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Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.
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P J Jastreboff P E Pedersen C A Greer W B Stewart J S Kauer T E Benson G M Shepherd 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(16):5250-5254
A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity. 相似文献
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Lin DM Yang YH Scolnick JA Brunet LJ Marsh H Peng V Okazaki Y Hayashizaki Y Speed TP Ngai J 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(34):12718-12723
How olfactory sensory neurons converge on spatially invariant glomeruli in the olfactory bulb is largely unknown. In one model, olfactory sensory neurons interact with spatially restricted guidance cues in the bulb that orient and guide them to their target. Identifying differentially expressed molecules in the olfactory bulb has been extremely difficult, however, hindering a molecular analysis of convergence. Here, we describe several such genes that have been identified in a screen that compiled microarray data to create a three-dimensional model of gene expression within the mouse olfactory bulb. The expression patterns of these identified genes form the basis of a nascent spatial map of differential gene expression in the bulb. 相似文献
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Richard C. Gerkin Shreejoy J. Tripathy Nathaniel N. Urban 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(42):17083-17088
Mitral/tufted (M/T) cells of the main olfactory bulb transmit odorant information to higher brain structures. The relative timing of action potentials across M/T cells has been proposed to encode this information and to be critical for the activation of downstream neurons. Using ensemble recordings from the mouse olfactory bulb in vivo, we measured how correlations between cells are shaped by stimulus (odor) identity, common respiratory drive, and other cells’ activity. The shared respiration cycle is the largest source of correlated firing, but even after accounting for all observable factors a residual positive noise correlation was observed. Noise correlation was maximal on a ∼100-ms timescale and was seen only in cells separated by <200 µm. This correlation is explained primarily by common activity in groups of nearby cells. Thus, M/T-cell correlation principally reflects respiratory modulation and sparse, local network connectivity, with odor identity accounting for a minor component.Mitral/tufted cells (M/Ts) of the olfactory bulb (OB) receive odor-evoked activity from sensory neurons and transmit it to central brain structures. Thus, understanding how odor information is represented by these neurons’ activity is essential to understanding olfactory coding. Studying coding properties at this stage in the olfactory system is particularly interesting because the small number of M/Ts (∼50,000) compared with sensory neurons (∼10 million) or olfactory cortical neurons (∼2 million) suggests that this stage represents a bottleneck (1).Odor information is encoded in the spatial pattern of activity across the OB (2). However, the timing of M/T activity may also play a crucial role in odor representation. Individual M/Ts fire odor-specific patterns of spikes (3), and spike timing across populations of M/Ts relative to the respiration cycle has been proposed as an olfactory code (4, 5). However, whether odor identity influences the correlation of M/T activity (i.e., the tendency of neurons to spike together) has not been specifically addressed.Ensemble firing patterns better predict odorant identity than do single neuron firing rates alone (6, 7), suggesting the utility of a population timing code. Additionally, learned olfactory behaviors are associated with increased M/T spike synchrony (8), and disrupting this synchrony in insect M/T analogs reduces odor discriminability (9). Furthermore, analysis of neural correlations has informed our understanding of the relationship between neural circuits and population activity and has constrained hypotheses concerning “decoding” of incoming population activity by downstream areas (10).Here, we evaluated how relative M/T timing depends upon odor identity and timing, respiration phase (inhalation/exhalation), and other neurons’ spiking. Correlated spiking in the OB is familiar (11, 12), but how these correlations depend on such variables is unknown. Correlations may originate in common stimulus or respiration phase preferences (“signal correlation”). Cell pairs’ spiking may also exhibit covariation beyond that predicted from such preferences (“noise correlation,” Rnoise) and may reflect correlated input noise or synaptic coupling between cells (13, 14). In Xenopus and Drosophila, M/Ts and their analogs exhibit significant noise correlation (15, 16). However, the origins, magnitude, and scope of such correlations have not been described in the mammalian OB.Critically, correlation driven by respiration or population activity in the local circuit has not been estimated, yet this is required to understand the sources and possible functions of OB correlations, and the theoretical coding capacity and mechanisms of OB neural ensembles (17, 18). We contrast our analysis to the computation of trial-averaged population response correlations (i.e., “pattern correlations”). Our approach is more analogous to that of, for example, Kazama and Wilson (16): We address within-trial spike-timing correlations between cell pairs rather than correlations between trial-averaged responses to different odorants (19).We made ensemble recordings from mouse OB during odor presentation. From these recordings we isolated contributions of several olfactory variables to spiking in individual neurons and to intercell correlation. Respiration phase tuning accounts for much correlation, whereas some nearby cell pairs exhibit small, positive Rnoise, independent of the stimulus. Conditional on the activity of the larger population, functional coupling between cells is sparse overall, with significant implications for olfactory coding. 相似文献
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Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. 总被引:19,自引:0,他引:19
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M Yokoi K Mori S Nakanishi 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(8):3371-3375
Mitral/tufted cells (M/T cells) and granule cells form reciprocal dendrodendritic synapses in the main olfactory bulb; the granule cell is excited by glutamate from the M/T cell and in turn inhibits M/T cells by gamma-aminobutyrate. The trans-synaptically excited granule cell is thought to induce lateral inhibition in neighboring M/T cells and to refine olfactory information. It remains, however, elusive how significantly and specifically this synaptic regulation contributes to the discrimination of different olfactory stimuli. This investigation concerns the mechanism of olfactory discrimination by single unit recordings of responses to a series of normal aliphatic aldehydes from individual rabbit M/T cells. This analysis revealed that inhibitory responses are evoked in a M/T cell by a defined subset of odor molecules with structures closely related to the excitatory odor molecules. Furthermore, blockade of the reciprocal synaptic transmission by the glutamate receptor antagonist or the gamma-aminobutyrate receptor antagonist markedly suppressed the odor-evoked inhibition, indicating that the inhibitory responses are evoked by lateral inhibition via the reciprocal synaptic transmission. The synaptic regulation in the olfactory bulb thus greatly enhances the tuning specificity of odor responses and would contribute to discrimination of olfactory information. 相似文献
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A dendrodendritic reciprocal synapse provides a recurrent excitatory connection in the olfactory bulb 总被引:2,自引:0,他引:2
Didier A Carleton A Bjaalie JG Vincent JD Ottersen OP Storm-Mathisen J Lledo PM 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(11):6441-6446
Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action of glutamate released from mitral cells (MC, olfactory bulb relay neurons). According to this hypothesis, glutamate spills over from dendrodendritic synapses formed between MC and granule cells (GC, olfactory bulb interneurons) to activate neighboring MC. The excitation of MC is balanced by a strong inhibition from GC. Here we show that MC excitation is caused by glutamate released from bulbar interneurons located in the GC layer. These reciprocal synapses depend on an unusual, 2-amino-5-phosphonovaleric acid-resistant, N-methyl-d-aspartate receptor. This type of feedback excitation onto relay neurons may strengthen the original sensory input signal and further extend the function of the dendritic microcircuit within the main olfactory bulb. 相似文献
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Willhite DC Nguyen KT Masurkar AV Greer CA Shepherd GM Chen WR 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(33):12592-12597
Olfactory sensory neurons converge onto glomeruli in the olfactory bulb (OB) to form modular information processing units. Similar input modules are organized in translaminar columns for other sensory modalities. It has been less clear in the OB whether the initial modular organization relates to a columnar structure in the deeper layers involved in local circuit processing. To probe synaptic connectivity in the OB, we injected a retrograde-specific strain of the pseudorabies virus into the rat OB and piriform cortex. The viral-staining patterns revealed a striking columnar organization that extended across all layers of the OB from the glomeruli to the deep granule cell layer. We hypothesize that the columns represent an extension of the glomerular unit. Specific patterning was observed, suggesting selective, rather than distance-dependent, center-surround connectivity. The results provide a previously undescribed basis for interpreting the synaptic connections between mitral and granule cells within the context of a columnar organization in the OB and have implications for olfactory coding and network organization. 相似文献
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Michele Migliore Francesco Cavarretta Addolorata Marasco Eleonora Tulumello Michael L. Hines Gordon M. Shepherd 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(27):8499-8504
How the olfactory bulb organizes and processes odor inputs through fundamental operations of its microcircuits is largely unknown. To gain new insight we focus on odor-activated synaptic clusters related to individual glomeruli, which we call glomerular units. Using a 3D model of mitral and granule cell interactions supported by experimental findings, combined with a matrix-based representation of glomerular operations, we identify the mechanisms for forming one or more glomerular units in response to a given odor, how and to what extent the glomerular units interfere or interact with each other during learning, their computational role within the olfactory bulb microcircuit, and how their actions can be formalized into a theoretical framework in which the olfactory bulb can be considered to contain “odor operators” unique to each individual. The results provide new and specific theoretical and experimentally testable predictions.The organization of olfactory bulb network elements and their synaptic connectivity has evolved to subserve special computational functions needed for odor detection and recognition (1–5). Key to this organization are the olfactory glomeruli, collecting input from olfactory receptor neuron subsets. These connect to the dendrites of mitral, tufted, and periglomerular cells, and the mitral and tufted cells in turn connect to granule cells. We term these interconnected cells a cluster, and a cluster related to a given glomerulus is a glomerular unit (GU), often visualized as a column of granule cell bodies located below a glomerulus (6, 7). The existence of such GUs has also been suggested from 2-deoxyglucose (8) and voltage-sensitive dye studies (9).Understanding the neural basis of odor processing therefore requires understanding the computational functions and role of GUs. These issues, which are difficult or impossible in experiments, can be conveniently explored using realistic computational models, provided they are able to explain and reproduce crucial experimental findings on glomerular clusters or units.Analyzing synaptic interactions between cells with overlapping dendrites requires modeling in real 3D space. Scaling up to the network level further requires scaling up realistic structural and functional properties to many thousands of cells (10). Building on this unique approach, we show that this model generates columnar clusters of cells related to individual glomeruli, as in the experiments, and further demonstrates mechanisms of odor processing within and between the GUs. Finally, interpreting this network activity requires a theoretical framework, incorporating distributed activated glomeruli within the global network, for which we introduce the concept of the odor operator. The results provide a basis for extension to the glomerular level on the one hand and interactions with olfactory cortex on the other. 相似文献
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Nikonov AA Finger TE Caprio J 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(51):18688-18693
We report electrophysiological evidence that a simple odotopy, the spatial mapping of different odorants, is maintained above the level of the olfactory bulb (OB). Three classes of biologically relevant odorants for fish are processed in distinct regions of the forebrain (FB) in the channel catfish. Feeding cues, mainly amino acids and nucleotides, are represented in lateral, pallial portions of the FB, equivalent to the olfactory cortex of amniote vertebrates, whereas social signals mediated by bile salts are represented in medial FB centers, possibly homologous to portions of the amygdala. As in the OB, the different odorant classes map onto different territories; however, the response properties of units of the olfactory areas of the FB do not simply mirror those of the OB. For some units, distinctive response properties emerged, because the FB is the first center where odors subserving a common behavioral function (i.e., food function) converge. 相似文献
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Alexia Nunez-Parra Robert K. Maurer Krista Krahe Richard S. Smith Ricardo C. Araneda 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(36):14777-14782
Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.Sensory information from the external world is integrated through a series of feed-forward stages toward higher cognitive cortical areas. At these different stages, sensory perception can be regulated by an individual’s internal state to enhance meaningful information relative to less valuable information associated with different behavioral tasks (1, 2). Unlike other sensory systems, peripheral sensory input onto principal neurons in the olfactory bulb (OB) is relayed directly to olfactory cortices and subcortical nuclei, bypassing the thalamus (3). The OB is the first stage in which extensive fine-tuning and processing of olfactory information occurs (4). This processing involves integration of bottom-up and top-down information by the most abundant OB cell type, the granule cells (GCs). GCs establish most of their connections with output neurons, the mitral and tufted cells (MCs herein), through the ubiquitous dendrodendritic synapses (DDS) and with a few other subtypes of interneurons (5–8). Importantly, the interaction between MCs and GCs is thought to give rise to network oscillations in the OB that are associated with MC firing synchronization, adding an important time component to olfactory processing (9–13).In analogy with the regulation of thalamic neurons by cortical inputs, GCs receive important feedback regulation from cortical and subcortical projection areas of MCs and afferents from neuromodulatory systems (3, 14–16). Activation of these feedback projections and neuromodulatory systems increases GC excitability (14, 17, 18), thus increasing GABA-mediated inhibition at DDS and regulating olfactory processing. For example, regulation of GC-mediated inhibition by noradrenaline in the main olfactory bulbs (MOBs) and accessory olfactory bulbs (AOBs) has been shown to affect a range of olfactory behaviors including odor discrimination and more complex behaviors such as memory formation during mating (19). In addition, other studies have indicated an extensive innervation by GABAergic fibers originating in the horizontal limb of the diagonal band of Broca (HDB) and magnocellular preoptic area (MCPO) that preferentially targets the GC layer in the OB (20, 21). Interestingly, the HDB/MCPO is also the origin of the cholinergic afferent fibers that target the OB (22), and this cholinergic input has been shown to have an important influence in olfactory processing (23). Although mechanisms that promote excitation of GCs have been studied extensively, the mechanisms that promote inhibition of GCs have received less attention. The existence of a descending inhibitory input suggests that regulation of GCs by afferent inhibition also can modulate olfactory processing. Previous studies indicated that direct stimulation of HDB/MCPO can inhibit neuronal activity in the OB (24); however, the presence of cholinergic projections from this region has confounded the interpretation of these observations. Here, we expressed channelrhodopsin (ChR2) exclusively in inhibitory neurons of the HDB/MCPO to control GABA release in the OB selectively and to determine its influence on GC function and olfactory discrimination. 相似文献
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Mapping of odor-related neuronal activity in the olfactory bulb by high-resolution 2-deoxyglucose autoradiography. 总被引:4,自引:2,他引:4
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D Lancet C A Greer J S Kauer G M Shepherd 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(2):670-674
The spatial distribution of odor-induced neuronal activity in the olfactory bulb, the first relay station of the olfactory pathway, is believed to reflect important aspects of chemosensory coding. We report here the application of high-resolution 2-deoxyglucose autoradiography to the mapping of spatial patterns of metabolic activity at the level of single neurons in the olfactory bulb. It was found that glomeruli, which are synaptic complexes containing the first synaptic relay, tend to be uniformly active or inactive during odor exposure. Differential 2-deoxyglucose uptake was also observed in the somata of projection neurons (mitral cells) and interneurons (periglomerular and granule cells). This confirms and extends our previous studies in which odor-specific laminar and focal uptake patterns were revealed by the conventional x-ray film 2-deoxyglucose method due to Sokoloff and colleagues [Sokoloff, L., Reivich, M., Kennedy, C., DesRosiers, M. H., Patlak, C. S., Pettigrew, K. D., Sakurada, O. & Shinohara, M. (1977) J. Neurochem. 28, 897--916]. Based on results obtained by the two methods, it is suggested that the glomerulus as a whole serves as a functional unit of activity. The high-resolution results are interpreted in terms of the well-characterized synaptic organization of the olfactory bulb and also serve to illustrate the capability of the 2-deoxyglucose autoradiographic technique to map metabolic activity in single neurons of the vertebrate central nervous system. 相似文献
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Clinical Rheumatology - Among the other symptoms, impaired olfactory function such as odor identification, threshold, and discrimination have been reported in patients with fibromyalgia syndrome... 相似文献
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《Annales d'endocrinologie》2017,78(5):455-461
ObjectiveThe aim of this retrospective study was to perform magnetic resonance imaging assessment of olfactory pathway and skull base abnormalities in Kallmann syndrome (KS) patients with hypogonadotropic hypogonadism and olfaction disorder.MethodsMagnetic resonance brain patterns were retrospectively studied in 19 patients clinically classified as KS. Qualitative assessment of olfactory bulb region comprised bulb atrophy and rectus and medial orbital gyrus ptosis; quantitative assessment measured olfactory fossa depth and width, sulcus depth and ethmoid angle. Results were compared to an age- and sex-matched control population (n = 19) with no impairment in the region of interest. Sixteen of the 19 KS patients were genetically screened for mutations associated with KS.ResultsOn the above qualitative criteria, 15 of the 19 patients presented either unilateral (n = 2) or bilateral (n = 13) olfactory bulb agenesis; 16 showed tract agenesis and 16 showed gyrus malformation (ptosis or absence). On the quantitative criteria, 18 of the 19 patients showed abnormal sulcus depth and/or olfactory fossa malformation and/or abnormal ethmoid angle.ConclusionThe presence of malformation abnormalities in the olfactory fossae of 18 of the 19 patients appears to be a key factor for etiological diagnosis of hypogonadotropic hypogonadism, and should enable targeted study of genes involved in KS. 相似文献
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Chaigneau E Oheim M Audinat E Charpak S 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(22):13081-13086
Analysis of the spatiotemporal coupling between neuronal activity and cerebral blood flow requires the precise measurement of the dynamics of RBC flow in individual capillaries that irrigate activated neurons. Here, we use two-photon microscopy in vivo to image individual RBCs in glomerular capillaries in the rat dorsal olfactory bulb. We find that odor stimulation evokes capillary vascular responses that are odorant- and glomerulus-specific. These responses consist of increases as well as decreases in RBC flow, both resulting from independent changes in RBC velocity or linear density. Finally, measuring RBC flow with micrometer spatial resolution and millisecond temporal resolution, we demonstrate that, in olfactory bulb superficial layers, capillary vascular responses precisely outline regions of synaptic activation. 相似文献
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Li A Gong L Xu F 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(12):5087-5092
It is critical for normal brains to perceive the external world precisely and accurately under ever-changing operational conditions, yet the mechanisms underlying this fundamental brain function in the sensory systems are poorly understood. To address this issue in the olfactory system, we investigated the responses of olfactory bulbs to odor stimulations under different brain states manipulated by anesthesia levels. Our results revealed that in two brain states, where the spontaneous baseline activities differed about twofold based on the local field potential (LFP) signals, the levels of neural activities reached after the same odor stimulation had no significant difference. This phenomenon was independent of anesthetics (pentobarbital or chloral hydrate), stimulating odorants (ethyl propionate, ethyl butyrate, ethyl valerate, amyl acetate, n-heptanal, or 2-heptanone), odor concentrations, and recording sites (the mitral or granular cell layers) for LFPs in three frequency bands (12-32 Hz, 33-64 Hz, and 65-90 Hz) and for multiunit activities. Furthermore, the activity patterns of the same stimulation under these two brain states were highly similar at both LFP and multiunit levels. These converging results argue the existence of mechanisms in the olfactory bulbs that ensure the delivery of peripheral olfactory information to higher olfactory centers with high fidelity under different brain states. 相似文献
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Mandairon N Stack C Kiselycznyk C Linster C 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(36):13543-13548
A number of electrophysiological experiments have shown that odor exposure alone, unaccompanied by behavioral training, changes the response patterns of neurons in the olfactory bulb. As a consequence of these changes, across mitral cells in the olfactory bulb, individual odors should be better discriminated because of previous exposure. We have previously shown that a daily 2-h exposure to odorants during 2 weeks enhances rats' ability to discriminate between chemically similar odorants. Here, we first show that the perception of test odorants is only modulated by enrichment with odorants that activate at least partially overlapping regions of the olfactory bulb. Second, we show that a broad activation of olfactory bulb neurons by daily local infusion of NMDA into both olfactory bulbs enhances the discrimination between chemically related odorants in a manner similar to the effect of daily exposure to odorants. Computational modeling of the olfactory bulb suggests that activity-dependent plasticity in the olfactory bulb can support the observed modulation in olfactory discrimination capability by enhancing contrast and synchronization in the olfactory bulb. Last, we show that blockade of NMDA receptors in the olfactory bulb impairs the effects of daily enrichment, suggesting that NMDA-dependent plasticity is involved in the changes in olfactory processing observed here. 相似文献
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Mizrahi A Lu J Irving R Feng G Katz LC 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(6):1912-1917
As a consequence of adult neurogenesis, the olfactory bulb (OB) receives a continuous influx of newborn neurons well into adulthood. However, their rates of generation and turnover, the factors controlling their survival, and how newborn neurons intercalate into adult circuits are largely unknown. To visualize the dynamics of adult neurogenesis, we produced a line of transgenic mice expressing GFP in approximately 70% of juxtaglomerular neurons (JGNs), a population that undergoes adult neurogenesis. Using in vivo two-photon microscopy, time-lapse analysis of identified JGN cell bodies revealed a neuronal turnover rate of approximately 3% of this population per month. Although new neurons appeared and older ones disappeared, the overall number of JGNs remained constant. This approach provides a dynamic view of the actual appearance and disappearance of newborn neurons in the vertebrate central nervous system, and provides an experimental substrate for functional analysis of adult neurogenesis. 相似文献