Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
To gain insight into the function of AOB and MOB during different social interaction and in different vole species,the behaviors and neural activation of the olfactory bulbs in social interactions of mandarin voles Mi...To gain insight into the function of AOB and MOB during different social interaction and in different vole species,the behaviors and neural activation of the olfactory bulbs in social interactions of mandarin voles Microtus mandarinus and reed voles Microtus fortis were compared in the present research.Mandarin voles spent significantly more time attacking and sniffing their opponents and sniffing sawdust than reed voles.During same sex encounters,mandarin voles attacked their opponents for a significantly longer time and sniffed its opponent for shorter time compared with male-female interactions.However,no significant behavioral differences were found during encounters of two individual reed voles,regardless of gender composition of the pair.Using c-Fos as an indicator of neural activation,we observed that neural activation was significantly higher in almost all sub-regions of the main olfactory bulb(MOB)and the accessory olfactory bulb(AOB)of mandarin voles compared with reed voles.Numbers of c-Fos-ir neurons in almost all sub-regions of the AOB and the MOB during male-female interactions were also higher than those in interactions of the same sex.Anterior-posterior ratios of Fos-ir neurons in the AOBM(AOBMR)and the AOBG(AOBGR)in male-female interaction were significantly higher than those in interaction of the same sex.The AOBMR of male mandarin voles and reed voles were larger than those of females in male-female interactions.Behavioral patterns are consistent with cellular activity patterns.Consistent level of neural activation in MOB and AOB suggests important roles of both the main olfactory bulb and the accessory olfactory bulb in social interaction in two species.展开更多
In order to investigate the neuroendocrine mechanism of the mating behavior in the adult male mandarin voles Microtus mandarinus,the radioimmunoassay(RIA)and immunohistochemistry methods were used to investigate the d...In order to investigate the neuroendocrine mechanism of the mating behavior in the adult male mandarin voles Microtus mandarinus,the radioimmunoassay(RIA)and immunohistochemistry methods were used to investigate the differences in plasma testosterone(T)concentrations and distribution of T immunoreactive neurons(T-IRs),androgen receptor immunoreactive neurons(AR-IRs)and Fos protein immunoreactive neurons(Fos-IRs)in the accessory olfactory bulb(AOB)and the main olfactory bulb(MOB)following exposure to clean hard-wood shavings(control group),soiled bedding(exposure group)or contact with an estrous female(mating group).Results showed that plasma T concentration was significantly higher in the mating group than that in the exposure group,and both the mating group and the exposure group displayed significantly higher plasma T concentration than the control group.T-IRs,AR-IRs and Fos-IRs were investigated with the immunohistochemistry method in granule cell(GC)and mitral cell(MC)of the MOB and the AOB in the three groups.There were significantly more T-IRs,AR-IRs and Fos-IRs in MC and GC of the AOB in the mating group than that in the exposure group or the control group.T-IRs,AR-IRs and Fos-IRs did not show significant differences between the exposure group and the control group.Furthermore,obvious differences in MC and GC of the MOB were not found among the three groups.The results confirm that both changes of T and AR in the AOB might be underlying mating behavior in the adult male mandarin voles.展开更多
Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microe...Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microelectrode technique was used to record extracellular spontaneous electrical activities of olfactory bulb in B. gar-garizans. [Result] Along with the development of olfactory bulb, the discharge types increased gradual y. Single spontaneous firing enhanced gradual y and it reached the maximum in the metamorphosis phase. The intensity of consecutive single sponta-neous firing changed slightly at the middle of post-embryonic development, but it was stil higher than in the early phase and the adult phase. Consecutive burst spontaneous firing frequency went down over time. [Conclusion] Along with the de-velopment of olfactory bulb, the neuronal excitability increases step by step and the neuronal electrical activities diversify gradualy.展开更多
The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comp...The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comparatively with the methods of HE-staining and statistics, through which we studied the development course of dogs＇ olfactory bulb and the structural differences which affect the olfaction in both males and females. The results showed that between both male and female juveniles and adult males and females, the difference in thickness of each layer is not significant. But the difference in quantity of mitral cells between adult males and females was significant. Meanwhile, the structure of every layer in juvenile dogs was apparent while the volume and the weight of adult dogs＇ olfactory bulb and each layer＇s width increased significantly. On the other hand, the density of each layer＇s cells decreased apparently. Our results demonstrated that the olfactory bulb developed with age, and the apparent differences in morphology and quantity of mitral cells between males and females may be one of the reasons leading to the sexual variations of olfactory sensitivity.展开更多
The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volum...The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.展开更多
Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unc...Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 （Hesl） and Hess were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the ol- factory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocyste- inemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.展开更多
Microelectrode technique was used to record the spontaneous electrical activities of the neurons in olfactory bulb of the Bufo bufo gargarizans, both in hibernation and after hibemation. This study investigated the el...Microelectrode technique was used to record the spontaneous electrical activities of the neurons in olfactory bulb of the Bufo bufo gargarizans, both in hibernation and after hibemation. This study investigated the electrophysiological characteristics of amphibian olfactory bulb in the period of hibernation and after hibernation and its effects on the start of hibernation and spontaneous awakening. The research showed four forms of spontaneous firings： single spontaneous firing, burst spontaneous firing, irregular spontaneous firing and consecutive single spontaneous firing. The single spontaneous firing includes slow depolarized spontaneous firing and fast depolarized spontaneous firing, and the slow depolarized spontaneous firing occurs only during the hibernation period. In hibernation, the low amplitude and low frequency firing with a longer duration may be relevant to maintaining the tonicity of the central nervous system in toads that are in hibernation, and this kind of firing may also provide an excited basis for their arousal from hibernation. After hibernation, the amplitude and frequency of firing increase, but the firing duration gets shorter. This form of short-term firing, which may be a phenomenon of sensory neurons fast adapting, is one of the neuronal mechanisms for the arousal of hibernating animals.展开更多
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 informa...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.展开更多
Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-der...Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University(approval No. 2017-073) on February 13, 2017.展开更多
In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximatel...In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.展开更多
Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the ...Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear.Our previous study indicated the potential of APPL2(adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system.In the present study,we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells(NSCs) and an in vivo animal model-APPL2 transgenic(Tg) mice.In the in vitro study,we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis.In the in vivo study,APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system,including the corpus callosum,OB,and rostral migratory stream.Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice.Furthermore,we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors.In conclusion,APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.展开更多
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventual...Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventually damages the structure of the olfactory epithelium,leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Method Two investigators independently searched four databases consisting of PubMed,ProQuest,Scopus,and Web of Science for relevant records as of November 11,2020 with no time,space,and language restrictions.Google Scholar was also searched for the related resources within the time limit of 2020.All the found articles were reviewed based on the PRISMA flow diagram.Qualitative studies,case reports,editorials,letters,and other non-original studies were excluded from this systematic analysis.Results Initial search yielded 434 records.After reviewing the titles and abstracts,we selected 74 articles;finally,8 articles were depicted to be investigated and read in full text.The obtained results showed an increase in the width and volume of the olfactory cleft(OC),complete or partial destruction of OC,and complete occlusion of OC in COVID-19 patients.Deformation and degeneration as well as a subtle asymmetry were evident in the OBs.Computed tomography(CT),meganetic resonance imaging(MRI),and positron emission tomography(PET)were used to detect the outcomes of anosmia in these studies.Conclusions The changes in OC are greater than those in OB in patients with COVID-19,mainly due to the inflammatory and immune responses in OC.However,fewer changes in OB are due to neurological or vascular disorders.Topical steroid therapy and topical saline can be helpful.展开更多
Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular hete...Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.展开更多
Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone...Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles. Cells of the subventricular zone divide and migrate via the rostral migratory stream to the olfactory bulb where they differentiate into granule and pefiglomerular cells. With the discovery of large-sca^e neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Although many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. In this review we highlight the main studies investigating factors that regulate neurogenesis in the subventricular zone, neuronal migration to the olfactory bulb, neuronal integration into the existing bulbar network and shortly discuss the functional meaning of this process.展开更多
The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neu...The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neurons in the OB,mitral/tufted cells encode information such as odor identity and concentration.Recently,the neural strategies and mechanisms underlying odor representation and encoding in the OB have been investigated extensively.Here we review the main progress on this topic.We first review the neurons and circuits involved in odor representation,including the different cell types in the OB and the neural circuits within and beyond the OB.We will then discuss how two different coding strategies—spatial coding and temporal coding—work in the rodent OB.Finally,we discuss potential future directions for this research topic.Overall,this review provides a comprehensive description of our current understanding of how odor information is represented and encoded by mitral/tufted cells in the OB.展开更多
Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca^(2+)signals in genetically-identified neuronal populations.Although fiber photometry is widely used in neurosci...Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca^(2+)signals in genetically-identified neuronal populations.Although fiber photometry is widely used in neuroscience research,the relationship between the recorded Ca^(2+)signals and direct electrophysiological measurements of neural activity remains elusive.Here,we simultaneously recorded odor-evoked Ca^(2+)and electrophysiological signals[single-unit spikes and local field potentials(LFPs)]from mitral/tufted cells in the olfactory bulb of awake,head-fixed mice.Odors evoked responses in all types of signal but the response characteristics(e.g.,type of response and time course)differed.The Ca^(2+)signal was correlated most closely with power in theβ-band of the LFP.The Ca^(2+)signal performed slightly better at odor classification than high-γoscillations,worse than single-unit spikes,and similarly toβoscillations.These results provide new information to help researchers select an appropriate method for monitoring neural activity under specific conditions.展开更多
We characterize the hemodynamic response changes near-infrared spectroscopy （NIRS） during the presentation of in the main olfactory bulb （MOB） of anesthetized rats with three different odorants： （i） plain air a...We characterize the hemodynamic response changes near-infrared spectroscopy （NIRS） during the presentation of in the main olfactory bulb （MOB） of anesthetized rats with three different odorants： （i） plain air as a reference （Blank）, （ii） 2-heptanone （HEP）, and （iii） isopropylbenzene （Ib）. Odorants generate different changes in the concentrations of oxy- hemoglobin. Our results suggest that NIRS technology might be useful in discriminating various odorants in a non-invasive manner using animals with a superb olfactory system.展开更多
The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates thr...The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.展开更多
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
基金supported by National Natural Science Foundation of China(No.30670273No.30200026)Ministry of Education Key Project of Peoples Republic of China(20060718)
文摘To gain insight into the function of AOB and MOB during different social interaction and in different vole species,the behaviors and neural activation of the olfactory bulbs in social interactions of mandarin voles Microtus mandarinus and reed voles Microtus fortis were compared in the present research.Mandarin voles spent significantly more time attacking and sniffing their opponents and sniffing sawdust than reed voles.During same sex encounters,mandarin voles attacked their opponents for a significantly longer time and sniffed its opponent for shorter time compared with male-female interactions.However,no significant behavioral differences were found during encounters of two individual reed voles,regardless of gender composition of the pair.Using c-Fos as an indicator of neural activation,we observed that neural activation was significantly higher in almost all sub-regions of the main olfactory bulb(MOB)and the accessory olfactory bulb(AOB)of mandarin voles compared with reed voles.Numbers of c-Fos-ir neurons in almost all sub-regions of the AOB and the MOB during male-female interactions were also higher than those in interactions of the same sex.Anterior-posterior ratios of Fos-ir neurons in the AOBM(AOBMR)and the AOBG(AOBGR)in male-female interaction were significantly higher than those in interaction of the same sex.The AOBMR of male mandarin voles and reed voles were larger than those of females in male-female interactions.Behavioral patterns are consistent with cellular activity patterns.Consistent level of neural activation in MOB and AOB suggests important roles of both the main olfactory bulb and the accessory olfactory bulb in social interaction in two species.
基金funded by theNatural Science Foundation of China(30670273)Natural Science Foundation of ShaanXi(2008C269)+1 种基金Science and Technology Plan Project of Xi'an Burea of Science and Technology(YF07194)Special Science Research Fund for Xi'an University of Arts and Science(KY200520)
文摘In order to investigate the neuroendocrine mechanism of the mating behavior in the adult male mandarin voles Microtus mandarinus,the radioimmunoassay(RIA)and immunohistochemistry methods were used to investigate the differences in plasma testosterone(T)concentrations and distribution of T immunoreactive neurons(T-IRs),androgen receptor immunoreactive neurons(AR-IRs)and Fos protein immunoreactive neurons(Fos-IRs)in the accessory olfactory bulb(AOB)and the main olfactory bulb(MOB)following exposure to clean hard-wood shavings(control group),soiled bedding(exposure group)or contact with an estrous female(mating group).Results showed that plasma T concentration was significantly higher in the mating group than that in the exposure group,and both the mating group and the exposure group displayed significantly higher plasma T concentration than the control group.T-IRs,AR-IRs and Fos-IRs were investigated with the immunohistochemistry method in granule cell(GC)and mitral cell(MC)of the MOB and the AOB in the three groups.There were significantly more T-IRs,AR-IRs and Fos-IRs in MC and GC of the AOB in the mating group than that in the exposure group or the control group.T-IRs,AR-IRs and Fos-IRs did not show significant differences between the exposure group and the control group.Furthermore,obvious differences in MC and GC of the MOB were not found among the three groups.The results confirm that both changes of T and AR in the AOB might be underlying mating behavior in the adult male mandarin voles.
基金Supported by grants from the Liaoning Provincial Department of Education(2011196)the Experimental Center Director Fund of Shenyang Normal University(sy201003)~~
文摘Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microelectrode technique was used to record extracellular spontaneous electrical activities of olfactory bulb in B. gar-garizans. [Result] Along with the development of olfactory bulb, the discharge types increased gradual y. Single spontaneous firing enhanced gradual y and it reached the maximum in the metamorphosis phase. The intensity of consecutive single sponta-neous firing changed slightly at the middle of post-embryonic development, but it was stil higher than in the early phase and the adult phase. Consecutive burst spontaneous firing frequency went down over time. [Conclusion] Along with the de-velopment of olfactory bulb, the neuronal excitability increases step by step and the neuronal electrical activities diversify gradualy.
基金National Natural Science Foundation of China (30370218)Shan-dong Science Fund for Distinguished Young Scholars(2005BS02005)Science Foundation for Excellent Scholars of Ministry of Education of China (NCET-07-0507)
文摘The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comparatively with the methods of HE-staining and statistics, through which we studied the development course of dogs＇ olfactory bulb and the structural differences which affect the olfaction in both males and females. The results showed that between both male and female juveniles and adult males and females, the difference in thickness of each layer is not significant. But the difference in quantity of mitral cells between adult males and females was significant. Meanwhile, the structure of every layer in juvenile dogs was apparent while the volume and the weight of adult dogs＇ olfactory bulb and each layer＇s width increased significantly. On the other hand, the density of each layer＇s cells decreased apparently. Our results demonstrated that the olfactory bulb developed with age, and the apparent differences in morphology and quantity of mitral cells between males and females may be one of the reasons leading to the sexual variations of olfactory sensitivity.
基金supported by the Hunan Provincial Innovation Foundation for Postgraduate in China,No.CX2014B099(to XH)the Science Foundation of Hunan Provincial Education Department of China,No.11C1264(to FJD),13C958(to XH)
文摘The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.
基金supported by the National Natural Science Foundation of China,No.81560084,81560208a grant from the Project of Superior Discipline Groups in Ningxia Medical University of China,No.XY201414
文摘Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 （Hesl） and Hess were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the ol- factory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocyste- inemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.
基金Liaoning Provincial Department of Education-Funded Project, No. 20068040the Experimental Center of Shenyang Normal University Foundation, No. 2008007
文摘Microelectrode technique was used to record the spontaneous electrical activities of the neurons in olfactory bulb of the Bufo bufo gargarizans, both in hibernation and after hibemation. This study investigated the electrophysiological characteristics of amphibian olfactory bulb in the period of hibernation and after hibernation and its effects on the start of hibernation and spontaneous awakening. The research showed four forms of spontaneous firings： single spontaneous firing, burst spontaneous firing, irregular spontaneous firing and consecutive single spontaneous firing. The single spontaneous firing includes slow depolarized spontaneous firing and fast depolarized spontaneous firing, and the slow depolarized spontaneous firing occurs only during the hibernation period. In hibernation, the low amplitude and low frequency firing with a longer duration may be relevant to maintaining the tonicity of the central nervous system in toads that are in hibernation, and this kind of firing may also provide an excited basis for their arousal from hibernation. After hibernation, the amplitude and frequency of firing increase, but the firing duration gets shorter. This form of short-term firing, which may be a phenomenon of sensory neurons fast adapting, is one of the neuronal mechanisms for the arousal of hibernating animals.
基金supported by the National Natural Science Foundation of China (31571082,31872771 and 31700895)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(16KJA180007)the Natural Science Foundation of Jiangsu Province (BK20170260)。
文摘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.
基金supported by Key Research Projects of Ningxia Hui Autonomous Region of China,No.2018BCG01002(to HCX)the Natural Science Foundation of Ningxia Hui Autonomous Region of China,No.NZ17150(to PY)。
文摘Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University(approval No. 2017-073) on February 13, 2017.
文摘In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.
基金supported by Areas of Excellence (AoE/P-705/16)the General Research Fund,Hong Kong SAR (GRF No.777313 M)。
文摘Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear.Our previous study indicated the potential of APPL2(adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system.In the present study,we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells(NSCs) and an in vivo animal model-APPL2 transgenic(Tg) mice.In the in vitro study,we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis.In the in vivo study,APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system,including the corpus callosum,OB,and rostral migratory stream.Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice.Furthermore,we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors.In conclusion,APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.
文摘Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventually damages the structure of the olfactory epithelium,leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Method Two investigators independently searched four databases consisting of PubMed,ProQuest,Scopus,and Web of Science for relevant records as of November 11,2020 with no time,space,and language restrictions.Google Scholar was also searched for the related resources within the time limit of 2020.All the found articles were reviewed based on the PRISMA flow diagram.Qualitative studies,case reports,editorials,letters,and other non-original studies were excluded from this systematic analysis.Results Initial search yielded 434 records.After reviewing the titles and abstracts,we selected 74 articles;finally,8 articles were depicted to be investigated and read in full text.The obtained results showed an increase in the width and volume of the olfactory cleft(OC),complete or partial destruction of OC,and complete occlusion of OC in COVID-19 patients.Deformation and degeneration as well as a subtle asymmetry were evident in the OBs.Computed tomography(CT),meganetic resonance imaging(MRI),and positron emission tomography(PET)were used to detect the outcomes of anosmia in these studies.Conclusions The changes in OC are greater than those in OB in patients with COVID-19,mainly due to the inflammatory and immune responses in OC.However,fewer changes in OB are due to neurological or vascular disorders.Topical steroid therapy and topical saline can be helpful.
基金supported by Shenzhen Sanming Engineering Project(SZSM202011012)Shenzhen Innovation Science and Technology Committee(JCYJ20180228175358223)National Natural Science Foundation of China(31670742)。
文摘Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.
文摘Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles. Cells of the subventricular zone divide and migrate via the rostral migratory stream to the olfactory bulb where they differentiate into granule and pefiglomerular cells. With the discovery of large-sca^e neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Although many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. In this review we highlight the main studies investigating factors that regulate neurogenesis in the subventricular zone, neuronal migration to the olfactory bulb, neuronal integration into the existing bulbar network and shortly discuss the functional meaning of this process.
基金supported by the National Natural Science Foundation of China(Nos.32271055 and 32070995)the Jiangsu Province Innovative and Entrepreneurial Team Program,and the Guangdong Medical University(No.GDMUB2022048),China.
文摘The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neurons in the OB,mitral/tufted cells encode information such as odor identity and concentration.Recently,the neural strategies and mechanisms underlying odor representation and encoding in the OB have been investigated extensively.Here we review the main progress on this topic.We first review the neurons and circuits involved in odor representation,including the different cell types in the OB and the neural circuits within and beyond the OB.We will then discuss how two different coding strategies—spatial coding and temporal coding—work in the rodent OB.Finally,we discuss potential future directions for this research topic.Overall,this review provides a comprehensive description of our current understanding of how odor information is represented and encoded by mitral/tufted cells in the OB.
基金the National Natural Science Foundation of China(31872771,32070995,and 31900713)the National Demonstration Center for Experimental Basic Medical Science Education(Xuzhou Medical University).
文摘Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca^(2+)signals in genetically-identified neuronal populations.Although fiber photometry is widely used in neuroscience research,the relationship between the recorded Ca^(2+)signals and direct electrophysiological measurements of neural activity remains elusive.Here,we simultaneously recorded odor-evoked Ca^(2+)and electrophysiological signals[single-unit spikes and local field potentials(LFPs)]from mitral/tufted cells in the olfactory bulb of awake,head-fixed mice.Odors evoked responses in all types of signal but the response characteristics(e.g.,type of response and time course)differed.The Ca^(2+)signal was correlated most closely with power in theβ-band of the LFP.The Ca^(2+)signal performed slightly better at odor classification than high-γoscillations,worse than single-unit spikes,and similarly toβoscillations.These results provide new information to help researchers select an appropriate method for monitoring neural activity under specific conditions.
基金The MKE(The Ministry of Knowledge Economy),Korea,under the ITRC(Information Technology Research Center)support program supervised by the NIPA(National IT Industry Promotion Agency) (NIPA-2012-H0301-12-2006)Brain Research Center(BRC)(2012K001127),The MKE(10033634-2012-21)National Research Foundation of Korea(NRF)(2012-0005787)
文摘We characterize the hemodynamic response changes near-infrared spectroscopy （NIRS） during the presentation of in the main olfactory bulb （MOB） of anesthetized rats with three different odorants： （i） plain air as a reference （Blank）, （ii） 2-heptanone （HEP）, and （iii） isopropylbenzene （Ib）. Odorants generate different changes in the concentrations of oxy- hemoglobin. Our results suggest that NIRS technology might be useful in discriminating various odorants in a non-invasive manner using animals with a superb olfactory system.
基金supported by an Australian Postgraduate Award to D.A
文摘The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.
