Odor representations in the rat olfactory bulb change smoothly with morphing stimuli

Many species of mammals are very good at categorizing odors. One model for how this is achieved involves the formation of "attractor" states in the olfactory processing pathway, which converge to stable representations for the odor. We analyzed the responses of rat olfactory bulb mitral/tufted (M/T) cells using stimuli "morphing" from one odor to another through intermediate mixtures. We then developed a phenomenological model for the representation of odors and mixtures by M/T cells and show that >80% of odorant responses to different concentrations and mixtures can be expressed in terms of smoothly summing responses to air and the two pure odorants. Furthermore, the model successfully predicts M/T cell responses to odor mixtures when respiration dependence is eliminated. Thus, odor mixtures are represented in the bulb through summation of components, rather than distinct attractor states. We suggest that our olfactory coding model captures many aspects of single and mixed odor representation in M/T cells.     

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.     

Pharmacological analysis of ionotropic glutamate receptor function in neuronal circuits of the zebrafish olfactory bulb

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca(2+) imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb.     

Connectivity and dynamics in the olfactory bulb

Dendrodendritic interactions between excitatory mitral cells and inhibitory granule cells in the olfactory bulb create a dense interaction network, reorganizing sensory representations of odors and, consequently, perception. Large-scale computational models are needed for revealing how the collective behavior of this network emerges from its global architecture. We propose an approach where we summarize anatomical information through dendritic geometry and density distributions which we use to calculate the connection probability between mitral and granule cells, while capturing activity patterns of each cell type in the neural dynamical systems theory of Izhikevich. In this way, we generate an efficient, anatomically and physiologically realistic large-scale model of the olfactory bulb network. Our model reproduces known connectivity between sister vs. non-sister mitral cells; measured patterns of lateral inhibition; and theta, beta, and gamma oscillations. The model in turn predicts testable relationships between network structure and several functional properties, including lateral inhibition, odor pattern decorrelation, and LFP oscillation frequency. We use the model to explore the influence of cortex on the olfactory bulb, demonstrating possible mechanisms by which cortical feedback to mitral cells or granule cells can influence bulbar activity, as well as how neurogenesis can improve bulbar decorrelation without requiring cell death. Our methodology provides a tractable tool for other researchers.     

Function of attention in learning process in the olfactory bulb

It has been suggested that in the olfactory bulb, odor information is processed through parallel channels and learning depends on the cognitive environment. The synapse’s spike effective time is defined as the effective time for a spike from pre-synapse to post-synapse, which varies with the type of synapse. A learning model of the olfactory bulb was constructed for synapses with varying spike effective times. The simulation results showed that such a model can realize the multi-channel processing of information in the bulb. Furthermore, the effect of the cognitive environment on the learning process was also studied. Different feedback frequencies were used to express different attention states. Considering the information’s multi-channel processing requirement for learning, a learning rule considering both spike timing and average spike frequency is proposed. Simulation results showed that habituation and anti-habituation of an odor in the olfactory bulb might be the result of learning guided by a common local learning rule but at different attention states.     

A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.     

Strong single-fiber sensory inputs to olfactory cortex: implications for olfactory coding

Olfactory information is first encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of odors. This information is then transmitted to piriform (olfactory) cortex, via axons of olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form the odor percept. However, mechanisms governing the integration of sensory information in mammalian olfactory cortex are unclear. Here we show that single M/T cells can make powerful connections with cortical pyramidal cells, and coincident input from few M/T cells is sufficient to elicit spike output. These findings suggest that odor coding is broad and distributed in olfactory cortex.     

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.     

Nonlinear dynamics of paleocortex manifested in the olfactory EEG

The olfactory bulb is the first central component in a highly sensitive yet markedly stable sensory system. It receives a surge of receptor activity with each inspiration and transmits output as a brief burst of oscillatory activity that is most clearly seen in the EEG. These properties together with the known anatomy and physiology of the bulb are used as design criteria to synthesize, evaluate and solve a set of nonlinear differential equations that represent lumped bulbar dynamics. According to the model bulbar processing is in two stages. In the outer layers the interneurons perform the operations of input range compression, integration, clipping, holding, and bias control. In the inner layers the input surge is converted to a burst, which is transmitted by the mitral cells as a pulse density wave. The phase, frequency duration and amplitude of the wave convey information centrally about both the input and the state of the system. The model suffices to replicate the forms of the EEG burst; the pulse probability distributions conditional on the EEG; the waveforms of averaged evoked potentials (AEPs) and post stimulus time (PST) histograms from the bulb and cortex; and the changes in waveform induced by behavioral control of attentiveness and habituation. It is inferred that with selective attention there is a permanent change in the strength of mutually excitatory connections among excitatory neurons, and that with habituation there is a reversible change in the effectiveness of excitatory synapses. The limitations and deficiencies of the model and the need for centrifugal controls of bulbocortical function are discussed.     

Function of attention in learning process in the olfactory bulb

Biological experiments[1—8] have shown that in the olfactory bulb, odor information is encoded into spatio-temporal patterns and processed in multi-channels. In the bulb, the information is divided into basic information and fine information, which are encoded into average spiking frequency (long-term pattern) and synchronization of spikes[1—8] respectively. Compared with other structures in which information is encoded into spatio-temporal patterns, the olfactory bulb抯 structure is rather …     

Understanding Odor Information Segregation in the Olfactory Bulb by Means of Mitral and Tufted Cells

Odor identification is one of the main tasks of the olfactory system. It is performed almost independently from the concentration of the odor providing a robust recognition. This capacity to ignore concentration information does not preclude the olfactory system from estimating concentration itself. Significant experimental evidence has indicated that the olfactory system is able to infer simultaneously odor identity and intensity. However, it is still unclear at what level or levels of the olfactory pathway this segregation of information occurs. In this work, we study whether this odor information segregation is performed at the input stage of the olfactory bulb: the glomerular layer. To this end, we built a detailed neural model of the glomerular layer based on its known anatomical connections and conducted two simulated odor experiments. In the first experiment, the model was exposed to an odor stimulus dataset composed of six different odorants, each one dosed at six different concentrations. In the second experiment, we conducted an odor morphing experiment where a sequence of binary mixtures going from one odor to another through intermediate mixtures was presented to the model. The results of the experiments were visualized using principal components analysis and analyzed with hierarchical clustering to unveil the structure of the high-dimensional output space. Additionally, Fisher''s discriminant ratio and Pearson''s correlation coefficient were used to quantify odor identity and odor concentration information respectively. Our results showed that the architecture of the glomerular layer was able to mediate the segregation of odor information obtaining output spiking sequences of the principal neurons, namely the mitral and external tufted cells, strongly correlated with odor identity and concentration, respectively. An important conclusion is also that the morphological difference between the principal neurons is not key to achieve odor information segregation.     

The olfactory glomerulus: A cortical module with specific functions

The axons of many olfactory receptor cells converge on an individual glomerulus in the olfactory bulb, where they make contacts with the distal dendrites of mitral and tufted cells. Each glomerulus is targeted by olfactory receptor neurons expressing a single type of olfactory receptor protein. The glomerulus provides a unique model in which the function of a cortical module can be unambiguously established. Here we review the increasing evidence that a key functional operation of the glomerulus is to act as a signal-to-noise enhancing device in the processing of sensory input and that this function is critical across vertebrate and invertebrate species for the ability to detect specific odor stimuli within “noisy” odor environments and to carry out discriminations between odor molecules that are structurally closely related.     

The Neuroanatomical Organization of Projection Neurons Associated with Different Olfactory Bulb Pathways in the Sea Lamprey,Petromyzon marinus

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate.     

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.     

Blanes cells mediate persistent feedforward inhibition onto granule cells in the olfactory bulb

Inhibitory local circuits in the olfactory bulb play a critical role in determining the firing patterns of output neurons. However, little is known about the circuitry in the major plexiform layers of the olfactory bulb that regulate this output. Here we report the first electrophysiological recordings from Blanes cells, large stellate-shaped interneurons located in the granule cell layer. We find that Blanes cells are GABAergic and generate large I(CAN)-mediated afterdepolarizations following bursts of action potentials. Using paired two-photon guided intracellular recordings, we show that Blanes cells have a presumptive axon and monosynaptically inhibit granule cells. Sensory axon stimulation evokes barrages of EPSPs in Blanes cells that trigger long epochs of persistent spiking; this firing mode was reset by hyperpolarizing membrane potential steps. Persistent firing in Blanes cells may represent a novel mechanism for encoding short-term olfactory information through modulation of tonic inhibitory synaptic input onto bulbar neurons.     

Reshaping of bulbar odor response by nasal flow rate in the rat

Background

The impact of respiratory dynamics on odor response has been poorly studied at the olfactory bulb level. However, it has been shown that sniffing in the behaving rodent is highly dynamic and varies both in frequency and flow rate. Bulbar odor response could vary with these sniffing parameter variations. Consequently, it is necessary to understand how nasal airflow can modify and shape odor response at the olfactory bulb level.

Methodology and Principal Findings

To assess this question, we used a double cannulation and simulated nasal airflow protocol on anesthetized rats to uncouple nasal airflow from animal respiration. Both mitral/tufted cell extracellular unit activity and local field potentials (LFPs) were recorded. We found that airflow changes in the normal range were sufficient to substantially reorganize the response of the olfactory bulb. In particular, cellular odor-evoked activities, LFP oscillations and spike phase-locking to LFPs were strongly modified by nasal flow rate.

Conclusion

Our results indicate the importance of reconsidering the notion of odor coding as odor response at the bulbar level is ceaselessly modified by respiratory dynamics.     

A biophysical model of vertebrate olfactory epithelium and bulb exhibiting gap junction dependent odor-evoked spatiotemporal patterns of activity

This work describes a biophysical model of the initial stages of vertebrate olfactory system containing structures representing the olfactory epithelium and bulb. Its main novelty is the introduction of gap junctions connecting neurons both in the epithelium and bulb, and of biologically detailed dendrodendritic synapses between granule and mitral cells in the bulb. The model was used to simulate the effect of an odor presentation on the neural activity pattern in the epithelium and bulb. During the time for which an odor is presented with a constant concentration, there are spatiotemporal patterns in the epithelium and bulb generated by the couplings due to the gap junctions and/or dendrodendritic synapses. A study varying the strength of the gap junction coupling shows that the spatiotemporal patterns, both in the epithelium and bulb, are dependent of the coupling strength. It is also shown that the olfactory bulb's spatiotemporal pattern depends on the existence of the dendrodendritic connections between mitral and granule cells. If these spatiotemporal patterns really exist in the early processing stages of the olfactory system they may be used for odor coding and the gap junctions and dendrodendritic synapses might have a role on it.     

Regulation of c-Fos expression in the rat olfactory bulbs during olfactory learning

The distribution of c-Fos-immunopositive neurons was examined in the mitral/tufted and granular cell layers in the medium part of the main olfactory bulbs of 18-day-old rats after they had been trained for propionic acid vapour-guided search for dam in the Y-maze. On the next day these pups exhibited a strong preference for the propionic acid odor as compared to the control pups trained for this task without the odor cue and odor-familiarized pups exposed to propionic acid as a novel neutral stimulus. Exposure to propionic acid produced a moderate activation of c-Fos expression, mainly in the granular layer of the dorsomedial part of the bulb. Training in the Y-maze devoid of odor cues resulted in diffuse increase in the number of c-Fos-positive neurons both in the mitral and granular cell layers in all parts of the olfactory bulb. Maze training with the odor cue produced activation of c-Fos expression (which significantly exceeded the non-odor Y-maze group) in the dorsomedial olfactory bulb. These data suggest that associative olfactory conditioning results in activation of c-Fos expression that combines the effect of diffuse motivational excitation and specific olfactory input to the neurons which process odor cues.     

Electrophysiological responses of olfactory bulb neurons to odour stimuli in the frog. A comparison with receptor cells

Extracellular recordings were performed from olfactory bulbneurons in the frog. The odour stimuli were the same as thosepreviously used for studying the receptor cells in the sameanimal species and were delivered at similar concentrations(Revial et al., 1982). The general properties of the neuronresponses are presented and discussed with reference to homologousproperties of olfactory receptor cells. The response rates elicitedby different stimuli from the bulbar neurons were found to behighly correlated with those elicited from receptor cells. Theindividual cell selectivity was better in the bulb than in theolfactory epithelium. The olfactory bulb neurons seemed to improvethe discrimination between stimuli (enantiomers) poorly distinguishedby the receptor cells. Reducing odor concentration caused therate of suppressive response to decrease faster than that ofexcitatory ones, suggesting that the manifestations of inhibitoryprocesses in some neurons requires a high level of excitationin others.     

Response accuracy and odor sampling time in mice trained to discriminate between enantiomers of carvone and those of terpinen-4-ol

Response accuracy and odor-sampling times were used to compare the ability of mice to detect (+)-carvone and (+)-terpinen-4-ol and to discriminate between enantiomers of carvone and of terpinen-4-ol. Except for increased odor sampling when mice were first exposed to the (+)-carvone odor, there was no difference in odor-sampling time or response accuracy in tests of odor detection or in discriminating between enantiomers of these odorants. These results fail to support the suggestion that odorants that produce different patterns of olfactory bulb activation should be easier to discriminate than those that produce much more similar patterns of bulbar activation.