Odor Information Processing Research Articles

The functional logic of odor information processing in the Drosophila antennal lobe.

Recent advances in molecular transduction of odorants in the Olfactory Sensory Neurons (OSNs) of the Drosophila Antenna have shown that the odorant object identity is multiplicatively coupled with the odorant concentration waveform. The resulting combinatorial neural code is a confounding representation of odorant semantic information (identity) and syntactic information (concentration). To distill the functional logic of odor information processing in the Antennal Lobe (AL) a number of challenges need to be addressed including 1) how is the odorant semantic information decoupled from the syntactic information at the level of the AL, 2) how are these two information streams processed by the diverse AL Local Neurons (LNs) and 3) what is the end-to-end functional logic of the AL? By analyzing single-channel physiology recordings at the output of the AL, we found that the Projection Neuron responses can be decomposed into a concentration-invariant component, and two transient components boosting the positive/negative concentration contrast that indicate onset/offset timing information of the odorant object. We hypothesized that the concentration-invariant component, in the multi-channel context, is the recovered odorant identity vector presented between onset/offset timing events. We developed a model of LN pathways in the Antennal Lobe termed the differential Divisive Normalization Processors (DNPs), which robustly extract the semantics (the identity of the odorant object) and the ON/OFF semantic timing events indicating the presence/absence of an odorant object. For real-time processing with spiking PN models, we showed that the phase-space of the biological spike generator of the PN offers an intuit perspective for the representation of recovered odorant semantics and examined the dynamics induced by the odorant semantic timing events. Finally, we provided theoretical and computational evidence for the functional logic of the AL as a robust ON-OFF odorant object identity recovery processor across odorant identities, concentration amplitudes and waveform profiles.

Effects of estradiol on dopaminergic synapse formation in the mouse olfactory bulb.

Olfactory glomeruli are the sites of initial synaptic integration in olfactory information processing. They are surrounded by juxtaglomerular (JG) cells, which include periglomerular, superficial short axon, and external tufted cells. A subpopulation of JG cells expresses the dopamine synthetic enzymes, tyrosine hydroxylase (TH), and aromatic l-amino acid decarboxylase (AADC). TH cells corelease γ-aminobutyric acid (GABA) and their processes extend to multiple glomeruli forming intra- and interglomerular circuits. It is well established that 17β-estradiol (E2) exerts wide ranging effects in the central nervous system. However, participation of E2 in the modulation of neurotransmission and synaptic plasticity of TH cells in olfactory glomeruli is unknown. To address this, we subcutaneously implanted a 60-day release pellet of E2 or placebo into intact male mice and compared glomerular TH, AADC, and vesicular γ-aminobutyric acid transporter (VGAT) immunoreactivity between them. High-voltage electron microscopy (HVEM) and ultra-HVEM using immunogold revealed significantly increased immunoreactive intensity at the cellular level for TH and AADC after E2 treatment and for VGAT in TH cells. These results indicate that E2 may affect the interplay between dopaminergic and GABAergic systems. Moreover, random-section electron microscopy analysis showed a significant increase in the number of symmetrical synapses from TH cell to mitral/tufted cell dendrites after E2 treatment. This result was supported by quantitative immunofluorescence staining with synapse markers. Together, these data indicate that E2 may regulate inhibition between TH cells and olfactory bulb neurons within the glomerulus via interaction between dopaminergic and GABAergic systems, thereby contributing to neuromodulation of odor information processing.

Hierarchical Elemental Odor Coding for Fine Discrimination Between Enantiomer Odors or Cancer-Characteristic Odors.

Odors trigger various emotional responses such as fear of predator odors, aversion to disease or cancer odors, attraction to male/female odors, and appetitive behavior to delicious food odors. Odor information processing for fine odor discrimination, however, has remained difficult to address. The olfaction and color vision share common features that G protein-coupled receptors are the remote sensors. As different orange colors can be discriminated by distinct intensity ratios of elemental colors, such as yellow and red, odors are likely perceived as multiple elemental odors hierarchically that the intensities of elemental odors are in order of dominance. For example, in a mixture of rose and fox-unique predator odors, robust rose odor alleviates the fear of mice to predator odors. Moreover, although occult blood odor is stronger than bladder cancer-characteristic odor in urine samples, sniffer mice can discriminate bladder cancer odor in occult blood-positive urine samples. In forced-choice odor discrimination tasks for pairs of enantiomers or pairs of body odors vs. cancer-induced body odor disorders, sniffer mice discriminated against learned olfactory cues in a wide range of concentrations, where correct choice rates decreased in the Fechner's law, as perceptual ambiguity increased. In this mini-review, we summarize the current knowledge of how the olfactory system encodes and hierarchically decodes multiple elemental odors to control odor-driven behaviors.

Processing of Odor Information During the Respiratory Cycle in Mice.

In the mouse olfactory system, odor signals detected in the olfactory epithelium are converted to a topographic map of activated glomeruli in the olfactory bulb. The map information is then conveyed by projection neurons, mitral cells and tufted cells, to various areas in the olfactory cortex. An odor map is transmitted to the anterior olfactory nucleus by tufted cells for odor identification and recollection of associated memory for learned decisions. For instinct decisions, odor information is directly transmitted to the valence regions in the amygdala by specific subsets of mitral cells. Transmission of orthonasal odor signals through these two distinct pathways, innate and learned, are closely related with exhalation and inhalation, respectively. Furthermore, the retronasal/interoceptive and orthonasal/exteroceptive signals are differentially processed during the respiratory cycle, suggesting that these signals are processed in separate areas of the olfactory bulb and olfactory cortex. In this review article, the recent progress is summarized for our understanding of the olfactory circuitry and processing of odor signals during respiration.

Targeting Insect Olfaction in vivo and in vitro Using Functional Imaging.

Insects decode volatile chemical signals from its surrounding environment with the help of its olfactory system, in a fast and reliable manner for its survival. In order to accomplish this task, odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the fly’s antenna process such odor information. In order to study such a sophisticated process, we require access to the sensory neurons to perform functional imaging. In this article, we present different preparations to monitor odor information processing in Drosophila melanogaster OSNs using functional imaging of their Ca2+ dynamics. First, we established an in vivo preparation to image specific OSN population expressing the fluorescent Ca2+ reporter GCaMP3 during OR activation with airborne odors. Next, we developed a method to extract and to embed OSNs in a silica hydrogel with OR activation by dissolved odors. The odor response dynamics under these different conditions was qualitatively similar which indicates that the reduction of complexity did not affect the concentration dependence of odor responses at OSN level.

Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex.

Olfactory information is encoded in lateral entorhinal cortex (LEC) by two classes of layer 2 (L2) principal neurons: fan and pyramidal cells. However, the functional properties of L2 cells and how they contribute to odor coding are unclear. Here, we show in awake mice that L2 cells respond to odors early during single sniffs and that LEC is essential for rapid discrimination of both odor identity and intensity. Population analyses of L2 ensembles reveal that rate coding distinguishes odor identity, but firing rates are only weakly concentration dependent and changes in spike timing can represent odor intensity. L2 principal cells differ in afferent olfactory input and connectivity with inhibitory circuits and the relative timing of pyramidal and fan cell spikes provides a temporal code for odor intensity. Downstream, intensity is encoded purely by spike timing in hippocampal CA1. Together, these results reveal the unique processing of odor information by LEC subcircuits and highlight the importance of temporal coding in higher olfactory areas.

Valence, Arousal, and Gender Effect on Olfactory Cortical Network Connectivity: A Study Using Dynamic Causal Modeling for EEG

The cortical network including the piriform (PC), orbitofrontal (OFC), and entorhinal (EC) cortices allows the complex processing of behavioral, cognitive, and context-related odor information and represents an access gate to the subcortical limbic regions. Among the several factors that influence odor processing, their hedonic content and gender differences play a relevant role. Here, we investigated how these factors influence EEG effective connectivity among the mentioned brain regions during emotional olfactory stimuli. To this aim, we acquired EEG data from twenty-one healthy volunteers, during a passive odor task of odorants with different valence. We used Dynamic Causal Modeling (DCM) for EEG and Parametric Empirical Bayes (PEB) to investigate the modulatory effects of odors’ valence on the connectivity strengths of the PC-EC-OFC network. Moreover, we controlled for the influence of arousal and gender on such modulatory effects. Our results highlighted the relevant role of the forward and backward PC-EC connections in odor’s brain processing. On the one hand, the EC-to-PC connection was inhibited by both pleasant and unpleasant odors, but not by the neutral one. On the other hand, the PC-to-EC forward connection was found to be modulated (posterior probability (Pp)>0.95) by the arousal level associated with an unpleasant odor. Finally, the whole network dynamics showed several significant gender-related differences (Pp>0.95) suggesting a better ability in odor discrimination for the female gender.

Parallel processing by distinct classes of principal neurons in the olfactory cortex.

Understanding how distinct neuron types in a neural circuit process and propagate information is essential for understanding what the circuit does and how it does it. The olfactory (piriform, PCx) cortex contains two main types of principal neurons, semilunar (SL) and superficial pyramidal (PYR) cells. SLs and PYRs have distinct morphologies, local connectivity, biophysical properties, and downstream projection targets. Odor processing in PCx is thought to occur in two sequential stages. First, SLs receive and integrate olfactory bulb input and then PYRs receive, transform, and transmit SL input. To test this model, we recorded from populations of optogenetically identified SLs and PYRs in awake, head-fixed mice. Notably, silencing SLs did not alter PYR odor responses, and SLs and PYRs exhibited differences in odor tuning properties and response discriminability that were consistent with their distinct embeddings within a sensory-associative cortex. Our results therefore suggest that SLs and PYRs form parallel channels for differentially processing odor information in and through PCx.

Low Fos expression in newly generated neurons of the main and accessory olfactory bulb following single maternal separation

The main and accessory olfactory bulbs (MOB and AOB) are unique in that they produce new neurons throughout adulthood. Despite the recent knowledge about the involvement of postnatally generated cells in several aspects of olfaction, the functional role of these neurons is still not sufficiently understood. The function of newly generated olfactory bulb neurons is primarily investigated in relation to activities related to smell. Stress-induced activation of new olfactory neurons has not yet been studied. Thus, our work was aimed to investigate whether a stressful event, such as maternal separation (MS) can induce Fos expression in postnatally-born neurons in the MOB and AOB. Rat pups were exposed to single maternal separation (SMS) for 2 h at the postnatal days: P7, P14, and P21. Quantification of immunohistochemically labeled Fos + cells revealed that exposure to SMS in different age stages during the first postnatal month stimulates activity in cells of individual MOB/AOB layers in an age-dependent manner. In order to find out whether newly generated cells in the MOB/AOB could express Fos protein as a response to SMS, newborn rats were administrated with the marker of proliferation, bromodeoxyuridine (BrdU) at P0, and three weeks later (at P21) colocalization of Fos and BrdU in the neurons of the MOB and AOB was assessed. Quantitative analysis of BrdU/Fos double-labeled cells showed that Fos is expressed only in a small number of postnatally generated cells within the MOB/AOB. Our results indicate that postnatally generated MOB/AOB neurons are less sensitive to stress caused by MS than preexisting ones. LAY SUMMARY Our results showed that single maternal separation (SMS) is a stressful event that in age-dependent manner stimulates cellular activity in the main and accessory olfactory bulb (AOB) – the structures dedicated to odor information processing. The low level of Fos expression in newborn neurons of the main and accessory bulb indicates that postnatally generated cells are less sensitive to neonatal stress than preexisting neurons.

Differential Impacts of Repeated Sampling on Odor Representations by Genetically-Defined Mitral and Tufted Cell Subpopulations in the Mouse Olfactory Bulb.

Sniffing, the active control of breathing beyond passive respiration, is used by mammals to modulate olfactory sampling. Sniffing allows animals to make odor-guided decisions within ∼200 ms, but animals routinely engage in bouts of high-frequency sniffing spanning several seconds; the impact of such repeated odorant sampling on odor representations remains unclear. We investigated this question in the mouse olfactory bulb (OB), where mitral and tufted cells (MTCs) form parallel output streams of odor information processing. To test the impact of repeated odorant sampling on MTC responses, we used two-photon imaging in anesthetized male and female mice to record activation of MTCs while precisely varying inhalation frequency. A combination of genetic targeting and viral expression of GCaMP6 reporters allowed us to access mitral cell (MC) and superficial tufted cell (sTC) subpopulations separately. We found that repeated odorant sampling differentially affected responses in MCs and sTCs, with MCs showing more diversity than sTCs over the same time period. Impacts of repeated sampling among MCs included both increases and decreases in excitation, as well as changes in response polarity. Response patterns across simultaneously-imaged MCs reformatted over time, with representations of different odorants becoming more distinct. Individual MCs responded differentially to changes in inhalation frequency, whereas sTC responses were more uniform over time and across frequency. Our results support the idea that MCs and TCs comprise functionally distinct pathways for odor information processing, and suggest that the reformatting of MC odor representations by high-frequency sniffing may serve to enhance the discrimination of similar odors.SIGNIFICANCE STATEMENT Repeated sampling of odorants during high-frequency respiration (sniffing) is a hallmark of active odorant sampling by mammals; however, the adaptive function of this behavior remains unclear. We found distinct effects of repeated sampling on odor representations carried by the two main output channels from the mouse olfactory bulb (OB), mitral and tufted cells (MTCs). Mitral cells (MCs) showed more diverse changes in response patterns over time as compared with tufted cells (TCs), leading to odorant representations that were more distinct after repeated sampling. These results support the idea that MTCs contribute different aspects to encoding odor information, and they indicate that MCs (but not TCs) may play a primary role in the modulation of olfactory processing by sampling behavior.

Plasticity of Sniffing Pattern and Neural Activity in the Olfactory Bulb of Behaving Mice During Odor Sampling, Anticipation, and Reward.

The olfactory bulb (OB) is the first relay station in the olfactory system. In the OB, mitral/tufted cells (M/Ts), which are the main output neurons, play important roles in the processing and representation of odor information. Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning. Here, we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice. We used an odor discrimination task combined with in vivo electrophysiological recordings in awake, head-fixed mice, and found that, while learning induced plasticity of spikes and beta oscillations during odor sampling, we also found plasticity of spikes, beta oscillation, sniffing pattern, and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward. These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.

Direct Comparison of Odor Responses of Homologous Glomeruli in the Medial and Lateral Maps of the Mouse Olfactory Bulb.

Olfactory sensory neurons (OSNs) expressing same-type odorant receptors typically project to a pair of glomeruli in the medial and lateral sides of the olfactory bulbs (OBs) in rodents. This multiple glomerular representation of homologous inputs is considered to have more important functional roles for odor information processing than the redundant backup system. However, a consensus idea is lacking and this hinders interpretation of the phenomenon. In addition, the shared and unique odorant response properties of the homologous glomeruli remain unclear because the majority of medial glomeruli are hidden in the septal OB, and thus it is difficult to directly compare them. OSNs, which express trace amine-associated odorant receptors (TAARs), were recently identified that project to a pair of glomeruli uniquely located in the dorsal OB. In this study, we measured the odorant-induced calcium responses of homologous pairs of TAAR glomeruli simultaneously in anesthetized mice and directly compared their response patterns. We found that they exhibited similar temporal response patterns and could not find differences in onset latency, rise time, decay time, or response amplitude. However, the medial glomeruli had significantly larger respiration-locked calcium fluctuations than the lateral glomeruli. This trend was observed with/without odorant stimulation in postsynaptic neurons of GABAergic, dopaminergic, and mitral/tufted cells, but not in presynaptic olfactory sensory axon terminals. This indicates that, at least in these TAAR glomeruli, the medial rather than the lateral OB map enhances the respiration-locked rhythm and transfers this information to higher brain centers.

Coding of odors in the anterior olfactory nucleus.

Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known. In the present study, we recorded the electrical activity of AON neurons in anesthetized rats. Most AON cells fired in bursts of 2–10 spikes separated by very short intervals (<20 ms), in a period linked to the respiratory rhythm. Simultaneous recordings from adjacent neurons revealed that the rhythms of adjacent cells, while locked to the same underlying rhythm, showed marked differences in phase. We studied the responses of AON cells to brief high‐frequency stimulation of the lateral olfactory tract, mimicking brief activation of mitral cells by odor. In different cells, such stimuli evoked transient or sustained bursts during stimulation or, more commonly, post‐stimulation bursts after inhibition during stimulation. This suggests that, in AON cells, phase shifts occur as a result of post‐inhibitory rebound firing, following inhibition by mitral cell input, and we discuss how this supports processing of odor information in the olfactory pathway. Cells were tested for their responsiveness to a social odor (the bedding of a strange male) among other simple and complex odors tested. In total, 11 cells responded strongly and repeatedly to bedding odor, and these responses were diverse, including excitation (transient or sustained), inhibition, and activation after odor presentation, indicating that AON neurons respond not only to the type of complex odor but also to temporal features of odor application.

Target specific functions of EPL interneurons in olfactory circuits

Inhibitory interneurons are integral to sensory processing, yet revealing their cell type-specific roles in sensory circuits remains an ongoing focus. To Investigate the mouse olfactory system, we selectively remove GABAergic transmission from a subset of olfactory bulb interneurons, EPL interneurons (EPL-INs), and assay odor responses from their downstream synaptic partners — tufted cells and mitral cells. Using a combination of in vivo electrophysiological and imaging analyses, we find that inactivating this single node of inhibition leads to differential effects in magnitude, reliability, tuning width, and temporal dynamics between the two principal neurons. Furthermore, tufted and not mitral cell responses to odor mixtures become more linearly predictable without EPL-IN inhibition. Our data suggest that olfactory bulb interneurons, through exerting distinct inhibitory functions onto their different synaptic partners, play a significant role in the processing of odor information.

Leptin modulates olfactory discrimination and neural activity in the olfactory bulb.

Leptin is an important peptide hormone that regulates food intake and plays a crucial role in modulating olfactory function. Although a few previous studies have investigated the effect of leptin on odor perception and discrimination in rodents, research on the neural basis underlying the behavioral changes is lacking. Here we study how leptin affects behavioral performance during a go/no-go task and how it modulates neural activity of mitral/tufted cells in the olfactory bulb, which plays an important role in odor information processing and representation. A go/no-go odor discrimination task was used in the behavioral test. For in vivo studies, single unit recordings, local field potential recordings and fiber photometry recordings were used. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Behaviorally, leptin affects performance and reaction time in a difficult odor-discrimination task. Leptin decreases the spontaneous firing of single mitral/tufted cells, decreases the odor-evoked beta and high gamma local field potential response, and has bidirectional effects on the odor-evoked responses of single mitral/tufted cells. Leptin also inhibits the population calcium activity in genetically identified mitral/tufted cells and granule cells. Furthermore, in vitro slice recordings reveal that leptin inhibits mitral cell activity through direct modulation of the voltage-sensitive potassium channel. The behavioral reduction in odor discrimination observed after leptin administration is likely due to decreased neural activity in mitral/tufted cells, caused by modulation of potassium channels in these cells.

Active Sampling State Dynamically Enhances Olfactory Bulb Odor Representation

SummaryThe olfactory bulb (OB) is the first site of synaptic odor information processing, yet a wealth of contextual and learned information has been described in its activity. To investigate the mechanistic basis of contextual modulation, we use whole-cell recordings to measure odor responses across rapid learning episodes in identified mitral/tufted cells (MTCs). Across these learning episodes, diverse response changes occur already during the first sniff cycle. Motivated mice develop active sniffing strategies across learning that robustly correspond to the odor response changes, resulting in enhanced odor representation. Evoking fast sniffing in different behavioral states demonstrates that response changes during active sampling exceed those predicted from feedforward input alone. Finally, response changes are highly correlated in tufted cells, but not mitral cells, indicating there are cell-type-specific effects on odor representation during active sampling. Altogether, we show that active sampling is strongly associated with enhanced OB responsiveness on rapid timescales.

Adenosine A1 Receptor-Mediated Attenuation of Reciprocal Dendro-Dendritic Inhibition in the Mouse Olfactory Bulb.

It is well described that A1 adenosine receptors inhibit synaptic transmission at excitatory synapses in the brain, but the effect of adenosine on reciprocal synapses has not been studied so far. In the olfactory bulb, the majority of synapses are reciprocal dendro-dendritic synapses mediating recurrent inhibition. We studied the effect of A1 receptor activation on recurrent dendro-dendritic inhibition in mitral cells using whole-cell patch-clamp recordings. Adenosine reduced dendro-dendritic inhibition in wild-type, but not in A1 receptor knock-out mice. Both NMDA receptor-mediated and AMPA receptor-mediated dendro-dendritic inhibition were attenuated by adenosine, indicating that reciprocal synapses between mitral cells and granule cells as well as parvalbumin interneurons were targeted by A1 receptors. Adenosine reduced glutamatergic self-excitation and inhibited N-type and P/Q-type calcium currents, but not L-type calcium currents in mitral cells. Attenuated glutamate release, due to A1 receptor-mediated calcium channel inhibition, resulted in impaired dendro-dendritic inhibition. In behavioral tests we tested the ability of wild-type and A1 receptor knock-out mice to find a hidden piece of food. Knock-out mice were significantly faster in locating the food. Our results indicate that A1 adenosine receptors attenuates dendro-dendritic reciprocal inhibition and suggest that they affect odor information processing.

Evaluation of Culturally-Familiar Odorants for a Persian Smell Identification Test.

Processing odor information by the olfactory system depends greatly on the odor concentration. In order to use an odorant in a smell identification test (SIT), the minimum identification concentration (MIC) needs to be determined. This study was conducted in 60 healthy native individuals aged 20 to 60 years, selected from patients' companions in a tertiary hospital. In the first step, 25 odorants were presented to evaluate familiarity among the subjects. Then, the MICs for the eligible odorants were measured using the ascending method of limits. Out of 25 odorants, only one (cacao) was distinguished by less than 70% of the subjects, and was therefore removed from the list. The MICs of the remaining 24 odorants ranged from 6.87±2.74% for menthol to 27.62±18.98% for cantaloupe. There was significant correlation between age and the MIC only for coffee (P=0.02, r=-0.300). There was a significant difference in MIC between men and women only for hazelnut (P=0.03). We present the MICs of 24 culturally-familiar odorants in a sample of the Persian population in a SIT.

CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior

Granule cells (GCs) in the olfactory bulb (OB) play animportant role in odor information processing. Although they have been classified into various neurochemical subtypes, the functional roles of these subtypes remain unknown. We used invivo two-photon Ca2+ imaging combined with cell-type-specific identification of GCs in the mouse OB to examine whether functionally distinct GC subtypes exist in the bulbar network. We showed that half of GCs express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα+) and that these neurons are preferentially activated by olfactory stimulation. The higher activity of CaMKIIα+ neurons is due to the weaker inhibitory input that they receive compared to their CaMKIIα-immunonegative (CaMKIIα-) counterparts. In line with these functional data, immunohistochemical analyses showed that 75%-90% of GCs expressing the immediate early gene cFos are CaMKIIα+ in naive animals and in mice that have been exposed to a novel odor and go/no-go operant conditioning, or that have been subjected to long-term associative memory and spontaneous habituation/dishabituation odor discrimination tasks. On the other hand, a perceptual learning task resulted in increased activation of CaMKIIα- cells. Pharmacogenetic inhibition of CaMKIIα+ GCs revealed that this subtype is involved in habituation/dishabituation and go/no-go odor discrimination, but not in perceptual learning. In contrast, pharmacogenetic inhibition of GCs in a subtype-independent manner affected perceptual learning. Our results indicate that functionally distinct populations of GCs exist in the OB and that they play distinct roles during different odor tasks.

Zinc as a Neuromodulator in the Central Nervous System with a Focus on the Olfactory Bulb.

The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB. In addition, zinc is contained in the synaptic vesicles of some glycinergic and GABAergic neurons. Thus, zinc released from synaptic vesicles is available to modulate synaptic transmission mediated by excitatory (e.g., N-methyl-D aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)) and inhibitory (e.g., gamma-aminobutyric acid (GABA), glycine) amino acid receptors. Furthermore, extracellular zinc can alter the excitability of neurons through effects on a variety of voltage-gated ion channels. Consistent with the notion that zinc acts as a regulator of neuronal activity, we and others have shown zinc modulation (inhibition and/or potentiation) of amino acid receptors and voltage-gated ion channels expressed by OB neurons. This review summarizes the locations and release of vesicular zinc in the central nervous system (CNS), including in the OB. It also summarizes the effects of zinc on various amino acid receptors and ion channels involved in regulating synaptic transmission and neuronal excitability, with a special emphasis on the actions of zinc as a neuromodulator in the OB. An understanding of how neuroactive substances such as zinc modulate receptors and ion channels expressed by OB neurons will increase our understanding of the roles that synaptic circuits in the OB play in odor information processing and transmission.