Topological reorganization of odor representations in the olfactory bulb

Odors are initially represented in the olfactory bulb (OB) by patterns of sensory input across the array of glomeruli. Although activated glomeruli are often widely distributed, glomeruli responding to stimuli sharing molecular features tend to be loosely clustered and thus establish a fractured chemotopic map. Neuronal circuits in the OB transform glomerular patterns of sensory input into spatiotemporal patterns of output activity and thereby extract information about a stimulus. It is, however, unknown whether the chemotopic spatial organization of glomerular inputs is maintained during these computations. To explore this issue, we measured spatiotemporal patterns of odor-evoked activity across thousands of individual neurons in the zebrafish OB by temporally deconvolved two-photon Ca²⁺ imaging. Mitral cells and interneurons were distinguished by transgenic markers and exhibited different response selectivities. Shortly after response onset, activity patterns exhibited foci of activity associated with certain chemical features throughout all layers. During the subsequent few hundred milliseconds, however, MC activity was locally sparsened within the initial foci in an odor-specific manner. As a consequence, chemotopic maps disappeared and activity patterns became more informative about precise odor identity. Hence, chemotopic maps of glomerular input activity are initially transmitted to OB outputs, but not maintained during pattern processing. Nevertheless, transient chemotopic maps may support neuronal computations by establishing important synaptic interactions within the circuit. These results provide insights into the functional topology of neural activity patterns and its potential role in circuit function.     

Spatio-temporal dynamics of odor representations in the mammalian olfactory bulb

We explored the spatio-temporal dynamics of odor-evoked activity in the rat and mouse main olfactory bulb (MOB) using voltage-sensitive dye imaging (VSDI) with a new probe. The high temporal resolution of VSDI revealed odor-specific sequences of glomerular activation. Increasing odor concentrations reduced response latencies, increased response amplitudes, and recruited new glomerular units. However, the sequence of glomerular activation was maintained. Furthermore, we found distributed MOB activity locked to the nasal respiration cycle. The spatial distribution of its amplitude and phase was heterogeneous and changed by sensory input in an odor-specific manner. Our data show that in the mammalian olfactory bulb, odor identity and concentration are represented by spatio-temporal patterns, rather than spatial patterns alone.     

Patterned response to odor in single neurones of goldfish olfactory bulb: influence of odor quality and other stimulus parameters

Responses of 75 single units in the goldfish olfactory bulb were analyzed in detail for their relationship to the time-course of the change in odor concentration during each odor stimulus. Odor stimuli were controlled for rise time, duration, and peak concentration by an apparatus developed for the purpose. This apparatus enabled aqueous odor stimuli to be interposed into a constant water stream without changes in flow rate. The time-course of the concentration change within the olfactory sac was inferred from conductivity measurements at the incurrent and excurrent nostrils. Temporal patterns of firing rate elicited by stimuli with relatively slow rising and falling phases could be quite complex combinations of excitation and suppression. Different temporal patterns were produced by different substances at a single concentration in most units. Statistical measures of the temporal pattern of response for a small number of cells at a given concentration were more characteristic of the stimulus substance than any of three measures of magnitude of response. The temporal patterns change when the peak concentration, duration, and rise time of the stimuli are varied. The nature of these changes suggests that the different patterns are due primarily to the combined influence of two factors: (a) a stimulus whose concentration varies over time and (b) a relationship between concentration and impulse frequency which varies from unit to unit. Some units produce patterns suggestive of influence by neural events of long time constant. The importance of temporal patterns in odor quality and odor intensity coding is discussed.     

Robust odor coding via inhalation-coupled transient activity in the mammalian olfactory bulb

It has been proposed that a single sniff generates a snapshot of the olfactory world. However, odor coding on this timescale is poorly understood, and it is not known whether coding is invariant to changes in respiration frequency. We investigated this by recording spike trains from the olfactory bulb in awake, behaving rats. During rapid sniffing, odor inhalation triggered rapid and reliable cell- and odor-specific temporal spike patterns. These fine temporal responses conveyed substantial odor information within the first ～100 ms, and correlated with behavioral discrimination time on a trial-by-trial basis. Surprisingly, the initial transient portions of responses were highly conserved between rapid sniffing and slow breathing. Firing rates over the entire respiration cycle carried less odor information, did not correlate with behavior, and were poorly conserved across respiration frequency. These results suggest that inhalation-coupled transient activity forms a robust neural code that is invariant to changes in respiration behavior.     

Effects of olfactory peduncle sectioning on the single unit responses of olfactory bulb neurons to odor presentation in awake rabbits

The influences of centrifugal inputs to the olfactory bulb werestudied by recording singlecell responses evoked by olfactorystimuli in intact and peduncle-sectioned bulbs of awake freebreathingrabbits. Responses of intact animals were mainly characterizedby a temporal reorganization of the single unit discharge -responsive second order neurons increased their firing activityduring inspirations and were silent during expirations. Thissynchronization of firing discharge with respiration occurredin the absence of any significant change in the overall firingactivity measured over intervals which included both the inspiratoryand expiratory phases of the respiratory cycle. By contrast,neurons recorded in isolated olfactory bulbs exhibited eithera significant increase or a decrease in firing activity duringodor presentation, and, furthermore, the synchronization ofthese units to the respiratory cycle was markedly reduced comparedwith that in intact animals. Comparison of cell responsivenessbetween intact and isolated olfactory bulbs indicated that thelesion increased the number of odors which induced a response,but did not change the percentage of cells which failed to respondto any of the 5 odorants used in this study. The cell responsivenessincreased for camphor and isoamyl acetate, and to a lesser extentfor food odor. The results indicate that high order nervousstructures exert a powerful inhibitory influence on the responsesof olfactory bulb second-order neurons to odor stimuli. Theyalso suggest that, in intact rabbits, centrifugal inputs playa role in the odor-induced synchronization of the single unitactivity with respiration.     

A model of olfactory adaptation and sensitivity enhancement in the olfactory bulb

It has been suggested that the olfactory bulb, the first processing center after the sensory cells in the olfactory pathway, plays a role in olfactory adaptation, odor sensitivity enhancement by motivation and other olfactory psychophysical phenomena. In a mathematical model based on the bulbar anatomy and physiology, the inputs from the higher olfactory centers to the inhibitory cells in the bulb are shown to be able to modulate the response, and thus the sensitivity of the bulb to specific odor inputs. It follows that the bulb can decrease its sensitivity to a pre-existing and detected odor (adaptation) while remaining sensitive to new odors, or increase its sensitivity to interested searching odors. Other olfactory psychophysical phenomena such as cross-adaptation etc. are discussed as well.     

A neural mechanism of hierarchical discrimination of odors in the olfactory cortex based on spatiotemporal encoding of odor information

We propose a neural mechanism for discrimination of different complex odors in the olfactory cortex based on the dynamical encoding scheme. Both constituent molecules of the odor and their mixing ratios are encoded simultaneously into a spatiotemporal activity pattern (limit cycle attractor) in the olfactory bulb [Hoshino O, Kashimori Y, Kambara T (1998) Biol Cybern 79:109–120]. We present a functional model of the olfactory cortex consisting of some dynamical mapping modules. Each dynamical map is represented by itinerancy among the limit cycle attractors. When a temporal sequence of spatial activity patterns corresponding to a complex odor is injected from the bulb to the network of the olfactory cortex, the neural activity state of each mapping module is fixed to a relevant spatial pattern injected. Recognition of an odor is accomplished by a combination of firing patterns fixed in all the mapping modules. The stronger the response strength of the component, the earlier the component is recognized. The hierarchical discrimination of an odor is made by recognizing the components in order of decreasing response strengths. Received: 28 November 1998 / Accepted in revised form: 17 December 1999     

Rewiring the olfactory bulb: changes in odor maps following recovery from nerve transection

Recent studies have shown that axons from olfactory receptor subtypes converge onto glomeruli in fixed positions within the olfactory bulb. Different receptor subtypes project to different glomeruli, forming a spatial distribution of odor information or 'odor maps'. Olfactory receptor neurons are continuously replaced throughout the life span of an animal, yet they preserve this highly localized mapping of receptor subtypes. In this study we used a transgenic mouse (P2-IRES-tau-lacZ) to map axons from a single receptor subtype (P2 receptors) in order to determine if regenerating axons were able to re-establish the P2 receptor map following nerve transection. Results confirm that P2 receptor axons retain their capacity to grow back to the olfactory bulb and converge onto glomeruli following nerve transection. However, the location and number of convergence sites was significantly altered compared to the control map. This change in the spatial distribution of axons alters the topography of odor mapping and has important implications for the processing of olfactory information. Findings from this study may explain why animals recovering from nerve injury require odor training before odor discrimination is restored. Future studies of olfactory receptor mapping could prove helpful in planning strategies to rewire connections in the brain and to restore function following injury or neurological disease.     

Orexin A effects on the olfactory bulb spontaneous activity and odor responsiveness in freely breathing rats

The mitral cells (MCs) of the olfactory bulb (OB) are relay neurons between the periphery and the central nervous structures. MCs receive in turn a centrifugal control from several higher brain centers that depends on the nutritional state. In this study, we investigated the effects of orexin A (ORX), a novel molecule known to regulate food intake and whose receptors are present in the OB, on the electrophysiological activity of single MCs. Using icv-injections and direct applications on the OB, we determined the respective central and local effects of this molecule on the MCs' spontaneous firing activity and responsiveness to different odors. Icv-injections and local OB-applications were found to induce a significant decrease in spontaneous firing activity in 14% and 50% of the recorded MCs, respectively. In one case, ORX application on the OB caused a significant firing increase. Effects of OB-applications had shorter delays. The responsiveness of some MCs to food and non-food odors was also changed, but the proportion of changes was not statistically significant. Icv-injection effects likely resulted from a local action of ORX on the OB. Changes of spontaneous firing activity and odor responsiveness are discussed in terms of regulation of the functioning of the olfactory system.     

Olfactory bulb serotonin level modulates olfactory recognition in the neonate rat

Role of serotonin in olfactory recognition was tested by depleting the olfactory bulb serotonin during postnatal day (PND) 1 - 4 following administration of 5,7-dihydroxytryptamine. Significant difference in the olfactory recognition test was observed during PND5-7; control pups successfully recognized and oriented towards their mother; whereas treated pups failed to recognize their mother odour. Later on, during PND12-14, both group of pups responded equally in the recognition test. Levels of olfactory bulb serotonin were depleted (53.3%) in the treated pups on PND-8, which was restored on PND-14 with only 15% variation. Further analysis demonstrated that depletion of serotonin in olfactory bulb did not affect the normal suckling and weight gain, it only modulates olfactory recognition.     

Functional activity of the rat olfactory bulb related to different durations of odor exposure

We have studied the effects of different odor exposure durationson the functional activity of the rat olfactory bulb by usingthe 2-deoxyglucose (2-DG) method. This technique brings outodor-specific patterns of labeling in the glomerular layer ofthe bulb. In a first set of experiments, rats designated ascontrols were submitted to two stimulation conditions with cyclohexanonefor 40 min following 2-DG injection: group C-5—alternatestimulation (5 min odor–5 mm pure air); group C-20—continuousstimulation (20 mm odor-20 min pure air). In a second set ofexperiments, rats designated as ‘adapted’ were exposedfor 3 h to cyclohexanone before the 2-DG injection; then, threeconditions of stimulation were tested with the same odor duringthe post-injection period; group Adap-5—alternate stimulation;group Adap-20—continuous stimulation; group Adap-0—stimulationwith pure air only. In the two control groups, the total numbersof labeled glomerular foci were similar; however, group C-20showed a significant increase in the number of ‘heavily’labeled foci. This result suggests that under conditions of20 min continuous odor exposure, receptor cells do not adaptrapidly and totally. Results from the adapted groups showedthat only the group Adap-20 presented significant changes infunctional bulbar activity. An important decrease in the totalnumber of labeled glomerular foci and an absence of ‘heavily’labeled foci were noted in all rats of this group; their patternsof 2-DG uptake were greatly reduced in both complexity and contrast.These results highlight the importance of olfactory receptoradaptation under conditions of long-duration odor exposure.Fast recovery of receptor sensitivity when the stimulation isinterrupted is also suggested.     

Self-organization in the olfactory system: one shot odor recognition in insects

We show in a model of spiking neurons that synaptic plasticity in the mushroom bodies in combination with the general fan-in, fan-out properties of the early processing layers of the olfactory system might be sufficient to account for its efficient recognition of odors. For a large variety of initial conditions the model system consistently finds a working solution without any fine-tuning, and is, therefore, inherently robust. We demonstrate that gain control through the known feedforward inhibition of lateral horn interneurons increases the capacity of the system but is not essential for its general function. We also predict an upper limit for the number of odor classes Drosophila can discriminate based on the number and connectivity of its olfactory neurons. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

High-resolution analysis of the spatio-temporal activity patterns in rat olfactory bulb evoked by enantiomer odors

Understanding how mammals process olfactory stimuli has motivated the development of tools and techniques which permit the simultaneous study of finely structured spatial and temporal patterns of neural activity. A technique is described that uses an array of 32 penetrating microelectrodes implanted bilaterally into the dorsal aspect of rat olfactory bulb to investigate the responses of mitral and tufted neurons to stimulation with simple enantiomer odor pairs at a number of concentrations. It is shown that stable, simultaneous recordings from up to 49 single- and multi-units can be performed for periods of up to 14 h. We show that such odors evoke unique spatial and fast-temporal activity patterns which may subserve odor discrimination. This technique is extensible to other systems neuroscience investigations of olfactory sensory processing.     

Dynamic ensemble odor coding in the mammalian olfactory bulb: sensory information at different timescales

Neural firing discharges are often temporally patterned, but it is often ambiguous as to whether the temporal features of these patterns constitute a useful code. Here we show in the mouse olfactory bulb that ensembles of projection neurons respond with complex odor- and concentration-specific dynamic activity sequences developing below and above sniffing frequency. Based on this activity, almost optimal discrimination of presented odors was possible during single sniffs, consistent with reported behavioral data. Within a sniff cycle, slower features of the dynamics alone (>100 ms resolution, including mean firing rate) were sufficient for maximal discrimination. A smaller amount of information was also observed in faster features down to 20-40 ms resolution. Therefore, mitral cell ensemble activity contains information at different timescales that could be separately or complementarily exploited by downstream brain centers to make odor discriminations. Our results also support suggestive analogies in the dynamics of odor representations between insects and mammals.     

Reaction time for the recognition of odor quality

Psychophysical procedures were used to determine human recognitiontimes to three matched intensity levels of the odorants n-butanol,(+)-limonene and propionic acid. A computer controlled the deliveryof the odorants from an air dilution olfactometer and measuredrecognition times. The mean times recorded with the odorantswere significantly different and ranged between 680–867ms, the shortest times being recorded with the acid. The resultsare discussed in relation to reported detection and recognitiontimes, and their relevance to odor mixture perception, in particularit was concluded that reaction times for recognition do notpredict the occurrence of suppression in mixtures.     

The olfactory subgenome and specific odor recognition in forest musk deer

Olfactory receptors (ORs) are encoded by OR genes. The OR genes in forest musk deer (Moschus berezovskii), which rely on olfaction for reproductive and social communication, are poorly understood. In this study, we analyzed the genome sequence of the forest musk deer to obtain its olfactory subgenome and compared it to other species. A total of 1378 OR‐related sequences were detected in the forest musk deer genome including 864 functional genes, 366 pseudogenes and 148 partial genes. These OR genes were classified into Class I and Class II and were further classified into 18 families and 244 subfamilies through sequence identity. Comparative analyses of the OR genes’ protein sequences in species from different orders (forest musk deer, human, mouse and dog) showed that 12 clusters were specific to forest musk deer. However, when compared to other Artiodactyl species (i.e. cattle, yak and pig) only two clusters were specific to forest musk deer. The odor identification potential of the OR genes in the forest musk deer was focused mainly on floral, woody, lemon, sweet and fatty odors. We also found that OR genes specific to forest musk deer were involved in the identification of spearmint and caraway. Our work is the first genome‐wide analysis of OR genes in forest musk deer. These findings will assist with better understanding the relationship between behavior and olfaction in the forest musk deer and the characteristics of the olfactory subgenome in Artiodactyl mammals.     

尿液气味刺激后棕色田鼠主嗅球和副嗅球的神经元活动

本实验利用免疫组织化学方法,以FOS阳性反应作为神经元活动的标志,研究了棕色田鼠在受到同性和异性尿液刺激后主嗅球和副嗅球的神经元活动,表明两大嗅觉系统均有感知社会性化学信号的功能.通过比较棕色田鼠在同性和异性尿液刺激后副嗅球和主嗅球的嗅小球细胞层(GL)、僧帽细胞层(MIT)、颗粒细胞层(GRL)中FOS阳性神经元数量,发现不同性别尿液刺激后棕色田鼠的副嗅球各细胞层FOS阳性神经元数量比对照组明显增加;棕色田鼠受到异性尿液刺激后其副嗅球各细胞层的FOS阳性神经元数量均多于同性尿液刺激组.不同性别尿液刺激后棕色田鼠的主嗅球各细胞层FOS阳性神经元数量相较于对照组有增加或增加显著;异性尿液刺激组主嗅球各细胞层的FOS阳性神经元数量均多于同性尿液刺激组.说明棕色田鼠的副嗅球和主嗅球均参与了通过尿液介导的性别个体的识别.     

Neurogenesis drives stimulus decorrelation in a model of the olfactory bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb – the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells – are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures.