Individual Glomeruli Research Articles

Odor-evoked gene regulation and visualization in olfactory receptor neurons

Odorant-evoked activity contributes to olfactory epithelium organization and axon targeting. We examined the consequences on gene expression of a genetic disruption of the channel responsible for olfactory transduction. Genes encoding calcium-binding EF-hand motifs, were among the most highly regulated transcripts consistent with the central role of Ca 2+ influx in neuronal depolarization. Several genes encoding integral membrane proteins are also highly regulated. One gene, Lrrc3b, was regulated more than 10-fold by odorant activity. Changes in expression occur within thirty minutes and are maintained for several hours. In genetic disruptions of Lrrc3b, a Lrrc3b-promoter-driven reporter adopts the activity-regulated expression of the endogenous gene. Individual olfactory glomeruli have a wide spectrum of activity levels that can be modulated by altering odor exposure. The Lrrc3b reporter mouse permits direct assessment of activity in identified glomeruli. In stable odorant environments, activity-regulated proteins provide a characteristic signature that is correlated with the olfactory receptor they express.

Cortical representation of olfactory bulb input revealed by retrograde mono-transsynaptic labeling

In the mouse olfactory system, more than 1000 classes of olfactory receptor neurons(ORNs) each sends convergent axonal projections into a pair of specific glomeruli in the olfactory bulb (OB), creating a space map for odor detection. Mitral/tufted cells receive ORN inputs from individual glomeruli and project axons to the olfactory cortex. How the olfactory map in the OB is represented in the cortex is largely unknown. Here we combine a retrograde mono-transsynaptic labeling technique with mouse genetics such that we can precisely control spatial location, number and cell type of starter cortical neurons. We found that individual cortical neurons receive mitral cells representing multiple glomeruli, demonstrating a direct information convergence. Cortical neurons in highly restricted areas receive inputs from glomeruli that spread widely in the olfactory bulb. Quantitative analyses revealed that the space map in the OB is differentially represented in the anterior olfactory nucleus, amygdala and piriform cortex. Finally, our genetically regulable transsynaptic labeling method can be widely applied to mapping connections in many parts of the nervous system in mice.

From chemical to receptive space

Event Abstract Back to Event From chemical to receptive space Jan Sölter1*, Hartwig Spors2, Jan Schumacher2 and Michael Schmuker1 1 FU Berlin, Institut für Biologie, AG Neuroinformatik, Germany 2 Max Planck Institut für Biophysik, Department of Molecular Neurogenetics, Germany In a high throughput screening process we determine the in vivo response of glomeruli in the mouse olfactory bulb to different odors using intrinsic signal optical imaging. On this basis we identify the receptive range of individual glomeruli and predict further activating odors using pattern recognition algorithms: odor molecules are described by physio-chemical descriptors on which Support Vector Machines are trained to distinguish activating and non-activating molecules. The optimal set of descriptors is obtained by using an Evolutionary Algorithm. In an iterative scheme, the hypotheses are validated or falsified by imaging experiments using previously untested odors. In a first iteration for a GFP labeled glomerulus three new potential ligands were identified. Employing the imaging and prediction results of individual glomeruli our goal is to obtain a molecular property map of the olfactory bulb. Keywords: computational neuroscience Conference: Bernstein Conference on Computational Neuroscience, Berlin, Germany, 27 Sep - 1 Oct, 2010. Presentation Type: Poster Abstract Topic: Bernstein Conference on Computational Neuroscience Citation: Sölter J, Spors H, Schumacher J and Schmuker M (2010). From chemical to receptive space. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.fncom.2010.51.00111 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Sep 2010; Published Online: 23 Sep 2010. * Correspondence: Dr. Jan Sölter, FU Berlin, Institut für Biologie, AG Neuroinformatik, Berlin, Germany, j.soelter@fu-berlin.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jan Sölter Hartwig Spors Jan Schumacher Michael Schmuker Google Jan Sölter Hartwig Spors Jan Schumacher Michael Schmuker Google Scholar Jan Sölter Hartwig Spors Jan Schumacher Michael Schmuker PubMed Jan Sölter Hartwig Spors Jan Schumacher Michael Schmuker Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

In vivo detection of individual glomeruli in the rodent olfactory bulb using manganese enhanced MRI

MRI contrast based on relaxation times, proton density, or signal phase have been applied to delineate neural structures in the brain. However, neural units such as cortical layers and columns have been difficult to identify using these methods. Manganese ion delivered either systemically or injected directly has been shown to accumulate specifically within cellular areas of the brain enabling the differentiation of layers within the hippocampus, cortex, cerebellum, and olfactory bulb in vivo. Here we show the ability to detect individual olfactory glomeruli using manganese enhanced MRI (MEMRI). Glomeruli are anatomically distinct structures (∼150 μm in diameter) on the surface of the olfactory bulb that represent the first processing units for olfactory sensory information. Following systemic delivery of MnCl2 we used 3D-MRI with 50 μm isotropic resolution to detect discrete spots of increased signal intensity between 100 and 200 μm in diameter in the glomerular layer of the rat olfactory bulb. Inflow effects of arterial blood and susceptibility effects of venous blood were suppressed and were evaluated by comparing the location of vessels in the bulb to areas of manganese enhancement using iron oxide to increase vessel contrast. These potential vascular effects did not explain the contrast detected. Nissl staining of individual glomeruli were also compared to MEMRI images from the same animals clearly demonstrating that many of the manganese enhanced regions corresponded to individual olfactory glomeruli. Thus, MEMRI can be used as a non-invasive means to detect olfactory glomeruli for longitudinal studies looking at neural plasticity during olfactory development or possible degeneration associated with disease.

Three-dimensional antennal lobe atlas of the oriental fruit moth, Cydia molesta (Busck) (Lepidoptera: Tortricidae): comparison of male and female glomerular organization

The oriental fruit moth Cydia molesta is an important pest and the behavioural role of olfactory signals such as pheromones and plant volatiles have been studied extensively in both sexes. To understand odour processing further, however, detailed knowledge of the anatomy of the olfactory system is crucial. In the present study, an atlas of the antennal lobe (AL) is presented based on the three-dimensional reconstructions of both ALs of three male and three female brains by means of neuroanatomical and computational approaches. We identified 48-49 "ordinary" glomeruli and one large glomerulus situated at the entrance of the antennal nerve in males, and 49-52 "ordinary" glomeruli and one large glomerulus in the ventro-medial part of the AL in females. Anomalous supernumerary, anomalous missing and sexually dimorphic glomeruli were found in the studied individuals in greater numbers than in other lepidopteran species. Male and female maps were compared with respect to glomerular size and position with 45 glomeruli being matched, indicating a conserved glomerular pattern between the sexes. Three additional glomeruli were sexually dimorphic in size and five male-specific and six female-specific glomeruli were also found. Palp backfills resulted in the staining of a unique glomerulus in both sexes identified as the sexually dimorphic glomerulus 45. This glomerulus was never stained from antennal backfills, which stained the other glomeruli of the AL. The three-dimensional atlas can now be used to elucidate the functional role of individual glomeruli in both sexes of C. molesta.

The effect of castration and androgen treatment on glomerular volume in mice.

The mouse kidney is specially responsive to the withdrawal or administration of androgens. Castration markedly reduces renal weight in male mice, whereas androgen treatment restores normal kidney size. The present study demonstrates that these changes in whole kidney size are accompanied by parallel changes in total glomerular volume. The results indicate that the individual glomeruli change their volume during the experiments. The observed changes in the kidney weight and total volume of glomeruli after castration did not affect the plasma level of creatinine. Smaller kidney with less total volume of glomeruli can preserve internal environment.

Select Drosophila glomeruli mediate innate olfactory attraction and aversion

Fruit flies exhibit robust attraction to food odors, which usually excite multiple glomeruli. To understand how the representation of such odors leads to behavior, we used genetic tools to dissect the contribution of each activated glomerulus. Apple cider vinegar triggers robust innate attraction at a relatively low concentration, which activates six glomeruli. By silencing individual glomeruli, we found that the absence of activity in two glomeruli, DM1 and VA2, markedly reduced attraction. Conversely, when each of these two glomeruli was selectively activated, flies exhibited as robust an attraction to vinegar as wild type flies. Notably, a higher concentration of vinegar excites an additional glomerulus and is less attractive to flies. Here we show that the activation of the additional glomerulus is necessary and sufficient to mediate the behavioral switch. Together, these results indicate that individual glomeruli, rather than the entire pattern of active glomeruli, mediate innate behavioral output.

Heterogeneous Sensory Innervation and Extensive Intrabulbar Connections of Olfactory Necklace Glomeruli

The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB) targets of an olfactory sensory neuron (OSN) subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO2. In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR), we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.

Olfactory psychometric functions for homologous 2-ketones

We measured concentration-detection (i.e., psychometric) odor functions for the homologous ketones propanone (acetone), 2-pentanone, 2-heptanone, and 2-nonanone. Under a forced-choice procedure, stimuli were presented via an 8-channel air-dilution olfactometer that allowed natural sampling of the odorant and whose output was quantified by gas chromatography. Subjects (17–22 per compound) comprised young adults from both genders, all normosmics and nonsmokers. A sigmoid (logistic) equation tightly fitted group and individual functions. The odor detection threshold (ODT) was the concentration detectable at halfway ( P = 0.5) between chance ( P = 0.0) and perfect ( P = 1.0) detection. Odor sensitivity increased (i.e., thresholds decreased) from acetone to heptanone, remaining constant for nonanone. This relative trend was also observed in previous work and in odor thresholds compilations, but the absolute ODTs obtained here were consistently at the lower end of those reported before. Interindividual variability of ODTs was about 1 order of magnitude. These odor functions measured behaviorally in humans were obtained at vapor concentrations 1000 times lower than functions measured via activation, with similar 2-ketones, of receptor neurons converging into individual olfactory glomeruli of mice, visualized with calcium sensitive dyes. Odorant concentrations presented as vapors (as in behavioral studies) and those presented as liquids (as in cellular/tissue studies) can be rendered equivalent via liquid–vapor partition coefficients and, then, compared in relative olfactory potency. These comparisons can reveal how sensitivity is progressively shaped across levels of the neural pathway.

Constancy and variability of glomerular organization in the antennal lobe of the silkmoth

We investigated the anatomical organization of glomeruli in the antennal lobes (ALs) of male silkmoths. We reconstructed 10 different ALs and established an identification procedure for individual glomeruli by using size, shape, and position relative to anatomical landmarks. Quantitative analysis of these morphological characteristics supported the validity of our identification strategy. The glomerular organization of the ALs was roughly conserved between different ALs. However, we found individual variations that were reproducibly observed. The combination of a digital atlas with other experimental techniques, such as electrophysiology, optical imaging, and genetics, should facilitate a more in-depth analysis of sensory information processing in silkmoth ALs.

Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension inBr/+ adult mice

The Br/+ mutant mouse displays decreased embryological expression of the homeobox transcription factor Six2, resulting in hertitable renal hypoplasia. The purpose of this study was to characterize the renal physiological consequences of embryonic haploinsuffiency of Six2 by analyzing renal morphology and function in the adult Br heterozygous mutant. Adult Br/+ kidneys weighed 50% less than those from wild-type mice and displayed glomerulopathy. Stereological analysis of renal glomeruli showed that Br/+ kidneys had an average of 88% fewer glomeruli than +/+ kidneys, whereas individual glomeruli in Br/+ mice maintained an average volume increase of 180% compared with normal nephrons. Immunostaining revealed increased levels of endothelin-1 (ET-1), endothelin receptors A (ET(A)) and B (ET(B)), and Na-K-ATPase were present in the dilated renal tubules of mutant mice. Physiological features of chronic renal failure (CRF) including elevated mean arterial pressure, increased plasma creatinine, and dilute urine excretion were measured in Br/+ mutant mice. Electron microscopy of the Br/+ glomeruli revealed pathological alterations such as hypercellularity, extracellular matrix accumulation, and a thick irregular glomerular basement membrane. These results indicate that adult Br/+ mice suffer from CRF associated with reduced nephron number and renal hypoplasia, as well as glomerulopathy. Defects are associated with embryological deficiencies of Six2, suggesting that proper levels of this protein during nephrogenesis are critical for normal glomerular development and adult renal function.

Relating the Neural Representation and Perceptual Quality of Olfactory Stimuli

Event Abstract Back to Event Relating the Neural Representation and Perceptual Quality of Olfactory Stimuli John P. McGann1* 1 Rutgers University, Department of Psychology, United States The mouse olfactory bulb provides a powerful system for exploring the olfactory system because it permit the direct observation of physiological responses to odorants on both the population and single-cell levels while relating those responses to the corresponding perception of the odorant using behavioral olfactory psychophysical experimentation. Fig. 1A shows a fluorescence image of the right olfactory bulb of an anesthetized mouse expressing the exocytosis indicator synaptopHluorin [1] in the axon terminals of its olfactory receptor neurons (ORNs). The image shows the dorsal surface of the bulb visualized in vivo through a cranial window. Note that individual olfactory bulb glomeruli are visible in both the lower (left) and higher (right) magnification views. Fig. 1B (left) illustrates how the presentation of the odorant methyl valerate induces an increase in fluorescence (indicating transmitter release from ORN terminals) in a subset of the glomeruli shown in 1A (right). This pattern of response is odorant-specific, thus serving as the primary sensory representation of the odorant. In this session I will show how changes in this sensory representation may be induced experimentally, though pharmacological manipulation or sensory experience, and how these changes can be linked to olfactory perception. Fig. 1B illustrates how the application of the GABAB receptor antagonist CGP35348 (which blocks the GABA-mediated presynaptic inhibition of neurotransmitter release from ORN terminals) alters the representation of methyl valerate by increasing the magnitude of odor-evoked synaptic input without changing the relative responses across glomeruli [2]. In separate behavioral experiments, mice received bilateral infusions of CGP while performing behavioral tasks designed to quantify their perception of odor intensity and to evaluate their ability to discriminate between chemically similar odorants. The results demonstrate that CGP infusion produces changes in olfactory perceptions that are predictable from its effects on the neurophysiology of odorant responses. These experiments show how this combination of experimental techniques can successfully link the neural representation of odorants with the behaviorally-observed perception of odor intensity and quality. fig1

Manganese enhanced MRI reveals functional circuitry in response to odorant stimuli

To investigate the circuitry involved in detecting odorants in the rodent brain, we developed a method using manganese-enhanced MRI (MEMRI) to map the flow of neural information from the olfactory sensory neurons (OSNs) to the central layers of the olfactory bulb. Studies have shown that Mn 2+ enters active neurons and is transported anterogradely to axon terminals where it can cross synapses to functionally trace neural networks. Thus, by delivering MnCl 2 directly into the nasal cavity of mice and then exposing them to defined odorants, Mn 2+ is preferentially taken up by activated OSNs. Using the time course of the MRI signal, we generated maps of Mn 2+ accumulation in the olfactory bulb for both glomerular and mitral cell layers. Results demonstrated that overlapping yet distinct enhancement patterns were produced by exposure to either octanal, acetophenone, or carvone. Notably, areas of Mn 2+ accumulation in the mitral cell layer were similar to those in the glomerular layer consistent with neural information that passes from specific OSNs to specific mitral cells. Finally, by correlating specific Mn 2+ signal peaks to genetically labeled glomeruli that are known to be activated by the odorant octanal, we show that MEMRI maps can be resolved at the level of individual glomeruli.

MRI of the basement membrane using charged nanoparticles as contrast agents

The integrity of the basement membrane is essential for tissue cellular growth and is often altered in disease. In this work a method for noninvasively detecting the structural integrity of the basement membrane, based on the delivery of cationic iron-oxide nanoparticles, was developed. Cationic particles accumulate due to the highly negative charge of proteoglycans in the basement membrane. The kidney was used to test this technique because of its highly fenestrated endothelia and well-established disease models to manipulate the basement membrane charge barrier. After systemic injection of cationic or native ferritin (CF or NF) in rats, ex vivo and in vivo MRI showed selective accumulation of CF, but not NF, causing a 60% reduction in signal intensity in cortex at the location of individual glomeruli. Immunofluorescence and electron microscopy demonstrated that this CF accumulation was localized to the glomerular basement membrane (GBM). In a model of GBM breakdown during focal and segmental glomerulosclerosis, MRI showed reduced single glomerular accumulation of CF, but a diffuse accumulation of CF in the kidney tubules caused by leakage of CF through the glomerulus. Cationic contrast agents can be used to target the basement membrane and detect the breakdown of the basement membrane in disease.

Activity-Dependent Plasticity in an Olfactory Circuit

Olfactory sensory neurons (OSNs) form synapses with local interneurons and second-order projection neurons to form stereotyped olfactory glomeruli. This primary olfactory circuit is hard-wired through the action of genetic cues. We asked whether individual glomeruli have the capacity for stimulus-evoked plasticity by focusing on the carbon dioxide (CO2) circuit in Drosophila. Specialized OSNs detect this gas and relay the information to a dedicated circuit in the brain. Prolonged exposure to CO2 induced a reversible volume increase in the CO2-specific glomerulus. OSNs showed neither altered morphology nor function after chronic exposure, but one class of inhibitory local interneurons showed significantly increased responses to CO2. Two-photon imaging of the axon terminals of a single PN innervating the CO2 glomerulus showed significantly decreased functional output following CO2 exposure. Behavioral responses to CO2 were also reduced after such exposure. We suggest that activity-dependent functional plasticity may be a general feature of the Drosophila olfactory system.

Glomerular Volume and Clinicopathologic Features Related to Disease Severity in Renal Biopsies of African Americans and Whites in the Southeastern United States

Context. - African Americans have a 4-fold greater risk than whites for developing end-stage renal disease. Glomerulomegaly, possibly related to obesity, has been identified in high-risk populations and is suggested to be a marker for end-stage renal disease risk. Objective. - To investigate differences in glomerular size and patient clinical characteristics at the time of renal biopsy for the major diseases contributing to end-stage renal disease. Design. - Mean glomerular tuft volumes were estimated by the Weibel-Gomez method ( 1964) in native renal biopsies of 203 African American and 100 white patients 18 years of age and older by point counting on a stereologic grid. Glomerulosclerosis was graded on individual glomeruli from 0 to 4, and a glomerular sclerosis index was calculated for each biopsy. Relationships between the mean volume of nonsclerotic glomeruli, age, sex, race, sclerosis index, cortical fibrosis, estimated glomerular filtration rate, body mass index, and disease diagnosis were analyzed. Results. - Racial differences in mean volume of nonsclerotic glomeruli and body mass index were not significant in any disease category, and African Americans had more severe disease as determined by sclerosis index, cortical fibrosis, and estimated glomerular filtration rate only in focal segmental glomerulosclerosis. For all patients, increased sclerosis index and cortical fibrosis and lower estimated glomerular filtration rate were best predicted by increased age ( P < .001). Conclusions. - For approximately the same severity of disease, African Americans were 10 years or more younger than whites with the difference being seen in all disease categories except membranous glomerulonephritis and diabetes. Glomerulomegaly relative to whites was not a distinguishing feature of African American renal biopsies.

Glomerular Volume and Clinicopathologic Features Related to Disease Severity in Renal Biopsies of African Americans and Whites in the Southeastern United States

African Americans have a 4-fold greater risk than whites for developing end-stage renal disease. Glomerulomegaly, possibly related to obesity, has been identified in high-risk populations and is suggested to be a marker for end-stage renal disease risk. To investigate differences in glomerular size and patient clinical characteristics at the time of renal biopsy for the major diseases contributing to end-stage renal disease. Mean glomerular tuft volumes were estimated by the Weibel-Gomez method (1964) in native renal biopsies of 203 African American and 100 white patients 18 years of age and older by point counting on a stereologic grid. Glomerulosclerosis was graded on individual glomeruli from 0 to 4, and a glomerular sclerosis index was calculated for each biopsy. Relationships between the mean volume of nonsclerotic glomeruli, age, sex, race, sclerosis index, cortical fibrosis, estimated glomerular filtration rate, body mass index, and disease diagnosis were analyzed. Racial differences in mean volume of nonsclerotic glomeruli and body mass index were not significant in any disease category, and African Americans had more severe disease as determined by sclerosis index, cortical fibrosis, and estimated glomerular filtration rate only in focal segmental glomerulosclerosis. For all patients, increased sclerosis index and cortical fibrosis and lower estimated glomerular filtration rate were best predicted by increased age (P < .001). For approximately the same severity of disease, African Americans were 10 years or more younger than whites with the difference being seen in all disease categories except membranous glomerulonephritis and diabetes. Glomerulomegaly relative to whites was not a distinguishing feature of African American renal biopsies.

Response profiles to amino acid odorants of olfactory glomeruli in larval Xenopus laevis

Glomeruli in the vertebrate olfactory bulb (OB) appear as anatomically discrete modules receiving direct input from the olfactory epithelium (OE) via axons of olfactory receptor neurons (ORNs). The response profiles with respect to amino acids (AAs) of a large number of ORNs in larval Xenopus laevis have been recently determined and analysed. Here we report on Ca(2+) imaging experiments in a nose-brain preparation of the same species at the same developmental stages. We recorded responses to AAs of glomeruli in the OB and determined the response profiles to AAs of individual glomeruli. We describe the general features of AA-responsive glomeruli and compare their response profiles to AAs with those of ORNs obtained in our previous study. A large number of past studies have focused either on odorant responses in the OE or on odorant-induced responses in the OB. However, a thorough comparison of odorant-induced responses of both stages, ORNs and glomeruli of the same species is as yet lacking. The glomerular response profiles reported herein markedly differ from the previously obtained response profiles of ORNs in that glomeruli clearly have narrower selectivity profiles than ORNs. We discuss possible explanations for the different selectivity profiles of glomeruli and ORNs in the context of the development of the olfactory map.

Physiology and antennal lobe projections of olfactory receptor neurons from sexually isomorphic sensilla on male Heliothis virescens

The neurophysiology and antennal lobe projections of olfactory receptor neurons (ORNs) within sexually isomorphic short trichoid sensilla of male Heliothis virescens (Noctuidae: Lepidoptera) were investigated using cut-sensillum recording and cobalt-lysine staining. A total of 202 sensilla were sorted into 14 possible sensillar categories based on odor responses and physiology of ORNs within. Seventy-two percent of the sensilla identified contained ORNs stimulated by conspecific odors. In addition, a large number of ORNs were specifically sensitive to ss-caryophyllene, a plant-derived volatile (N = 41). Axons originating from ORNs associated with individual sensilla were stained with cobalt lysine (N = 67) and traced to individual glomeruli in the antennal lobe. ORNs with responses to female sex pheromone components exhibited similar axonal projections as those previously described from ORNs in long sensilla trichodea in male H. virescens. Antennal lobe axonal arborizations of ORNs sensitive to hairpencil components were also located in glomeruli near the base of the antennal nerve, whilst those sensitive to plant odorants projected to more medial glomeruli. Comparisons with ORNs described from female H. virescens supports the notion that glomeruli at the base of the antennal nerve are associated with conspecific and interspecific odorants, whereas those located medially are associated with plant volatiles.

β‐secretase expression in normal and functionally deprived rat olfactory bulbs: Inverse correlation with oxidative metabolic activity

Cerebral hypometabolism, mitochondrial dysfunction, and beta-amyloid peptide (Abeta) accumulation are well-characterized manifestations of Alzheimer's disease (AD). beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up-regulated in sporadic AD. To explore a potential in vivo mechanism by which Abeta production is modulated by neuronal activity and/or oxidative metabolism, we compared BACE expression with cytochrome c oxidase (CO) or succinic dehydrogenase (SDH) activity in normal and functionally deprived adult rat olfactory bulb. In normal bulb, BACE was expressed predominantly in the glomerular layer, but labeling intensity within individual glomeruli varied substantially. A strong negative correlation existed between BACE labeling intensity and CO or SDH activity among individual glomeruli. Unilateral naris occlusion resulted in elevated glomerular BACE labeling in the deprived bulbs relative to the nondeprived counterparts, which was correlated with decreased CO activity in the same anatomic location. Enhanced BACE labeling was confirmed by measurements of elevated protein levels, enzymatic activity, and beta-site cleavage products of amyloid precursor protein in bulb extracts. Our findings reveal a negative regulation of BACE expression by physiological neuronal activity and an intrinsic inverse correlation between BACE expression and oxidative metabolism at the first synapse on the olfactory pathway. The results point to a biological role of BACE in synapse function and plasticity as well as a potential mechanism whereby reduced neuronal activity or metabolism could lead to amyloid overproduction in synaptic terminals.