Odor Encoding Research Articles

Bimodal odor processing with a trigeminal component at sub- and suprathreshold levels

Odors are typically bimodal in nature, interacting with the olfactory and trigeminal systems. The trigeminal component may be noticed (e.g. menthol) or perceptually ignored, leading to different neural substrates being recruited during odor encoding. Therefore, the current study was designed to explore the perceptual and central-nervous activations in response to pleasant bimodal odors using functional magnetic resonance imaging (fMRI). In this study, healthy subjects were exposed to odorants alone (unimodal) or with a “cooling” trigeminal component (bimodal) at sub- and suprathreshold concentrations with a portable olfactometer in a 3T fMRI scanner. Within the scanner, subjects reported all odorants as pleasant and intensity increasing with trigeminal concentration. Many of the regions of interest [orbital frontal cortex (OFC), insula, thalamus, cerebellum, postcentral gyrus and cingulate cortex] were activated during bimodal odor conditions when contrasted with unimodal, and interestingly, most of these activations were seen prior to trigeminal perception (e.g. at a sub-threshold level). This includes large bilateral activations within the OFC, insula, cerebellum and parts of the cingulate cortex. Additionally, activation of the thalamus was seen early in the stages of bimodal odor encoding suggesting its role of mediating attention toward the presence of two stimuli. Lastly, intensity encoding during bimodal processing shows overlap of previously demonstrated simple trigeminal encoding areas (medial cingulate cortex) and the more complex olfactory encoding areas (bilateral insula, superior temporal gyrus, OFC, and cerebellum), but not the amygdala.

Neural Encoding of Odors during Active Sampling and in Turbulent Plumes

Sensory inputs are often fluctuating and intermittent, yet animals reliably utilize them to direct behavior. Here we ask how natural stimulus fluctuations influence the dynamic neural encoding of odors. Using the locust olfactory system, we isolated two main causes of odor intermittency: chaotic odor plumes and active sampling behaviors. Despite their irregularity, chaotic odor plumes still drove dynamic neural response features including the synchronization, temporal patterning, and short-term plasticity of spiking in projection neurons, enabling classifier-based stimulus identification and activating downstream decoders (Kenyon cells). Locusts can also impose odor intermittency through active sampling movements with their unrestrained antennae. Odors triggered immediate, spatially targeted antennal scanning that, paradoxically, weakened individual neural responses. However, these frequent but weaker responses were highly informative about stimulus location. Thus, not only are odor-elicited dynamic neural responses compatible with natural stimulus fluctuations and important for stimulus identification, but locusts actively increase intermittency, possibly to improve stimulus localization.

Simultaneous Encoding of Odors by Channels with Diverse Sensitivity to Inhibition

Odorant receptors in the periphery map precisely onto olfactory glomeruli ("coding channels") in the brain. However, the odor tuning of a glomerulus is not strongly correlated with its spatial position. This raises the question of whether lateral inhibition between glomeruli is specific or nonspecific. Here we show that, in the Drosophila brain, focal activation of even a single glomerulus recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of interneuron activity in different glomeruli is largely odor invariant. Although interneurons are recruited nonspecifically, glomeruli differ dramatically in their sensitivity to interneuron activity, and this is explained by their varying sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel by channels having high and low sensitivity to inhibition. Because lateral inhibition confers both costs and benefits, the brain might rely preferentially on "high" and "low" channels in different behavioral contexts.

Spiking Irregularity and Frequency Modulate the Behavioral Report of Single-Neuron Stimulation

The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning.

Chapter 1 - Olfactory Habituation in Drosophila—Odor Encoding and its Plasticity in the Antennal Lobe

A ubiquitous feature of an animal's response to an odorant is that it declines when the odorant is frequently or continuously encountered. This decline in olfactory response, termed olfactory habituation, can have temporally or mechanistically different forms. The neural circuitry of the fruit fly Drosophila melanogaster's olfactory system is well defined in terms of component cells, which are readily accessible to functional studies and genetic manipulation. This makes it a particularly useful preparation for the investigation of olfactory habituation. In addition, the insect olfactory system shares many architectural and functional similarities with mammalian olfactory systems, suggesting that olfactory mechanisms in insects may be broadly relevant. In this chapter, we discuss the likely mechanisms of olfactory habituation in context of the participating cell types, their connectivity, and their roles in sensory processing. We overview the structure and function of key cell types, the mechanisms that stimulate them, and how they transduce and process odor signals. We then consider how each stage of olfactory processing could potentially contribute to behavioral habituation. After this, we overview a variety of recent mechanistic studies that point to an important role for potentiation of inhibitory synapses in the primary olfactory processing center, the antennal lobe, in driving the reduced response to familiar odorants. Following the discussion of mechanisms for short- and long-term olfactory habituation, we end by considering how these mechanisms may be regulated by neuromodulators, which likely play key roles in the induction, gating, or suppression of habituated behavior, and speculate on the relevance of these processes for other forms of learning and memory.

Mechanisms of Odor Coding in Coniferous Bark Beetles: From Neuron to Behavior and Application

Coniferous bark beetles (Coleoptera: Curculionidae: Scolytinae) locate their hosts by means of olfactory signals, such as pheromone, host, and nonhost compounds. Behavioral responses to these volatiles are well documented. However, apart from the olfactory receptor neurons (ORNs) detecting pheromones, information on the peripheral olfactory physiology has for a long time been limited. Recently, however, comprehensive studies on the ORNs of the spruce bark beetle,Ips typographus, were conducted. Several new classes of ORNs were described and odor encoding mechanisms were investigated. In particular, links between behavioral responses and ORN responses were established, allowing for a more profound understanding of bark beetle olfaction. This paper reviews the physiology of bark beetle ORNs. Special focus is onI. typographus, for which the available physiological data can be put into a behavioral context. In addition, some recent field studies and possible applications, related to the physiological studies, are summarized and discussed.

Olfactory Coding: Giant Inhibitory Neuron Governs Sparse Odor Codes

Electrophysiological investigations in locusts have revealed that the sparseness of odor representations, in the brain region expected to mediate olfactory learning, is shaped by a unique inhibitory neuron.

Normalization for sparse encoding of odors by a wide-field interneuron.

Sparse coding presents practical advantages for sensory representations and memory storage. In the insect olfactory system, the representation of general odors is dense in the antennal lobes but sparse in the mushroom bodies, only one synapse downstream. In locusts, this transformation relies on the oscillatory structure of antennal lobe output, feed-forward inhibitory circuits, intrinsic properties of mushroom body neurons, and connectivity between antennal lobe and mushroom bodies. Here we show the existence of a normalizing negative-feedback loop within the mushroom body to maintain sparse output over a wide range of input conditions. This loop consists of an identifiable "giant" nonspiking inhibitory interneuron with ubiquitous connectivity and graded release properties.

Olfactory Coding with Patterns of Response Latencies

The encoding of odors by spatiotemporal patterns of mitral/tufted (M/T) cells in the vertebrate olfactory bulb has been discussed controversially. Motivated by temporal constraints from behavioral studies, we investigated the information contained in odor-evoked first-spike latencies. Using simultaneous recordings of dozens of M/T cells with a high temporal resolution and quantitative ensemble correlation techniques, we show that latency patterns, and in particular latency rank patterns, are highly odor specific and reproducible. They reliably predict the odor identity as well as the odor concentration on a single-trial basis and on short timescales-in fact, more reliably than patterns of firing rates. Furthermore, we show that latency ranks exhibit a better reproducibility at the level of M/T cells than in olfactory receptor neurons. Our results suggest that the latency patterns of M/T cells contain all the information higher brain centers need to identify odors and their concentrations.

Olfactory Coding with Patterns of Response Latencies

The encoding of odors by spatiotemporal patterns of mitral/tufted (M/T) cells in the vertebrate olfactory bulb has been discussed controversially. Motivated by temporal constraints from behavioral studies, we investigated the information contained in odor-evoked first-spike latencies. Using simultaneous recordings of dozens of M/T cells with a high temporal resolution and quantitative ensemble correlation techniques, we show that latency patterns, and in particular latency rank patterns, are highly odor specific and reproducible. They reliably predict the odor identity as well as the odor concentration on a single-trial basis and on short timescales-in fact, more reliably than patterns of firing rates. Furthermore, we show that latency ranks exhibit a better reproducibility at the level of M/T cells than in olfactory receptor neurons. Our results suggest that the latency patterns of M/T cells contain all the information higher brain centers need to identify odors and their concentrations.

Synaptic Inhibition in the Olfactory Bulb Accelerates Odor Discrimination in Mice

Local inhibitory circuits are thought to shape neuronal information processing in the central nervous system, but it remains unclear how specific properties of inhibitory neuronal interactions translate into behavioral performance. In the olfactory bulb, inhibition of mitral/tufted cells via granule cells may contribute to odor discrimination behavior by refining neuronal representations of odors. Here we show that selective deletion of the AMPA receptor subunit GluA2 in granule cells boosted synaptic Ca(2+) influx, increasing inhibition of mitral cells. On a behavioral level, discrimination of similar odor mixtures was accelerated while leaving learning and memory unaffected. In contrast, selective removal of NMDA receptors in granule cells slowed discrimination of similar odors. Our results demonstrate that inhibition of mitral cells controlled by granule cell glutamate receptors results in fast and accurate discrimination of similar odors. Thus, spatiotemporally defined molecular perturbations of olfactory bulb granule cells directly link stimulus similarity, neuronal processing time, and discrimination behavior to synaptic inhibition.

Pheromone Transduction in Moths

Calling female moths attract their mates late at night with intermittent release of a species-specific sex-pheromone blend. Mean frequency of pheromone filaments encodes distance to the calling female. In their zig-zagging upwind search male moths encounter turbulent pheromone blend filaments at highly variable concentrations and frequencies. The male moth antennae are delicately designed to detect and distinguish even traces of these sex pheromones amongst the abundance of other odors. Its olfactory receptor neurons sense even single pheromone molecules and track intermittent pheromone filaments of highly variable frequencies up to about 30 Hz over a wide concentration range. In the hawkmoth Manduca sexta brief, weak pheromone stimuli as encountered during flight are detected via a metabotropic PLCβ-dependent signal transduction cascade which leads to transient changes in intracellular Ca2+ concentrations. Strong or long pheromone stimuli, which are possibly perceived in direct contact with the female, activate receptor-guanylyl cyclases causing long-term adaptation. In addition, depending on endogenous rhythms of the moth's physiological state, hormones such as the stress hormone octopamine modulate second messenger levels in sensory neurons. High octopamine levels during the activity phase maximize temporal resolution cAMP-dependently as a prerequisite to mate location. Thus, I suggest that sliding adjustment of odor response threshold and kinetics is based upon relative concentration ratios of intracellular Ca2+ and cyclic nucleotide levels which gate different ion channels synergistically. In addition, I propose a new hypothesis for the cyclic nucleotide-dependent ion channel formed by insect olfactory receptor/coreceptor complexes. Instead of being employed for an ionotropic mechanism of odor detection it is proposed to control subthreshold membrane potential oscillation of sensory neurons, as a basis for temporal encoding of odors.

Fast and dynamic odor encoding in rat olfactory cortex during odor discrimination task

Event Abstract Back to Event Fast and dynamic odor encoding in rat olfactory cortex during odor discrimination task Active movement of sensory organs plays an important role in many sensory modalities. In olfaction, animals sniffing frequency shifts dynamically depending on animals? behavioral states or task demands. Previous behavioral studies from our group showed that rats can achieve highly accurate odor discrimination with a single sniff, suggesting that sniffing is a unit of odor encoding (Uchida and Mainen, 2003). However, very little is known about how active sniffing affects odor encoding by neurons, because most neurophysiological studies in mammalian olfaction have been performed in anesthetized animals. In this study, we wished to address how odor representations develop over sniff cycles and how these representations relate to behavioral performance. We focused on the olfactory cortex because it is closer to behavioral output than the olfactory bulb and therefore we expected that it may be easier to establish direct links between behavioral performance and neuronal activity. We recorded neural activity from individual cells in the anterior piriform cortex of rats using a multi-electrode recording technique while they performed a two-alternative odor discrimination task. The rats were trained to sample an odor at a central odor port and to go left or right to a choice port to obtain water rewards. In each session, at least six odors were used, with half of them assigned to either the left or right reward port. Simultaneously, respiration was monitored using a temperature sensor implanted in the nostril. Olfactory cortical neurons showed robust and transient odor responses with specific latencies that were tightly locked to sniff cycles. Many neurons showed odor-specific adaptation or facilitation at the second sniff. We then examined how the ensemble activity evolved across sniffs. Using principal component analysis, it could be seen that ensemble activity followed odor specific trajectories. Interestingly, the ensemble activity in the first sniff was significantly different from that in the second sniff. This contrasts with the highly similar trajectories repeated over multiple sniff cycles in previous studies in anesthetized animals. We next quantified information content within each sniff cycle by asking how well an ideal observer can discriminate six odors based on the neural activity. To do this we used several different pattern classification methods including support vector machines. This analysis showed that the discriminability of odors developed very rapidly within the first sniff and that the second sniff provided less information. Using the combined spikes during the first and second sniffs did not improve odor discriminability significantly compared to using only spike during the first sniff. In summary, an informative odor representation in the olfactory cortex of behaving rats appears to develop very rapidly within a single sniff and is not substantially augmented odor representation in the second sniff. These observations may help to explain the behavioral observation that multiple sniffs in the odor sampling port does not result in increased discrimination performance. This study suggests that olfactory processing during active sniffing favors rapid processing over prolonged temporal integration during an odor discrimination task.

Context effects on odor processing: An event-related potential study

The present study aimed to investigate the effects of cognitive/emotional bias on central nervous odor processing. Forty-five female participants were divided into three groups and were either led to believe the odor was a natural, healthy extract (positive bias), potentially hazardous (negative bias), or a common test odorant (control). The odor (isobornyl acetate) was presented via a constant-flow olfactometer and the EEG was recorded from 60 scalp locations. In the negative bias condition, participants reported reduced well-being and judged the odor as less pleasant. However, neither the thresholds nor the intensity ratings were changed by the context condition. Chemosensory event-related potential (CSERP) analysis revealed that the latencies of the N1 and P2 components were prolonged in the negative bias condition and shortened in the positive bias condition. Current source densities were most prominent in the frontal lobe in negatively biased participants. The findings show that expecting to perceive an emotionally significant odor affects the early encoding of odors.

Rapid Encoding and Perception of Novel Odors in the Rat

To gain insight into which parameters of neural activity are important in shaping the perception of odors, we combined a behavioral measure of odor perception with optical imaging of odor representations at the level of receptor neuron input to the rat olfactory bulb. Instead of the typical test of an animal's ability to discriminate two familiar odorants by exhibiting an operant response, we used a spontaneously expressed response to a novel odorant—exploratory sniffing—as a measure of odor perception. This assay allowed us to measure the speed with which rats perform spontaneous odor discriminations. With this paradigm, rats discriminated and began responding to a novel odorant in as little as 140 ms. This time is comparable to that measured in earlier studies using operant behavioral readouts after extensive training. In a subset of these trials, we simultaneously imaged receptor neuron input to the dorsal olfactory bulb with near-millisecond temporal resolution as the animal sampled and then responded to the novel odorant. The imaging data revealed that the bulk of the discrimination time can be attributed to the peripheral events underlying odorant detection: receptor input arrives at the olfactory bulb 100–150 ms after inhalation begins, leaving only 50–100 ms for central processing and response initiation. In most trials, odor discrimination had occurred even before the initial barrage of receptor neuron firing had ceased and before spatial maps of activity across glomeruli had fully developed. These results suggest a coding strategy in which the earliest-activated glomeruli play a major role in the initial perception of odor quality, and place constraints on coding and processing schemes based on simple changes in spike rate.

Expression and function of kainate receptors in the rat olfactory bulb

Although recent results suggest roles for NMDA and AMPA receptors in odor encoding, little is known about kainate receptors (KARs) in the olfactory bulb (OB). Molecular, immunological, and electrophysiological techniques were used to provide a functional analysis of KARs in the OB. Reverse transcriptase-polymerase chain reaction revealed that the relative level of expression of KAR subunits was GluR5 approximately GluR6 approximately KA2 > KA1 >> GluR7. In situ hybridization data imply that mitral/tufted cells express mostly GluR5 and KA2, whereas interneurons express mostly GluR6 and KA2. Immunohistochemical double-labeling experiments (GluR5/6/7 or GluR5 + synapsin) suggest that KARs are expressed at both synaptic and extrasynaptic loci. This heterogeneous expression of KAR subunits suggests that KARs may play a multitude of roles in odor processing, each tailored to the function of specific OB circuits. A functional analysis, using whole-cell electrophysiology, suggests that one such role is to increase the frequency of glutamate transmission while attenuating the amplitude of individual events, likely via a presynaptic depolarizing mechanism. Such effects would be important to odor processing particularly by OB glomeruli. In these highly compartmentalized structures, an increase in the frequency of glutamate release and the high density of extrasynaptic KARs, activated by spillover, could enhance glomerular synchronization and thus the transfer of more specific sensory information to cortical structures.

The neural representation of odor is modulated by the presence of a trigeminal stimulus during odor encoding

Objectives Odor perception does not simply consist in hierarchical processing from transduction to a single “true” cerebral representation. Odor sensation may be modulated by available sensory information during encoding. The present study set out to examine whether the presence of a pure trigeminal stimulus during odor encoding may modulate odor perception at both behavioral and cortical levels. Methods Participants were tested in a 2-session within-subject design: first, an odor encoding session included a delay conditioning procedure in which relatively selective olfactory stimulants (phenyl ethyl alcohol or vanillin, Conditioned Stimulus+, CS+) were presented either with a pulse of CO 2 (Unconditioned Stimulus, US), or alone (Conditioned Stimulus−, CS−); then, in the second session, both pure odorants (CS+ and CS−) were presented alone. During this second session, olfactory event-related potentials were simultaneously recorded and analyzed at different electrode sites including Cz and Pz (sites known to have maximal amplitudes for trigeminal and olfactory stimuli, respectively). After each trial, subjects were asked to rate odor intensity and hedonics. Results The results showed that CS+ intensity ratings increased in 8 subjects and decreased in 6. Cortically, a group effect was observed for P2 amplitude, which increased in the “CS+ intensity increase” group vs. the “CS+ intensity decrease” group at Cz ( p < 0.05) but not at Pz ( p > 0.05). Conclusions This result suggests that the presence of a pure trigeminal stimulus (CO 2) during odor encoding alters the neural representation of a pure odor. Significance The neural representation of odors comprises not only the odor itself but also contextual information (trigeminal in the present case) presented during encoding.

Oscillation and coding in a formal neural network considered as a guide for plausible simulations of the insect olfactory system

For the analysis of coding mechanisms in the insect olfactory system, a fully connected network of synchronously updated McCulloch and Pitts neurons (MC-P type) was developed [Quenet, B., Horn, D., 2003. The dynamic neural filter: a binary model of spatio-temporal coding. Neural Comput. 15 (2), 309–329]. Considering the update time as an intrinsic clock, this “Dynamic Neural Filter” (DNF), which maps regions of input space into spatio-temporal sequences of neuronal activity, is able to produce exact binary codes extracted from the synchronized activities recorded at the level of projection neurons (PN) in the locust antennal lobe (AL) in response to different odors [Wehr, M., Laurent, G., 1996. Odor encoding by temporal sequences of firing in oscillating neural assemblies. Nature 384, 162–166]. Here, in a first step, we separate the populations of PN and local inhibitory neurons (LN) and use the DNF as a guide for simulations based on biological plausible neurons (Hodgkin-Huxley: H-H type). We show that a parsimonious network of 10 H-H neurons generates action potentials whose timing represents the required codes. In a second step, we construct a new type of DNF in order to study the population dynamics when different delays are taken into account. We find synaptic matrices which lead to both the emergence of robust oscillations and spatio-temporal patterns, using a formal criterion, based on a Normalized Euclidian Distance (NED), in order to measure the use of the temporal dimension as a coding dimension by the DNF. Similarly to biological PN, the activity of excitatory neurons in the model can be both phase-locked to different cycles of oscillations which remind local field potential (LFP), and nevertheless exhibit dynamic behavior complex enough to be the basis of spatio-temporal codes.

Separate encoding of identity and similarity of complex familiar odors in piriform cortex

Piriform cortical circuits are hypothesized to form perceptions from responses to specific odorant features, but the anterior piriform cortex (aPCX) and posterior piriform cortex (pPCX) differ markedly in their anatomical organization, differences that could lead to distinct roles in odor encoding. Here, we tested whether experience with a complex odorant mixture would modify encoding of the mixture and its components in aPCX and pPCX. Rats were exposed to an odorant mixture and its components in a go/no-go rewarded odor discrimination task. After reaching behavioral performance criterion, single-unit recordings were made from the aPCX and pPCX in these rats and in odor-naïve, control, urethane-anesthetized rats. After odor experience, aPCX neurons were more narrowly tuned to the test odorants, and there was a decorrelation in aPCX population responses to the mixture and its components, suggesting a more distinct encoding of the familiar mixture from its components. In contrast, pPCX neurons were more broadly tuned to the familiar odorants, and pPCX population responses to the mixture and its components became more highly correlated, suggesting a pPCX encoding of similarity between familiar stimuli. The results suggest aPCX and pPCX play different roles in the processing of familiar odors and are consistent with an experience-dependent encoding (perceptual learning) of synthetic odorant identity in aPCX and an experience-dependent encoding of odor similarity or odor quality in pPCX.

Evidence for Ca2+-permeable AMPA receptors in the olfactory bulb

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), a subtype of glutamate receptor, contribute to olfactory processing in the olfactory bulb (OB). These ion channels consist of various combinations of the subunits GluR1-GluR4, which bestow certain properties. For example, AMPARs that lack GluR2 are highly permeable to Ca(2+) and generate inwardly rectifying currents. Because increased intracellular Ca(2+) could trigger a host of Ca(2+)-dependent odor-encoding processes, we used whole cell recording as well as histological and immunocytochemical (ICC) techniques to investigate whether AMPARs on rat OB neurons flux Ca(2+). Application of 1-naphthylacetyl spermine (NAS), a selective antagonist of Ca(2+)-permeable AMPARs (CP-AMPARs), inhibited AMPAR-mediated currents in subsets of interneurons and principal cells in cultures and slices. The addition of spermine to the electrode yielded inwardly rectifying current-voltage plots in some cells. In OB slices, olfactory nerve stimulation elicited excitatory responses in juxtaglomerular and mitral cells. Bath application of NAS with d,l-2-amino-5-phosphonovaleric acid (AP5) to isolate AMPARs suppressed the amplitudes of these synaptic responses compared with responses obtained using AP5 alone. Co(2+) staining, which involves the kainate-stimulated influx of Co(2+) through CP-AMPARs, produced diverse patterns of labeling in cultures and slices as did ICC techniques used with a GluR2-selective antibody. These results suggest that subsets of OB neurons express CP-AMPARs, including functional CP-AMPARs at synapses. Ca(2+) entry into cells via these receptors could influence odor encoding by modulating K(+) channels, N-methyl-d-aspartate receptors, and Ca(2+)-binding proteins, or it could facilitate synaptic vesicle fusion.