Mouse Main Olfactory Bulb Research Articles

Uncover spatially informed variations for single-cell spatial transcriptomics with STew.

The recent spatial transcriptomics (ST) technologies have enabled characterization of gene expression patterns and spatial information, advancing our understanding of cell lineages within diseased tissues. Several analytical approaches have been proposed for ST data, but effectively utilizing spatial information to unveil the shared variation with gene expression remains a challenge. We introduce STew, a Spatial Transcriptomic multi-viEW representation learning method, to jointly analyze spatial information and gene expression in a scalable manner, followed by a data-driven statistical framework to measure the goodness of model fit. Through benchmarking using human dorsolateral prefrontal cortex and mouse main olfactory bulb data with true manual annotations, STew achieved superior performance in both clustering accuracy and continuity of identified spatial domains compared with other methods. STew is also robust to generate consistent results insensitive to model parameters, including sparsity constraints. We next applied STew to various ST data acquired from 10× Visium, Slide-seqV2, and 10× Xenium, encompassing single-cell and multi-cellular resolution ST technologies, which revealed spatially informed cell type clusters and biologically meaningful axes. In particular, we identified a proinflammatory fibroblast spatial niche using ST data from psoriatic skins. Moreover, STew scales almost linearly with the number of spatial locations, guaranteeing its applicability to datasets with thousands of spatial locations to capture disease-relevant niches in complex tissues. Source code and the R software tool STew are available from github.com/fanzhanglab/STew.

Cannabinoid Receptor‐Mediated Synaptic Signaling and Neural Plasticity in Central Olfactory Neurons

Our studies aim to understand integrative and computational mechanisms that allow main olfactory bulb neurons to respond to afferent input and synaptic or feedback signals. The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions but our understanding of the role of cannabinoid receptor type 1 (CB1R) in olfactory processing remains limited. Endocannabinoids are known to mediate retrograde signaling at synapses in several brain regions through a form of short‐term neural plasticity. Endocannabinoids are released from depolarized principal neurons and rapidly diffuse to presynaptic inhibitory interneurons to transiently reduce presynaptic firing and neurotransmitter (GABA) release (Depolarization‐Induced Suppression of Inhibition, DSI).We study the function of the endocannabinoid system in regulating neural activity at synapses in the main olfactory bulb, the first central relay station in the brain for the processing of olfactory information coming from the nose. Our experimental approach uses electrophysiological recording techniques, specifically whole cell patch‐clamp recordings. Previously, using anatomical approaches, we showed that CB1R is present in periglomerular processes of a GAD65‐positive population of interneurons but not in mitral cells, key output neurons. We detected eCBs in the mouse main olfactory bulb as well as the expression of CB1R and other genes associated with the cannabinoid signaling system.Output neurons such as mitral cells and tufted cells in the olfactory bulb are computational elements in brain circuits that integrate incoming signals with membrane properties to generate behaviorally relevant synaptic output. Our data support the notion that retrograde signaling is present in neural circuits involving mitral and tufted cells. Mitral and tufted cells release endocannabinoids and, through retrograde signaling, inhibit presynaptic interneurons such as periglomerular cells, which controls the GABA release of these presynaptic neurons. This, in turn, allows mitral and tufted cells to temporarily regulate their synaptic input and relieve them from synaptic inhibition. Endocannabinoids function as retrograde messengers to regulate neural signaling and mediate plasticity at olfactory bulb synapses with potential effects on olfactory threshold and behavior.

Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb.

The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions. Our understanding of the role of cannabinoid receptor type 1 (CB1) in olfactory processing remains limited. Cannabinoid signaling is involved in regulating glomerular activity in the main olfactory bulb (MOB). However, the cannabinoid-related circuitry of inputs to mitral cells in the MOB has not been fully determined. Using anatomical and functional approaches we have explored this question. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons but not in mitral cells. We detected eCBs in the mouse MOB as well as the expression of CB1 and other genes associated with cannabinoid signaling in the MOB. Patch-clamp electrophysiology demonstrated that CB1 agonists activated mitral cells and evoked an inward current, while CB1 antagonists reduced firing and evoked an outward current. CB1 effects on mitral cells were absent in subglomerular slices in which the olfactory nerve layer and glomerular layer were removed, suggesting the glomerular layer as the site of CB1 action. We previously observed that GABAergic periglomerular cells show the inverse response pattern to CB1 activation compared with mitral cells, suggesting that CB1 indirectly regulates mitral cell activity as a result of cellular activation of glomerular GABAergic processes . This hypothesis was supported by the finding that cannabinoids modulated synaptic transmission to mitral cells. We conclude that CB1 directly regulates GABAergic processes in the glomerular layer to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.NEW & NOTEWORTHY Cannabinoid signaling with cannabinoid receptor type 1 (CB1) is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). We detected endocannabinoids in the mouse MOB. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons. CB1 agonists activated mitral cells. CB1 directly regulates GABAergic processes to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.

Narrowly Confined and Glomerulus-Specific Onset Latencies of Odor-Evoked Calcium Transients in the Juxtaglomerular Cells of the Mouse Main Olfactory Bulb.

Odor information is transmitted from olfactory sensory neurons to principal neurons at the glomeruli of the olfactory bulb. The intraglomerular neuronal circuit also includes hundreds of interneurons referred to as juxtaglomerular (JG) cells. Stimulus selectivity is well correlated among many JG cells that are associated with the same glomerulus, consistent with their highly homogeneous sensory inputs. However, much less is known about the temporal aspects of their activity, including the temporal coordination of their odor-evoked responses. As many JG cells within a glomerular module respond to the same stimulus, the extent to which their activity is temporally aligned will affect the temporal profile of their population inhibitory inputs. Using random-access high-speed two-photon microscopy, we recorded the odor-evoked calcium transients of mouse JG cells and compared the onset latency and rise time among neurons putatively associated with the same and different glomeruli. Whereas the overall onset latencies of odor-evoked transients were distributed across a ∼150 ms time window, those from cells putatively associated with the same glomerulus were confined to a much narrower window of several tens of milliseconds. This result suggests that onset latency primarily depends on the associated glomerulus. We also observed glomerular specificity in the rise time. The glomerulus-specific temporal pattern of odor-evoked activity implies that the temporal patterns of inputs from the intraglomerular circuit are unique to individual glomerulus–odor pairs, which may contribute to efficient shaping of the temporal pattern of activity in the principal neurons.

Activation of Group II Metabotropic Glutamate Receptors Suppresses Excitability of Mouse Main Olfactory Bulb External Tufted and Mitral Cells.

Metabotropic glutamate receptors (mGluRs) are abundantly expressed in the rodent main olfactory bulb. The function of Group I mGluRs has been investigated in a number of studies, while the actions of Group II mGluRs, which include the mGluR2 and mGluR3 subtypes, have been less well explored. Here, we used electrophysiological approaches in mouse olfactory bulb slices to investigate how Group II mGluR activation and inactivation modifies the activity of external tufted (ET) and mitral cells. The Group II mGluR agonist DCG-IV was found to directly and uniformly reduce the spontaneous discharge of ET and mitral cells. The inhibitory effect of DCG-IV was absent in mitral cells with truncated apical dendrites, indicating a glomerular site of action. DCG-IV did not influence olfactory nerve-evoked monosynaptic responses in ET or mitral cells, indicating that Group II mGluRs do not presynaptically modulate glutamate release from olfactory nerve terminals. In contrast, DCG-IV suppressed polysynaptic responses in periglomerular cells evoked by olfactory nerve stimulation. DCG-IV also inhibited glutamate release from ET cells, and suppressed the spontaneous and olfactory nerve-evoked long-lasting depolarization in mitral cells. Applied alone, Group II receptor antagonists were without effect, suggesting that basal activation of these receptors is nil. These findings suggest that Group II mGluRs inhibit ET and mitral cell activity and further dampen intraglomerular excitatory circuits by suppressing glutamate release.

Odorant receptor proteins in the mouse main olfactory epithelium and olfactory bulb

In the mouse, odorant receptor proteins (ORs) are G-protein-coupled receptors expressed in mature olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE). ORs mediate odorant reception at the level of the OSN cilia. Most of the ∼1100 OR genes in the mouse genome are expressed, at the RNA level, in mature OSNs. The literature on antibodies against ORs is limited, and most reports are with antibodies that are not commercially available. Here we have screened 40 commercial antibodies against human and mouse ORs by immunofluorescence staining of coronal cryosections of the MOE of 21-day-old C57BL/6J mice. Various methods of antigen retrieval were tested. Of the 19 antibodies raised against human ORs, three yielded a consistent immunoreactive signal in the mouse MOE; of these three, two appeared to cross react against one or more, unknown, mouse ORs. Of the 21 antibodies raised against mouse ORs, six yielded a consistent immunoreactive signal in the mouse MOE; of these six, two also stained specific glomeruli in the olfactory bulb. Antibody specificity could be validated with gene-targeted mouse strains in the case of three ORs. The number of OSNs immunoreactive for the MOR28/Olfr1507 antibody is greater in C57BL/6J than in 129S6/SvEvTac wild-type mice. Taken together, our results are encouraging: 20–30% of these commercially available antibodies are informative in immunohistochemical analyses of the mouse MOE. The commercial availability of these antibodies should facilitate the study of OR proteins in the MOE and the olfactory bulb, and the replicability of results in the literature.

Activation of β-noradrenergic receptors enhances rhythmic bursting in mouse olfactory bulb external tufted cells.

The main olfactory bulb (MOB) receives a rich noradrenergic innervation from the nucleus locus coeruleus. Despite the well-documented role of norepinephrine and β-adrenergic receptors in neonatal odor preference learning, identified cellular physiological actions of β-receptors in the MOB have remained elusive. β-Receptors are expressed at relatively high levels in the MOB glomeruli, the location of external tufted (ET) cells that exert an excitatory drive on mitral and other cell types. The present study investigated the effects of β-receptor activation on the excitability of ET cells with patch-clamp electrophysiology in mature mouse MOB slices. Isoproterenol and selective β2-, but not β1-, receptor agonists were found to enhance two key intrinsic currents involved in ET burst initiation: persistent sodium (INaP) and hyperpolarization-activated inward (Ih) currents. Together, the positive modulation of these currents increased the frequency and strength of ET cell rhythmic bursting. Rodent sniff frequency and locus coeruleus neuronal firing increase in response to novel stimuli or environments. The increase in ET excitability by β-receptor activation may better enable ET cell rhythmic bursting, and hence glomerular network activity, to pace faster sniff rates during heightened norepinephrine release associated with arousal.

Secretagogin-containing neurons in the mouse main olfactory bulb

Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family. We studied the structural features of SCGN-positive neurons in the mouse main olfactory bulb (MOB). SCGN-positive neurons were localized throughout layers but clustered in the glomerular layer (GL), mitral cell layer (MCL) and granule cell layer (GCL). They were heterogeneous, including numerous juxtaglomerular neurons, granule cells, small to medium-sized neurons in the external plexiform layer (EPL), and a few small cells in the ependymal/subependymal layer. Calretinin and/or tyrosine hydroxylase occasionally colocalized in SCGN-positive juxtaglomerular neurons. Calretinin also frequently colocalized in SCGN-positive EPL and GCL neurons. Morphologically some of juxtaglomerular SCGN-positive neurons were classical periglomerular cells, whereas others were apparently different from those periglomerular cells, although they were further heterogeneous. Some extended one slender process into a glomerulus which passed the glomerulus and further penetrated into another nearby glomeruli, and thus their dendritic processes spanned two or three or more glomeruli. We named this type of juxtaglomerular neurons “transglomerular cells.” With the stereological analysis we estimated total number of juxtaglomerular SCGN-positive neurons at about 80,000/single MOB. The present study revealed the diversity of SCGN-positive neurons in the mouse MOB and their particular structural properties hitherto unknown.

Optogenetic Activation of Basal Forebrain Cholinergic Neurons Modulates Neuronal Excitability and Sensory Responses in the Main Olfactory Bulb

The main olfactory bulb (MOB) in mammals receives massive centrifugal input from cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, the activity of which is thought to be correlated with animal behaving states, such as attention. Cholinergic signals in the bulb facilitate olfactory discrimination and learning, but it has remained controversial how the activity of HDB cholinergic neurons modulates neuronal excitability and olfactory responses in the MOB. In this study, we used an optogenetic approach to selectively activate HDB cholinergic neurons and recorded the effect of this activation on the spontaneous firing activity and odor-evoked responses of mouse MOB neurons. Cells were juxtacellularly labeled and their specific types were morphologically determined. We find that light stimulation of HDB cholinergic neurons inhibits the spontaneous firing activity of all major cell types, including mitral/tufted (M/T) cells, periglomerular (PG) cells, and GABAergic granule cells. Inhibitions are significantly produced by stimulation at 10 Hz and further enhanced at higher frequencies. In addition, cholinergic activation sharpens the olfactory tuning curves of a majority of M/T cells but broadly potentiates odor-evoked responses of PG cells and granule cells. These results demonstrate strong effects of the basal forebrain cholinergic system on modulating neuronal excitability in the MOB and support the hypothesis that cholinergic activity increases olfactory discrimination capability.

Further characterization of the juxtaglomerular neurons in the mouse main olfactory bulb by transcription factors, Sp8 and Tbx21

Juxtaglomerular neurons in the mouse main olfactory bulb consist of various types of neurons, especially classified by their chemical properties such as transmitter-related molecules and calcium binding proteins. In addition several transcription factors have been revealed to characterize neuronal subpopulations. In this study we examined the immunoreactivities of two transcription factors, Sp8 and Tbx21, in the juxtaglomerular neuronal subpopulations containing calretinin, calbindin, secretagogin, tyrosine hydroxylase (TH) and nitric oxide synthase (NOS). Both Sp8 and Tbx21 immunoreactivities were so diverse in their staining intensities. Almost all calretinin and secretagogin positive neurons were relatively strongly Sp8 positive, whereas none of calbindin positive neurons were Sp8 positive. TH positive neurons were also usually Sp8 positive, although some were faintly positive. These four types of interneurons were Tbx21 negative. On the other hand large faintly NOS positive external tufted cells were occasionally Tbx21 positive but always Sp8 negative, whereas small NOS positive periglomerular cells without distinctly stained dendrites were usually Sp8 positive and Tbx21 negative. Strangely, most of strongly NOS positive periglomerular cells with distinctly stained dendritic processes were Sp8 negative and Tbx21 negative. Thus Sp8 and Tbx21 immunoreactivities further characterized juxtaglomerular neurons and, especially confirmed the heterogeneity of NOS positive juxtaglomerular neurons.

Comprehensive connectivity of the mouse main olfactory bulb: analysis and online digital atlas

We introduce the first open resource for mouse olfactory connectivity data produced as part of the Mouse Connectome Project (MCP) at UCLA. The MCP aims to assemble a whole-brain connectivity atlas for the C57Bl/6J mouse using a double coinjection tracing method. Each coinjection consists of one anterograde and one retrograde tracer, which affords the advantage of simultaneously identifying efferent and afferent pathways and directly identifying reciprocal connectivity of injection sites. The systematic application of double coinjections potentially reveals interaction stations between injections and allows for the study of connectivity at the network level. To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org). Systematic double coinjections were made into different regions of the main olfactory bulb (MOB) and data from 18 MOB cases (~72 pathways; 36 efferent/36 afferent) currently are available to view in iConnectome within their corresponding atlas level and their own bright-field cytoarchitectural background. Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available. Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections.

Distinct odor representation of individual neurons within a single glomerulus module in the mouse main olfactory bulb

Distinct odor representation of individual neurons within a single glomerulus module in the mouse main olfactory bulb

Visualization of nitric oxide production in the mouse main olfactory bulb by a cell-trappable copper(II) fluorescent probe

We report the visualization of NO production using fluorescence in tissue slices of the mouse main olfactory bulb. This discovery was possible through the use of a novel, cell-trappable probe for intracellular nitric oxide detection based on a symmetric scaffold with two NO-reactive sites. Ester moieties installed onto the fluorescent probe are cleaved by intracellular esterases to yield the corresponding negatively charged, cell-impermeable acids. The trappable probe Cu(2)(FL2E) and the membrane-impermeable acid derivative Cu(2)(FL2A) respond rapidly and selectively to NO in buffers that simulate biological conditions, and application of Cu(2)(FL2E) leads to detection of endogenously produced NO in cell cultures and olfactory bulb brain slices.

Heterogeneity of calbindin-containing neurons in the mouse main olfactory bulb: I. General description

The structural features of calbindin-positive neurons were studied in the mouse main olfactory bulb (MOB). Calbindin-positive neurons were heterogeneous, including numerous periglomerular cells, a few granule cells, small to medium-sized interneurons in the external plexiform layer, and large short-axon cells located in the external plexiform layer, internal plexiform layer, granule cell layer and ependymal/subependymal layer. These large short-axon cells were also heterogeneous; some corresponded to classically identified short-axon cells such as Blanes cells, Golgi cells, horizontal cells and vertical cells, but some others appeared to be previously unidentified. A few faintly calbindin-positive presumed tufted cells were also encountered. Near the ependymal/subependymal layer of the MOB some calbindin-positive short-axon cells extended their dendritic processes more or less parallel to the sagittal plane, presumably corresponding to medullary cells named recently. In addition we encountered a few calbindin-positive horizontal cells in the internal plexiform layer extending their axons toward the lateral olfactory tract, one of which was confirmed to extend its axon into the lateral olfactory tract, indicating that they were presumed to be one of projection neurons. The present study revealed the diversity of calbindin-positive neurons in the mouse MOB and their particular structural properties hitherto unknown.

Somatostatin interneurons delineate the inner part of the external plexiform layer in the mouse main olfactory bulb

Neuropeptides play a major role in the modulation of information processing in neural networks. Somatostatin, one of the most concentrated neuropeptides in the brain, is found in many sensory systems including the olfactory pathway. However, its cellular distribution in the mouse main olfactory bulb (MOB) is yet to be characterized. Here we show that approximately 95% of mouse bulbar somatostatin-immunoreactive (SRIF-ir) cells describe a homogeneous population of interneurons. These are restricted to the inner lamina of the external plexiform layer (iEPL) with dendritic field strictly confined to the region. iEPL SRIF-ir neurons share some morphological features of Van Gehuchten short-axon cells, and always express glutamic acid decarboxylase, calretinin, and vasoactive intestinal peptide. One-half of SRIF-ir neurons are parvalbumin-ir, revealing an atypical neurochemical profile when compared to SRIF-ir interneurons of other forebrain regions such as cortex or hippocampus. Somatostatin is also present in fibers and in a few sparse presumptive deep short-axon cells in the granule cell layer (GCL), which were previously reported in other mammalian species. The spatial distribution of somatostatin interneurons in the MOB iEPL clearly outlines the region where lateral dendrites of mitral cells interact with GCL inhibitory interneurons through dendrodendritic reciprocal synapses. Symmetrical and asymmetrical synaptic contacts occur between SRIF-ir dendrites and mitral cell dendrites. Such restricted localization of somatostatin interneurons and connectivity in the bulbar synaptic network strongly suggest that the peptide plays a functional role in the modulation of olfactory processing.

Somatostatin Contributes toIn VivoGamma Oscillation Modulation and Odor Discrimination in the Olfactory Bulb

Neuropeptides are systematically encountered in local interneurons, but their functional contribution in neural networks is poorly documented. In the mouse main olfactory bulb (MOB), somatostatin is mainly concentrated in local GABAergic interneurons restricted to the external plexiform layer (EPL). Immunohistochemical experiments revealed that the sst2 receptor, the major somatostatin receptor subtype in the telencephalon, is expressed by mitral cells, the MOB principal cells. As odor-activated mitral cells synchronize and generate gamma oscillations of the local field potentials, we investigated whether pharmacological manipulations of sst2 receptors could influence these oscillations in freely behaving mice. In wild-type, but not in sst2 knock-out mice, gamma oscillation power decreased lastingly after intrabulbar injection of an sst2-selective antagonist (BIM-23627), while sst2-selective agonists (octreotide and L-779976) durably increased it. Sst2-mediated oscillation changes were correlated with modifications of the dendrodendritic synaptic transmission between mitral and granule cells. Finally, bilateral injections of BIM-23627 and octreotide respectively decreased and increased odor discrimination performances. Together, these results suggest that endogenous somatostatin, presumably released from EPL interneurons, affects gamma oscillations through the dendrodendritic reciprocal synapse and contributes to olfactory processing. This provides the first direct correlation between synaptic, oscillatory, and perceptual effects induced by an intrinsic neuromodulator.

Two types of tyrosine hydroxylase positive GABAergic juxtaglomerular neurons in the mouse main olfactory bulb are different in their time of origin

Tyrosine hydroxylase (TH) positive juxtaglomerular neurons in the olfactory bulb consist of at least two groups with different soma sizes. On the other hand TH positive neurons are known to be generated continuously in the postnatal and even adult periods. We investigated the birth dates of small- and large-sized TH positive juxtaglomerular neurons. 5-Bromo-2′-deoxyuridine (BrdU) was injected at various developmental and juvenile stages and BrdU-labeled neurons were examined in adult mice. We revealed that both small- and large-sized TH positive neurons were generated at embryonic and perinatal periods and that TH positive neurons generated at the juvenile period were small-sized but not large-sized juxtaglomerular cells.

Sodium channel cluster, βIV-spectrin and ankyrinG positive “hot spots” on dendritic segments of parvalbumin-containing neurons and some other neurons in the mouse and rat main olfactory bulbs

Axon initial segments (AISs) and nodes of Ranvier are considered as the sites for spike generation, which are highly enriched in sodium channels and some cytoskeletal molecules such as ankyrinG, βIV-spectrin. Previously, we showed that most parvalbumin positive cells in the external plexiform layer (EPL) of the mouse main olfactory bulb (MOB) were anaxonic but displayed some patch-like βIV-spectrin and sodium channel cluster positive segments on their dendrites. In this study we further characterized those particular dendritic segments. AnkyrinG was also located there, whereas phospho-IκBα was not. Electron-microscopically those dendritic segments displayed the membrane undercoating characteristic to the AISs and nodes of Ranvier, further confirming their resemblance to the spike generation sites, “hot spots”. Three-dimensional analysis revealed that each parvalbumin positive EPL neuron had 2–7 hot spots, 3–28 μm in length and located 7–50 μm from the somata. Similar “hot spots” were also encountered on a few calretinin positive granule cells and nitric oxide synthase positive periglomerular cells in the mouse MOB. In addition parvalbumin positive EPL cells in the rat MOB displayed similar multiple dendritic “hot spots”. Our study suggested that these morphologically identified dendritic “hot spots” might correspond to dendritic spike generation sites of those neurons.

Increased dopamine after mating impairs olfaction and prevents odor interference with pregnancy

In rodents, social odor sensing influences female reproductive status by affecting neuroendocrine cascades. The odor of male mouse urine can induce ovulation or block pregnancy within 3 d post coitus. Females avoid the action of such olfactory stimuli after embryonic implantation. The mechanisms underlying these changes are unknown. Here we report that shortly after mating, a surge in dopamine in the mouse main olfactory bulb impairs the perception of social odors contained in male urine. Treatment of females at 6.5 d post coitus with a dopamine D2 receptor antagonist restores social odor sensing and favors disruption of pregnancy by inhibition of prolactin release, when administered in the presence of alien male urine odors. These results show that an active sensory barrier blocks social olfactory cues detrimental to pregnancy, consistent with the main olfactory bulb being a major relay through which social odor modulates reproductive status.

Precise Circuitry Links Bilaterally Symmetric Olfactory Maps

Olfactory sensory neurons expressing a common receptor gene converge onto one or a few glomeruli with stereotyped positions within the mouse main olfactory bulb (MOB), producing a map of approximately 1800 olfactory columns representing approximately 1000 odorant receptors. Here, we report that this precise olfactory map is maintained over several synapses that ultimately cross MOB hemispheres to link bilateral isofunctional olfactory columns. Focal injection of tracer into genetically identified glomeruli revealed an exquisite topography that involves a bilateral connection via the anterior olfactory nucleus pars externa (AONpE) that links isofunctional olfactory columns in the contralateral MOB. Physiological and behavioral assays revealed an important role for the AONpE in bilateral exchange of odorant-specific information. These results indicate that the interbulbar link through the AONpE integrates bilateral olfactory sensory maps and exchanges olfactory information, positioning it as a unique model system for studying interhemispheric connections.