditioned odor aversion as a tool for reducing post‐release predation during animal translocations

AbstractPredation is a key factor in prey population dynamics and could impact population recovery. One common means employed to recover prey populations is that of translocations, but most fail owing to high predation during the early stages. We tested whether conditioned odor aversion can reduce predation during animal translocations by using the predation of the European rabbit Oryctolagus cuniculus by the red fox Vulpes vulpes as a case study. Following a before‐after control‐impact design (BACI), we deployed bait stations monitored using camera‐traps in two zones to which rabbits were translocated. One week before the rabbits were released, microencapsulated levamisole was added to rabbit baits located in the treatment zones, along with vanilla essence as an odor cue. A total of 148 rabbits were distributed in artificial warrens with the odor cue and 68 of them were fitted with radio collars in order to determine their survival rates. The response to the treatment and translocation as regards subsequent rabbit abundance was evaluated using N‐mixture models, while rabbit establishment was evaluated using a warren use index (WUI). The treatment decreased the proportion of baits consumed by foxes, but this decrease was partially compensated by other predators. WUI and rabbit population growth increased significantly more after translocations in the treatment zones than in the control zones. The short‐term survival of translocated rabbits was also higher in the treatment zones than in the control zones. Our study showed that conditioned odor aversion reduced rabbit predation by foxes, and had a positive effect on rabbit population growth after translocation, since there was an increase in rabbit survival and warren establishment. This method could be used as a non‐lethal tool for the recovery of a key prey when carrying out programs concerning the reintroduction of endangered predators or for other vulnerable species requiring translocations.

Mixtures of Sweeteners and Maltodextrin Enhance Flavor and Intake of Alcohol in Adolescent Rats.

Sweet flavorants enhance palatability and intake of alcohol in adolescent humans. We asked whether sweet flavorants have similar effects in adolescent rats. The inherent flavor of ethanol in adolescent rats is thought to consist of an aversive odor, bitter/sweet taste, and burning sensation. In Experiment 1, we compared ingestive responses of adolescent rats to 10% ethanol solutions with or without added flavorants using brief-access lick tests. We used 4 flavorants, which contained mixtures of saccharin and sucrose or saccharin, sucrose, and maltodextrin. The rats approached (and initiated licking from) the flavored ethanol solutions more quickly than they did unflavored ethanol, indicating that the flavorants attenuated the aversive odor of ethanol. The rats also licked at higher rates for the flavored than unflavored ethanol solutions, indicating that the flavorants increased the naso-oral acceptability of ethanol. In Experiment 2, we offered rats chow, water, and a flavored or unflavored ethanol solution every other day for 8 days. The rats consistently consumed substantially more of the flavored ethanol solutions than unflavored ethanol across the 8 days. When we switched the rats from the flavored to unflavored ethanol for 3 days, daily intake of ethanol plummeted. We conclude that sweet and sweet/maltodextrin flavorants promote high daily intake of ethanol in adolescent rats (i.e., 6-10 g/kg) and that they do so in large part by improving the naso-oral sensory attributes of ethanol.

Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts

Animals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-DD-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/- mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.

Foraging experience modulates response to aversive odour cues in social wasps

Experience can modify how animals respond to relevant stimuli from their environment, for example, through associative learning. In particular, odour stimuli play a central role in foraging by influencing decision making. Numerous studies have shown that odours can acquire relevance for an animal by becoming associated with food after appetitive experience. Therefore, studying to what extent learning can modulate the behavioural response to olfactory stimuli is essential to improve our understanding about the role of experience in food exploitation in nature. Here, we evaluated whether foraging experience can modulate the response of Vespula germanica , a food generalist and opportunistic eusocial wasp, towards an aversive odour. Through field experiments, we evaluated the response of naïve and experienced wasps towards an aversive odour under different scenarios, to also examine how these changes affect foraging decisions. Both naïve wasps and wasps that had foraging experience in the absence of the aversive odour were not attracted to the odour alone and avoided meat sources paired with this cue. However, wasps that had foraging experience with the aversive odour showed an opposite behavioural pattern; they preferred meat sources with the aversive odour and were equally attracted to this odour and the meat source. The behavioural repertoire (i.e. approaches, landings and search behaviour) elicited by the aversive odour after experience with it indicates that change in the response was due to associative learning, leading the odour which was initially repellent, to become attractive. Interestingly, the change in the aversive odour's valence occurred after one collecting experience and three to five visits promoted long-term memory of the odour. In conclusion, our results show that spontaneous responses to odours can be modulated by experience and provide new insights about learning and memory abilities of social wasps in relation to olfactory cues. • Foraging experience can modulate the response to olfactory cues in eusocial wasps. • An initially aversive odour can become attractive after appetitive experiences. • Foragers can learn to associate odours with protein-rich sources as reward. • We found long-term memory after 24 h related to the attractiveness of the odour. • Single appetitive experiences can notably impact foraging decisions.

Cannabinoid CB2 receptors mediate the anxiolytic-like effects of monoacylglycerol lipase inhibition in a rat model of predator-induced fear

The endocannabinoid system is a key regulator of the response to psychological stress. Inhibitors of monoacylglycerol lipase (MGL), the enzyme that deactivates the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), exert anxiolytic-like effects in rodent models via 2-AG-dependent activation of CB1 cannabinoid receptors. In the present study, we examined whether the MGL inhibitor JZL184 might modulate persistent predator-induced fear in rats, a model that captures features of human post-traumatic stress disorder. Exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a volatile chemical that is innately aversive to some rodent species, produced in male rats a long-lasting anxiety-like state that was measured 7 days later in the elevated plus maze test. Systemic administration of JZL184 [4, 8 and 16 mg/kg, intraperitoneal (IP)] 4 h before testing caused dose-dependent inhibition of MGL activity and elevation of 2-AG content in brain tissue. Concomitantly, the inhibitor suppressed TMT-induced fear behaviors with a median effective dose (ED50) of 4 mg/kg. A similar behavioral response was observed with another MGL inhibitor, KML29 (4 and 16 mg/kg, IP). Surprisingly, the effect of JZL184 was prevented by co-administration of the CB2 inverse agonist AM630 (5 mg/kg, IP), but not the CB1 inverse agonist rimonabant (1 mg/kg, IP). Supporting mediation of the response by CB2 receptors, the CB2 agonist JWH133 (0.3, 1 and 3 mg/kg, IP) also produced anxiolytic-like effects in TMT-stressed rats, which were suppressed by AM630. Notably, (i) JWH133 was behaviorally ineffective in animals that had no prior experience with TMT; and (ii) CB2 mRNA levels in rat prefrontal cortex were elevated 7 days after exposure to the aversive odorant. The results suggest that JZL184 attenuates the behavioral consequences of predator stress through a mechanism that requires 2-AG-mediated activation of CB2 receptors, whose transcription may be induced by the stress itself.

Methods for independently manipulating palatability and color in small insect prey.

Understanding how the psychology of predators shapes the defenses of colorful aposematic prey has been a rich area of inquiry, with emphasis on hypothesis-driven experiments that independently manipulate color and palatability in prey to examine predator responses. Most of these studies focus on avian predators, despite calls to consider more taxonomically diverse predators. This taxonomic bias leaves gaps in our knowledge about the generalizability of current theory. Here we have adapted tools that have been successfully used with bird predators and scaled them down and tested them with smaller predators (Habronattus jumping spiders) and small insect prey (termites, milkweed bug nymphs, pinhead crickets, fruit flies). Specifically, we test (1) the application of denatonium benzoate (DB) to the surface of live termites, crickets, and fruit flies, and (2) the effectiveness of manipulating the palatability of milkweed bug nymphs through diet. We also test the effectiveness of combining these palatability manipulations with various color manipulations. Across several experiments, we confirm that our palatability manipulations are not detectable to the spiders before they attack (i.e., they do not produce aversive odors that spiders avoid), and show that unpalatable prey are indeed quickly rejected and spiders do not habituate to the taste with experience. We also investigate limitations of these techniques by assessing possible unintended effects on prey behavior and the risk of contact contamination when using DB-treated prey in experiments. While similar tools have been used to manipulate color and palatability with avian predators and relatively large insect prey, we show how these techniques can be effectively adapted for use with small invertebrate predators and prey.

Skeletal muscle thermogenesis induction by exposure to predator odor.

Non-shivering thermogenesis can promote negative energy balance and weight loss. In this study, we identified a contextual stimulus that induces rapid and robust thermogenesis in skeletal muscle. Rats exposed to the odor of a natural predator (ferret) showed elevated skeletal muscle temperatures detectable as quickly as 2 min after exposure, reaching maximum thermogenesis of >1.5°C at 10-15 min. Mice exhibited a similar thermogenic response to the same odor. Ferret odor induced a significantly larger and qualitatively different response from that of novel or aversive odors, fox odor or moderate restraint stress. Exposure to predator odor increased energy expenditure, and both the thermogenic and energetic effects persisted when physical activity levels were controlled. Predator odor-induced muscle thermogenesis is subject to associative learning as exposure to a conditioned stimulus provoked a rise in muscle temperature in the absence of the odor. The ability of predator odor to induce thermogenesis is predominantly controlled by sympathetic nervous system activation of β-adrenergic receptors, as unilateral sympathetic lumbar denervation and a peripherally acting β-adrenergic antagonist significantly inhibited predator odor-induced muscle thermogenesis. The potential survival value of predator odor-induced changes in muscle physiology is reflected in an enhanced resistance to running fatigue. Lastly, predator odor-induced muscle thermogenesis imparts a meaningful impact on energy expenditure as daily predator odor exposure significantly enhanced weight loss with mild calorie restriction. This evidence signifies contextually provoked, centrally mediated muscle thermogenesis that meaningfully impacts energy balance.

A Masked Aversive Odor Cannot Be Discriminated From the Masking Odor but Can Be Identified Through Odor Quality Ratings and Neural Activation Patterns.

Odor masking is a very prominent problem in our daily routines, mainly concerning unpleasant sweat or toilet odors. In the current study we explored the effectiveness of odor masking both on a behavioral and neuronal level. By definition, participants cannot differentiate a fully masked unpleasant odor from the pleasant pure odor used as a masking agent on a behavioral level. We hypothesized, however, that one can still discriminate between a fully masked odor mixture and the pure masking odor on a neuronal level and that, using a reinforcing feedback paradigm, participants could be trained to perceive this difference. A pleasant, lemon-like odor (citral) and a mixture of citral and minor amounts of an unpleasant, goat-like odor (caproic acid) were presented to participants repeatedly using a computer-controlled olfactometer and participants had to decide whether two presented stimuli were the same or different. Accuracy of this task was incentivized with a possible monetary reward. Functional imaging was used throughout the task to investigate central processing of the two stimuli. The participants rated both stimuli as isopleasant and isointense, indicating that the unpleasant odor was fully masked by the pleasant odor. The isolated caproic acid component of the mixture was rated less pleasant than the pleasant odor in a prior experimental session. Although the masked and pure stimuli were not discriminated in the forced-choice task, quality ratings on a dimensional scale differed. Further, we observed an increased activation of the insula and ventral striatum/putamen for the pure in contrast to the fully masked odor, hence revealing a difference in neuronal processing. Our hypothesis that perceptual discrimination and neuronal processing can be enhanced using a reinforcing feedback paradigm is not supported by our data.

Bcl11b controls odorant receptor class choice in mice

Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) gene from the class I or class II repertoire in mice. The mechanisms that regulate OR class choice in OSNs remain unknown. Here, we show that the transcription factor Bcl11b determines the OR class to be expressed in OSNs. Both loss- and gain-of-function analyses demonstrate that class I is a default fate of OSNs and that Bcl11b dictates a class II OR choice by suppressing the effect of the J-element, a class I-OR enhancer. We further demonstrate that OSN-specific genetic manipulations of Bcl11b bias the OR class choice, generating mice with “class I-dominant” and “class II-dominant” noses, which display contrasting innate olfactory behaviors to two distinct aversive odorants. Overall, these findings reveal a unique transcriptional mechanism mediating a binary switch for OR class choice that is crucial to both the anatomical and functional organization of the olfactory system.

CB1 Receptors in the Anterior Piriform Cortex Control Odor Preference Memory

The retrieval of odor-related memories shapes animal behavior. The anterior piriform cortex (aPC) is the largest part of the olfactory cortex, and it plays important roles in olfactory processing and memory. However, it is still unclear whether specific cellular mechanisms in the aPC control olfactory memory, depending on the appetitive or aversive nature of the stimuli involved. Cannabinoid-type 1 (CB1) receptors are present in the aPC (aPC-CB1), but their potential impact on olfactory memory was never explored. Here, we used a combination of behavioral, genetic, anatomical, and electrophysiological approaches to characterize the functions of aPC-CB1 receptors in the regulation of appetitive and aversive olfactory memory. Pharmacological blockade or genetic deletion of aPC-CB1 receptors specifically impaired the retrieval of conditioned odor preference (COP). Interestingly, expression of conditioned odor aversion (COA) was unaffected by local CB1 receptor blockade, indicating that the role of aPC endocannabinoidsignaling is selective for retrieval of appetitive memory. Anatomical investigations revealed thatCB1 receptors are highly expressed on aPC GABAergic interneurons, and exvivo electrophysiological recordings showed that their pharmacological activation reduces miniature inhibitory post-synaptic currents (mIPSCs) onto aPC semilunar (SL), but not pyramidal principal neurons. COP retrieval, but not COA, was associated with a specific CB1-receptor-dependent decrease of mIPSCs in SL cells. Altogether, these data indicate that aPC-CB1 receptor-dependent mechanisms physiologically control the retrieval of olfactory memory, depending on odor valence and engaging modulation of local inhibitory transmission.

NMDA receptor and nitric oxide synthase activity in the central amygdala is involved in the acquisition and consolidation of conditioned odor aversion

Rats readily learn to avoid a tasteless odorized solution if they experience visceral malaise after consuming it. This phenomenon is referred to as conditioned odor aversion (COA). Several studies have shown that COA depends on the functional integrity of the amygdala, with most studies focusing on the basolateral nucleus. On the other hand, the role of the central amygdala (CeA) which is known to be involved in the consolidation of conditioned taste aversion (CTA) remains to be established. To address this issue, we evaluated the effect of inhibiting NMDA receptor activity in this structure on COA memory formation. Intra-CeA infusions of non-competitive NMDA receptor inhibitor MK-801 prevented memory formation both when administered before and up to 15 min after COA conditioning, while no effect of this drug was observed when given before long-term memory test. We next evaluated the role of one of the main downstream effectors of brain NMDA receptor signaling, nitric oxide synthase (NOS), known to play a key role in a wide variety learning tasks including some types of olfactory conditioning. Similar results were obtained with inhibition of either NOS or neuron-specific NOS; which proved to be required both during and after COA training, though for a shorter time span than NMDA receptors. Also, neither isoform showed to be required to memory retrieval. These results suggest that the US signaling during acquisition and the initial consolidation step of COA depends on glutamate-NO system activation in the CeA.

Olfactory and Neuromodulatory Signals Reverse Visual Object Avoidance to Approach in Drosophila

Behavioral reactions of animals to environmental sensory stimuli are sometimes reflexive and stereotyped but can also vary depending on contextual conditions. Engaging in active foraging or flight provokes a reversal in the valence of carbon dioxide responses from aversion to approach in Drosophila [1, 2], whereas mosquitoes encountering this same chemical cue show enhanced approach toward a small visual object [3]. Sensory plasticity in insects has been broadly attributed to the action of biogenic amines, which modulate behaviors such as olfactory learning, aggression, feeding, and egg laying [4-14]. Octopamine acts rapidly upon the onset of flight to modulate the response gain of directionally selective motion-detecting neurons in Drosophila [15]. How the action of biogenic amines might couple sensory modalities to each other or to locomotive states remains poorly understood. Here, we use a visual flight simulator [16] equipped for odor delivery [17] to confirm that flies avoid a small contrasting visual object in odorless air [18] but that the same animals reverse their preference to approach in the presence of attractive food odor. An aversive odor does not reverse object aversion. Optogenetic activation of either octopaminergic neurons or directionally selective motion-detecting neurons that express octopamine receptors elicits visual valence reversal in the absence of odor. Our results suggest a parsimonious model in which odor-activated octopamine release excites the motion detection pathway to increase the saliency of either a small object or a bar, eliciting tracking responses by both visual features.

Conditioned food aversion mediated by odour cue and microencapsulated levamisole to avoid predation by canids

Worldwide, predators and humans are in conflict for resources such as game species or livestock, especially in the case of wild canids. One non-lethal method to reduce predation is conditioned food aversion (CFA), in which animals learn to avoid a food due to the illness after ingestion, caused by the addition of an undetected chemical compound. CFA can be enhanced by adding an artificial odour cue, in a process known as taste-potentiated odour aversion (TPOA). We tested CFA and TPOA with three experimental groups of penned dogs. Food was offered with a combination of microencapsulated levamisole + vanilla odour (ODO), microencapsulated levamisole (LEV), or plain food as a control. The aims were (a) to test whether dogs detected the microencapsulated levamisole, (b) to analyse the strength and extinction time of CFA induced by microencapsulated levamisole, and (c) to analyse the strength and extinction time of TPOA. Two-choice tests were carried out during 11 post-conditioning months, and two reinforcements with microencapsulated levamisole were performed during the first post-conditioning month. In the first post-conditioning test, ODO and LEV groups ate significantly less untreated food than control group. After reinforcement, the dogs in LEV group resumed eating the food. Three of four dogs in ODO group showed long-lasting CFA until the 11th month. These results show that TPOA could be used to induce odour aversion on canids and that the odour cue overshadows the slight bitter taste of microencapsulated levamisole. These results show TPOA as a promising tool to reduce predation by wild canids.

Corticosteroid-Binding Globulin Deficiency Specifically Impairs Contextual and Recognition Memory Consolidation in Male Mice

Background/Aims: Glucocorticoids are essential in modulating memory processes of emotionally arousing experiences and we have shown that corticosteroid-binding globulin (CBG) influences glucocorticoid delivery to the brain. Here, we investigated the role of CBG in contextual and recognition long-term memory according to stress intensity. Method: We used adult male mice totally deficient in CBG (Cbg KO) or brain-specific Cbg KO (Cbg^Camk KO) to examine their performance in contextual fear conditioning (CFC) and au­ditory fear conditioning, both at short (1 h) and long-term (24 h). Long-term memory in Cbg KO was further analyzed in conditioned odor aversion and in novel object recognition task (NORT) with different paradigms, that is, with and without prior habituation to the context, with a mild or strong stressor applied during consolidation. In the NORT experiments, total and free glucocorticoid levels were measured during consolidation. Results: Impaired memory was observed in the Cbg KO but not in the Cbg^Camk KO in the CFC and the NORT without habituation when tested 24 h later. However, Cbg KO displayed normal behavior in the NORT with previous habituation and in the NORT with a mild stressor. In condition of the NORT with a strong stressor, Cbg KO retained good 24 h memory performance while controls were impaired. Total and free glucocorticoids levels were always higher in controls than in Cbg KO except in NORT with mild stressor where free glucocorticoids were equivalent to controls. Conclusions: These data indicate that circulating but not brain CBG influences contextual and recognition long-term memory in relation with glucocorticoid levels.

Extrafield Activity Shifts the Place Field Center of Mass to Encode Aversive Experience.

Hippocampal place cells are known to have a key role in encoding spatial information. Aversive stimuli, such as predator odor, evoke place field remapping and a change in preferred firing locations. However, it remains unclear how place cells use positive or negative experiences to remap. We investigated whether CA1 place cells, recorded from behaving rats, remap randomly or whether their reconfiguration depends on the perceived location of the aversive stimulus. Exposure to trimethylthiazoline (TMT; an innately aversive odor), increased the amplitude of hippocampal β oscillations in the two arms of the maze in which TMT exposure occurred. We found that a population of place cells with fields located outside the TMT arms increased their activity (extrafield spiking) in the TMT arms during the aversive episodes. Moreover, in the subsequent post-TMT recording, these cells exhibited a significant shift in their center of mass (COM) towards the TMT arms. The induction of extrafield plasticity was mediated by the basolateral amygdala complex (BLA). Photostimulation of the BLA triggered aversive behavior, synchronized hippocampal local field oscillations, and increased the extrafield spiking of the hippocampal place cells for the first 100 ms after light delivery. Optogenetic BLA activation triggered an increase in extrafield spiking activity that was correlated with the degree of place field plasticity. Furthermore, BLA-mediated increase of the extrafield activity predicts the degree of subsequent field plasticity. Our findings demonstrate that that the remapping of hippocampal place cells during aversive episodes is not random but it depends on the location of the aversive stimulus.

The influence of olfactory disgust on (Genital) sexual arousal in men

BackgroundThe generation or persistence of sexual arousal may be compromised when inhibitory processes such as negative emotions, outweigh sexual excitation. Disgust particularly, has been proposed as one of the emotions that may counteract sexual arousal. In support of this view, previous research has shown that disgust priming can reduce subsequent sexual arousal. As a crucial next step, this experimental study tested whether disgust (by means of odor) can also diminish sexual arousal in individuals who are already in a state of heightened sexual excitation.MethodologyIn this study, participants were all men (N = 78). To elicit sexual arousal, participants watched a pornographic video. Following 4.30 minutes from the start of the video clip, they were exposed to either a highly aversive/disgusting odor (n = 42), or an odorless diluent/solvent (n = 36), that was delivered via an olfactometer, while the pornographic video continued. In both conditions the presentation of the odor lasted 1 second and was repeated 11 times with intervals of 26 seconds. Sexual arousal was indexed by both self-reports and penile circumference.Principal findingsThe disgusting odor (released when the participants were already sexually aroused) resulted in a significant decrease of both subjective and genital sexual arousal compared to the control (odorless) condition.SignificanceThe finding that the inhibitory effect of disgust was not only expressed in self-report but also expressed on the penile response further strengthens the idea that disgust might hamper behavioral actions motivated by sexual arousal (e.g., poor judgment, coercive sexual behavior). Thus, the current findings indicate that exposure to an aversive odor is sufficiently potent to reduce already present (subjective and) genital sexual arousal. This finding may also have practical relevance for disgust to be used as a tool for self-defence (e.g., Invi Bracelet).

Accessing Olfactory Habituation in Drosophila melanogaster with a T-maze Paradigm.

Habituation is the process whereby perceptual changes alter the value of environmental stimuli, enabling salience filtering. This behavioral response decrement is a form of non-associative learning, where the subject learns about the stimulus and does not involve sensory adaptation, sensory or motor fatigue. The range of behavioral responses in D. melanogaster led to the development of a number of habituation paradigms addressing various sensory modalities. Habituation of osmotactic responses has previously been measured with the Y-maze test and required 30 min of odor exposure. Here, we describe an olfactory habituation assay utilizing the widely used in associative learning paradigms T-maze. Continuous or repetitive odor exposure for 4 min is adequate to attenuate osmotactic responses both to attractive and aversive odors. Importantly, the decreased response conforms to habitation parameters, presenting dishabituation and spontaneous recovery. This assay allows the study of habituation after brief odor exposure, but also discriminates between the two distinct phases of the response, an initial habituation latency period followed by habituation. In addition, the characterization of the neuronal circuits implicated in each phase facilitates further study of the molecular components underlying this process.

Optogenetic Food Odor Avoidance Assay.

Appetite is tightly linked to the sensory experience of feeding, including the smell, taste, and sight of food. Sensory perception can affect the palatability of food, modulating appetite beyond homeostatic requirements. Hypothalamic neurons that govern feeding are responsive to sensory cues associated with food, including food odors. However, the circuit mechanisms by which sensory information is processed and relayed to feeding nodes to affect feeding behavior is not well understood. Recent work has identified a population of excitatory basal forebrain neurons that modulate potent appetite suppression, as well as respond to food-associated and innately aversive odorants. To investigate this circuitry, we stereotaxically targeted virus expressing Cre-dependent channelrhodopsin to the basal forebrain and implanted fiber optic cannulas over the injection site. Mice were allowed to recover and underwent training to form a passive association of chow with a unique monomolecular odorant. After training, mice were fasted overnight, and were then presented with both the food-associated odor as well as a similar, novel odor in zones of an arena with and without photostimulation. To evaluate whether stimulation of this circuitry influenced sensory modulation of feeding behavior, video recording and behavioral tracking analysis were used to compare time spent investigating either odor. Thus, this protocol provides a useful paradigm to assay the contribution of different circuits in appetitive and aversive behaviors.

Implicit Affective Rivalry: A Behavioral and fMRI Study Combining Olfactory and Auditory Stimulation.

Aversive odors are highly salient stimuli that serve a protective function. Thus, emotional reactions elicited by negative odors may be hardly influenceable. We aim to elucidate if negative mood induced by negative odors can be modulated automatically by positively valenced stimuli. We included 32 healthy participants (16 men) in an fMRI design combining aversive and neutral olfactory stimuli with positive and neutral auditory stimuli to test the influence of aversive olfactory stimuli on subjective emotional state and brain activation when combined with positive and neutral auditory stimuli. The behavioral results show an interaction of negative olfactory stimuli on ratings of disgust, perceived valence of music, and subjective affective state, while positive auditory stimulation did not show this interaction. On a neuronal level, we observed main effects for auditory and olfactory stimulation, which are largely congruent with previous literature. However, the pairing of both stimuli was associated with attenuated brain activity in a set of brain areas (supplementary motor area, temporal pole, superior frontal gyrus) which overlaps with multisensory processing areas and pave the way for automatic emotion regulation. Our behavioral results and the integrated neural patterns provide evidence of predominance of olfaction in processing of affective rivalry from multiple sensory modalities.

Microdialysis Unveils the Role of the α2-Adrenergic System in the Basolateral Amygdala during Acquisition of Conditioned Odor Aversion in the Rat.

Previous work has shown that β-adrenergic and GABAergic systems in the basolateral amygdala (BLA) are involved in the acquisition of conditioned odor aversion (COA) learning. The involvement of α2-adrenoreceptors, however, is poorly documented. In a first experiment, male Long-Evans rats received infusions of 0.1 μg of the selective α2-antagonist dexefaroxan (Dex) in the BLA before being exposed to COA learning. In a second experiment, levels of norepinephrine (NE) were analyzed following Dex retrodialysis into the BLA. While microdialysis data showed a significant enhancement of NE release in the BLA with Dex, behavioral results showed that pre-CS infusion of Dex impaired, rather than facilitated, the acquisition of COA. Our results show that the NE system in the BLA is involved in the acquisition of COA, including a strong α2-receptor modulation until now unsuspected. Supported by the recent literature, the present data suggest moreover that the processes underlying this learning are probably mediated by the balanced effects of NE excitatory/inhibitory signaling in the BLA, in which interneurons are highly involved.