Odor enrichment increases interneurons responsiveness in spatially defined regions of the olfactory bulb correlated with perception

Odor enrichment enhances rats’ ability to discriminate between chemically similar odorants. We show here that this modulation of olfactory perception is accompanied by increases in the density of local inhibitory interneuron expressing Zif268 in response to olfactory stimuli. These changes depend on the overlap of the olfactory bulb activation patterns induced by the enrichment odorants with those induced by the testing odorants, in a manner similar to changes in perception. Moreover, we show that enrichment leads to an alteration of the pattern of Zif268 expression, dependent on the odors used for the enrichment indicating a restructuring of odor representation in the olfactory bulb.     

The role of attention in the localization of odors to the mouth

Odors can be perceived as arising from the environment or as part of a flavor located in the mouth. One factor that may dictate where an odor is perceived to be is concurrent gustatory stimulation in the mouth. A taste may impair the ability to attend to an odor, especially if they are perceptually similar. Alternatively, salient mouth-based features of a flavor might command attention at the expense of smell. Experiment 1 and 2, using different stimulus sets, explored the impact of perceptually similar and dissimilar pairings of tastes in the mouth and odors at the nose. In each case, these were followed by judgments of the odor's location (mouth vs. nose). Perceptual similarity had no impact on localization judgments. Experiment 3 then manipulated the salience of the olfactory and gustatory cues and showed that each could independently shift the perceived location of an odorant-salient olfactory cues toward the nose and gustatory cues toward the mouth. These findings suggest that the salient features of a flavor may command attention at the expense of olfaction and, thereby, contribute to oral localization, with implications for flavor binding.     

Mitral cell beta1 and 5-HT2A receptor colocalization and cAMP coregulation: a new model of norepinephrine-induced learning in the olfactory bulb

In the present study we assess a new model for classical conditioning of odor preference learning in rat pups. In preference learning beta(1)-adrenoceptors activated by the locus coeruleus mediate the unconditioned stimulus, whereas olfactory nerve input mediates the conditioned stimulus, odor. Serotonin (5-HT) depletion prevents odor learning, with 5-HT(2A/2C) agonists correcting the deficit. Our new model proposes that the interaction of noradrenergic and serotonergic input with odor occurs in the mitral cells of the olfactory bulb through activation of cyclic adenosine monophosphate (cAMP). Here, using selective antibodies and immunofluorescence examined with confocal microscopy, we demonstrate that beta(1)-adrenoceptors and 5-HT(2A) receptors colocalize primarily on mitral cells. Using a cAMP assay and cAMP immunocytochemistry, we find that beta-adrenoceptor activation by isoproterenol, at learning-effective and higher doses, significantly increases bulbar cAMP, as does stroking. As predicted by our model, the cAMP increases are localized to mitral cells. 5-HT depletion of the olfactory bulb does not affect basal levels of cAMP but prevents isoproterenol-induced cAMP elevation. These results support the model. We suggest the mitral-cell cAMP cascade converges with a Ca(2+) pathway activated by odor to recruit CREB phosphorylation and memory-associated changes in the olfactory bulb. The dose-related increase in cAMP with isoproterenol implies a critical cAMP window because the highest dose of isoproterenol does not produce learning.     

Noradrenergic control of odor recognition in a nonassociative olfactory learning task in the mouse

The present study examined the influence of pharmacological modulations of the locus coeruleus noradrenergic system on odor recognition in the mouse. Mice exposed to a nonrewarded olfactory stimulation (training) were able to memorize this odor and to discriminate it from a new odor in a recall test performed 15 min later. At longer delays (30 or 60 min), the familiar odor was no longer retained, and both stimuli were perceived as new ones. Following a post-training injection of the alpha(2)-adrenoceptor antagonist dexefaroxan, the familiar odor was still remembered 30 min after training. In contrast, both the alpha(2)-adrenoceptor agonist UK 14304 and the noradrenergic neurotoxin DSP-4 prevented the recognition of the familiar odor 15 min after the first exposure. Noradrenaline release in the olfactory bulb, assessed by measurement of the extracellular noradrenaline metabolite normetanephrine, was increased by 62% following dexefaroxan injection, and was decreased by 38%-44% after treatment with UK 14304 and DSP-4. Performance of mice in the recall test was reduced by a post-training injection of the beta-adrenoceptor antagonist propranolol or the alpha(1)-antagonist prazosin, thus implicating a role for beta- and alpha(1)-adrenoceptors in the facilitating effects of noradrenaline on short-term olfactory recognition in this model.     

Olfactory working memory: effects of verbalization on the 2-back task

Working memory for odors, which has received almost no attention in the literature, was investigated in two experiments. We show that performance in a 2-back task with odor stimuli is well above chance. This is true not only for highly familiar odors, as has been shown by Dade, Zatorre, Evans, and Jones-Gotman, NeuroImage, 14, 650–660, (2001), but also for unfamiliar ones that are notoriously difficult to name. We can conclude that information about an olfactory stimulus can be retained in the short term and can continuously be updated for comparison with new olfactory probes along the lines of a functional odor working memory. However, the performance in the working memory task is highly dependent on participants’ verbalization of the odor. In addition, results indicated that odor working memory performance is dependent on the ability to discriminate among the odor stimuli (Experiment 2). The results are discussed in relation to recent ideas of a separate olfactory working memory slave system.     

A procedure for obtaining young children’s reports of olfactory stimuli

Young children (ages 2 to 5) have proved to be difficult subjects for obtaining valid reports of their ratings of olfactory stimuli. Thirty-six preschoolers were tested on benzaldehyde (a pleasant odor) and on dimethyl disulfide (an unpleasant odor) using a smiling or frowning face as a response format. The results showed the ability of young children to discriminate between pleasant and unpleasant odors.     

Neural correlates of olfactory learning: Critical role of centrifugal neuromodulation

The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of plasticity. As in other sensory systems, this plasticity can be controlled by centrifugal inputs from brain regions known to be involved in attention and learning processes. Specifically, both the bulb and cortex receive heavy inputs from cholinergic, noradrenergic, and serotonergic modulatory systems. These neuromodulators are shown to have profound effects on both odor processing and odor memory by acting on both inhibitory local interneurons and output neurons in both regions.     

Effects of social isolation in adulthood on odor preferences and urine-marking in male rats

Male rats isolated for 60 days in adulthood spent less time investigating odors of females and urine-marked less over these odors than did males kept in groups of three. Isolated males did not differ from grouped males in their responses to odors of unfamiliar males or their own odors. After social experience the isolated males showed an increase in urine-marking but no change in odor preferences. Individual housing therefore appears to alter olfactory communication in the same way that it does other social behaviors and these changes may be mediated by the same mechanisms.     

Acetylcholine and olfactory perceptual learning

Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform cortex. These changes include enhanced representation of the molecular features of familiar odors by mitral cells in the olfactory bulb, and synthetic coding of multiple coincident odorant features into odor objects by cortical neurons. In this paper, data are reviewed that show the critical role of acetylcholine (Ach) in olfactory system function and plasticity, and cholinergic modulation of olfactory perceptual learning at both the behavioral and cortical level.     

Short-term contact elicits heterospecific behavioral discrimination of individual odors in mound-building mice (Mus spicilegus)

The authors used a habituation-dishabituation procedure to test the ability of male mound-building mice (Mus spicilegus) to discriminate individual odors from males of another species of mouse. Male mound-building mice failed to spontaneously discriminate individual odors from Mus musculus musculus males, a natural competitor. After 24-hr contact with a male of one of the M. musculus subspecies (M. m. musculus or M. m. domesticus), experienced M. spicilegus males discriminated the individual odors of unfamiliar males of the same subspecies. These results confirm that discrimination of individual chemosignals is not confined to olfactory cues of a single species and provide new information about the effect of short-term contact on discrimination of individual odors across species.     

Olfactory predator recognition in predator-naïve gray mouse lemurs (Microcebus murinus)

Olfactory cues of predators, such as feces, are known to elicit antipredator responses in animals (e.g., avoidance, activity). To date, however, there is little information on olfactory predator recognition in primates. We tested whether the odor of feces of different predator categories (historical Malagasy predators and introduced predators) and of Malagasy nonpredators (control) induces antipredator behavior in captive born, predator-na?ve gray mouse lemurs. In an olfactory predator experiment a mouse lemur was exposed to a particular odor, fixed at a preferred location, where the animal was trained to get a reward. The behavior of the mouse lemur toward the respective stimulus category was videotaped and quantified. Results showed that mouse lemurs avoided the place of odor presentation when the odor belonged to a predator. They reacted with a significantly enhanced activity when exposed to odors of carnivores compared to those of nonpredatory controls. These findings are in favor of a genetic predisposition of olfactory predator recognition that might be based on the perception of metabolites from meat digestion.     

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.     

Differential regional expression of brain-derived neurotrophic factor following olfactory fear learning

We examined brain-derived neurotrophic factor (BDNF) mRNA expression across the olfactory system following fear conditioning. Mice received 10 pairings of odor with footshock or equivalent unpaired odors and shocks. We found increased BDNF mRNA in animals receiving paired footshocks in the multiple regions examined including the posterior piriform cortex (PPC) and basolateral amygdala (BLA). This was in contrast to the unpaired and odor-alone treatments, where BDNF mRNA was increased in the olfactory bulb (OB) and anterior piriform cortex (APC) only, but not the higher olfactory areas. We propose that odor exposure increases expression of BDNF in the OB and APC while the PPC and BLA increase BDNF mRNA only when associative learning occurs.     

Categorizing Smells: A Localist Approach

Humans are poorer at identifying smells and communicating about them, compared to other sensory domains. They also cannot easily organize odor sensations in a general conceptual space, where geometric distance could represent how similar or different all odors are. These two generalities are more or less accepted by psychologists, and they are often seen as connected: If there is no conceptual space for odors, then olfactory identification should indeed be poor. We propose here an important revision to this conclusion: We believe that the claim that there is no odor space is true only if by odor space, one means a conceptual space representing all possible odor sensations, in the paradigmatic sense used for instance for color. However, in a less paradigmatic sense, local conceptual spaces representing a given subset of odors do exist. Thus the absence of a global odor space does not warrant the conclusion that there is no olfactory conceptual map at all. Here we show how a localist account provides a new interpretation of experts and cross-cultural categorization studies: Rather than being exceptions to the poor olfactory identification and communication usually seen elsewhere, experts and cross-cultural categorization are here taken to corroborate the existence of local conceptual spaces.     

Paradoxical olfactory function in combat Veterans: The role of PTSD and odor factors

Stress- and trauma-related disorders, including posttraumatic stress disorder (PTSD), are characterized by an increased sensitivity to threat cues. Given that threat detection is a critical function of olfaction and that combat trauma is commonly associated with burning odors, we sought a better understanding of general olfactory function as well as response to specific trauma-related (i.e. burning) odors in combat-related PTSD. Trauma-exposed combat Veterans with (n = 22) and without (n = 25) PTSD were assessed for general and specific odor sensitivities using a variety of tools. Both groups had similar general odor detection thresholds. However, the combat Veterans with PTSD, compared to combat Veterans with comparable trauma exposure but without PTSD, had increased ratings of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with a blunted heart rate in response to burning rubber odor. These findings are discussed within the context of healthy versus pathological changes in olfactory processing that occur over time after psychological trauma.     

The hippocampus and memory for "what," "where," and "when"

Previous studies have indicated that nonhuman animals might have a capacity for episodic-like recall reflected in memory for "what" events that happened "where" and "when". These studies did not identify the brain structures that are critical to this capacity. Here we trained rats to remember single training episodes, each composed of a series of odors presented in different places on an open field. Additional assessments examined the individual contributions of odor and spatial cues to judgments about the order of events. The results indicated that normal rats used a combination of spatial ("where") and olfactory ("what") cues to distinguish "when" events occurred. Rats with lesions of the hippocampus failed in using combinations of spatial and olfactory cues, even as evidence from probe tests and initial sampling behavior indicated spared capacities for perception of spatial and odor cues, as well as some form of memory for those individual cues. These findings indicate that rats integrate "what," "where," and "when" information in memory for single experiences, and that the hippocampus is critical to this capacity.     

Age-related changes in discrimination of unfamiliar odors

If odor perception involves mnemonic processes, differences in olfactory experience should affect discriminative ability. This was examined here by comparing discriminative performance in children and adults. Using an oddity test of discrimination, in Experiment 1 we tested 6-year-olds (G1), 11-year-olds (G6), and adults (A) on their ability to discriminate unfamiliar odors that varied either in quality (Q) or in quality and intensity (QI). G1 participants were poorer at discriminating the QI set, relative to G6 and A. In Experiment 2, we used an analogous visual procedure and confirmed that this age-related difference was olfactory specific. In Experiment 3, we repeated Experiment 1 but used an articulatory suppression task. G1 participants were poorer than G6 and A participants for both the Q and the QI sets. The implications of these findings for experiential accounts of odor perception and olfactory working memory are discussed.     

Opposing effects on muscarinic acetylcholine receptors in the piriform cortex of odor-trained rats

We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm (“rule learning”). It has been reported that at 1–3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current I_AHP, which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the I_AHP in neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3–8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training.     

Odors Can Serve as Landmarks in Human Wayfinding

Scientists have shown that many non‐human animals such as ants, dogs, or rats are very good at using smells to find their way through their environments. But are humans also capable of navigating through their environment based on olfactory cues? There is not much research on this topic, a gap that the present research seeks to bridge. We here provide one of the first empirical studies investigating the possibility of using olfactory cues as landmarks in human wayfinding. Forty subjects participated in a piloting study to determine the olfactory material for the main experiment. Then, 24 subjects completed a wayfinding experiment with 12 odors as orientation cues. Our results are astonishing: Participants were rather good at what we call “odor‐based wayfinding.” This indicates that the ability of humans to use olfactory cues for navigation is often underestimated. We discuss two different cognitive explanations and rule out the idea that our results are just an instance of sequential learning. Rather, we argue that humans can enrich their cognitive map of the environment with olfactory landmarks and may use them for wayfinding.