The spatial distribution of odour induced potentials in the olfactory bulb of char and trout (Salmonidae)

Monopolar DC-recordings were made of the gross responses from the olfactory bulb of char (Salvelinus alpinus syn. Salmo alpinus L.) and trout (Salmo trutta L.) during stimulation with different odours. The response features studied were: the magnitude and polarity of the slow potential shift, the amplitude of the induced waves and their asymmetrical waveform. Amino acids elicited the largest responses in the lateral part of the bulb. Water containing “crude fish odour” caused the largest responses in the rostral and medial parts. The results demonstrate odour specific differences in the localization of the bulb responses and the separate origin of the slow potential and the induced waves.     

Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression

The purpose of this study was to assess olfactory function and olfactory bulb volume in patients with acute major depression in comparison to a normal population. Twenty-one patients diagnosed with acute major depressive disorder and 21 healthy controls matched by age, sex and smoking behavior participated in this study. Olfactory function was assessed in a lateralized fashion using measures of odor threshold, discrimination and identification. Olfactory bulb volumes were calculated by manual segmentation of acquired T2-weighted coronal slices according to a standardized protocol. Patients with acute major depressive disorder showed significantly lower olfactory sensitivity and smaller olfactory bulb volumes. Additionally, a significant negative correlation between olfactory bulb volume and depression scores was detected. Their results provide the first evidence, to our knowledge, of decreased olfactory bulb volume in patients with acute major depression. These results might be related to reduced neurogenesis in major depression that could be reflected also at the level of the olfactory bulb.     

Somatostatin-14-like immunoreactive neurons and fibres in the human olfactory bulb

Summary This study describes the morphological features and the distribution pattern of neurons in the human olfactory bulb which are immunoreactive for an antiserum against the neuropeptide somatostatin-14.Immunoreactive nerve cell bodies were mainly found in the white matter surrounding the cell clusters of the anterior olfactory nucleus. Some immunoreactive neurons were also found scattered throughout the anterior olfactory nucleus and the deeper parts of the inner granule cell layer. Only a few immunoreactive neurons were localized in the glomerular layer and the outer granule cell layer.Immunoreactive fibres were found in all layers of the olfactory bulb. In addition, an impressive number of coiled and kinked immunoreactive fibres were localized within the anterior olfactory nucleus forming a dense plexus. Accumulations of twisted and coiled branches of immunoreactive fibres were rarely found either surrounding or within the olfactory glomerula.The characteristics of somatostatin-14 immunoreactive neurons as seen in the combined pigment-Nissl preparation were studied after decolourizing the chromogen and restaining the preparations with aldehydefuchsin in order to demonstrate the lipofuscin pigment and gallocyanin chrome alum for Nissl material. About 90% of the immunoreactive neurons studied in this manner turned out to be devoid of lipofuscin granules. The remaining 10% displayed different patterns of pigmentation.These findings suggest the presence of different types of somatostatin-14-like immunoreactive neurons in the olfactory bulb of the human adult.     

Immunohistochemical and enzyme-histochemical study on the accessory olfactory bulb of the dog

The accessory olfactory bulb (AOB) is a primary center of the vomeronasal system. In the dog, the position and morphology of the AOB remained vague for a long time. Recently, the morphological characteristics of the dog AOB were demonstrated by means of lectin-histochemical, histological, and immunohistochemical staining, although the distribution of each kind of neuron, especially granule cells, remains controversial in the dog AOB. In the present study, we examined the distribution of neuronal elements in the dog AOB by means of immunohistochemical and enzyme-histochemical staining. Horizontal paraffin or frozen sections of the dog AOB were immunostained with antisera against protein gene product 9.5 (PGP 9.5), brain nitric oxide synthase (NOS), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), substance P (SP), and vasoactive intestinal polypeptide (VIP) by avidin-biotin peroxidase complex method. In addition, frozen sections were stained enzyme-histochemically for NADPH-diaphorase. In the dog AOB, vomeronasal nerve fibers, glomeruli, and mitral/ tufted cells were PGP 9.5-immunopositive. Mitral/ tufted cells were observed in the glomerular layer (GL) and the neuronal cell layer (NCL). In the NCL, a small number of NOS-, GAD-, and SP-immunopositive and NADPH-diaphorase positive granule cells were observed. In the GL, GAD-, TH-, and VIP-immunopositive periglomerular cells were observed. In the GL and the NCL, TH-, and VIP-immunopositive short axon cells were also observed. In addition to these neurons, TH- and SP-immunopositive afferent fibers were observed in the GL and the NCL. We could distinctly demonstrate the distribution of neuronal elements in the dog AOB. Since only a small number of granule cells were present in the dog AOB, the dog AOB did not display such a well-developed GCL as observed in the other mammals. Anat. Rec. 252:393–402, 1998. © 1998 Wiley-Liss, Inc.     

Patterns of expression of the immediate-early gene egr-1 in the accessory olfactory bulb of female mice exposed to pheromonal constituents of male urine

Male mice excrete large quantities of major urinary proteins that have been proposed to have an important pheromonal role either alone or by way of their bound ligands. We have found that these major urinary proteins are not only likely to mediate the pregnancy blocking effects of male urine, but that they also convey the strain recognition signal of the male pheromone. Recent molecular biological investigations have characterized two classes of pheromonal receptor in the vomeronasal organ that appear to project separately to anterior and posterior regions of the accessory olfactory bulb. However, it is not known whether these separate pathways handle fundamentally different types of pheromonal information. We have attempted to investigate this question using the expression of the immediate-early gene egr-1 as a marker for activity of neurons in the accessory olfactory bulb of female mice in response to putative pheromonal constituents. Exposure to 2,3 dihydro-exo-brevicomin and 2-sec-butyl-4,5-dihydro-thiazole, the main ligands bound to the major urinary proteins, elicited expression of egr-1 in clusters of presumed mitral neurons at the medial and lateral margins of the posterior accessory olfactory bulb. Whole male urine and a preparation of major urinary proteins that had been stripped of their ligands induced egr-1 expression in mitral cells of the anterior half of the accessory olfactory bulb in addition to the posterior clusters.

This would suggest that the anterior and posterior halves of the accessory olfactory bulb are processing different aspects of the male pheromone signal with the anterior region, which responds preferentially to major urinary proteins, being principally concerned with the strain recognition component.     

An experimental study of the projection of the amygdala to the accessory olfactory bulb and its relationship to the concept of a dual olfactory system

Summary The present anatomical findings point to the existence of a separate subdivision of the olfactory system whose connections are quite different from the principal part. The main olfactory bulb has olfactory afferents from the receptors of the general olfactory mucosa, while the accessory bulb has afferents from receptors in the vomeronasal organ. The main bulb projects to the olfactory tubercle and pyriform cortex, while the accessory bulb projects to the amygdala. In turn these areas are further related with the medial forebrain bundle in the case of the pyriform cortex and olfactory tubercle, and with the medial preoptic area and medial hypothalamus in the case of the amygdala. The main and accessory olfactory bulbs are further distinguished by their centrifugal connections, the main bulb receiving fibres from the olfactory tubercle passing through the lateral olfactory tract, and the accessory olfactory bulb receiving fibres from the amygdala through the stria terminalis. The centrifugals to the accessory olfactory bulb resemble those to the main bulb in that both appear to terminate upon granule cells, although further projections to the external plexiform layer or to the periglomerular region have not been demonstrated for the accessory bulb. By virtue of its neural connections the accessory olfactory system is ideally placed to mediate the effects of olfactory stimuli on reproduction.     

Odorant modulation of neuronal activity and local field potential in sensory-deprived olfactory bulb

Neuronal discharge and local field potential (LFP) oscillations in the olfactory bulb (OB) are modulated by odorant stimulation. The LFP oscillations have been proposed as the mechanism that facilitates synchronization of OB output neurons and the representation of similar odorants. Gamma LFP oscillations depend on the OB inhibitory network and early sensory deprivation modifies this inhibitory network. However, little is known about the LFP oscillations and neuronal discharge in the deprived OB. We examined the mitral/tufted (MT) cells' oscillatory activity and LFP oscillations in both sensory-deprived and normal OBs in urethane anesthetized rats. We found that MT cells in deprived and normal OBs have similar basal mean firing rate; 44% of the recorded cells in deprived OB and only 8% of the cells in normal OB showed firing rate modulation by odorants, both exhibiting a similar ratio of excitatory to inhibitory responses. A fraction of MT cells exhibited oscillatory discharge centered on gamma (60–70 Hz) and beta (20 Hz) frequencies, although this feature was not consistently dependent on odorant stimulation. Odorants decreased the LFP oscillatory power in the gamma band (35–90 Hz) and increased the power in the beta band (12–30 Hz). The modulation of LFP oscillations by odorants was also predominant in the deprived (53%) compared to the normal OB (17%). In contrast, a higher fraction of MT cells' discharge was locked to the gamma LFP cycle in the normal OB. These results suggest that early unilateral olfactory deprivation increases the OB sensitivity to odorants and reduce the temporal synchrony between unitary activity and gamma LFP oscillations without altering the basal neuronal discharge.     

Estrogen-induced region specific decrease in the density of 5-bromo-2-deoxyuridine-labeled cells in the olfactory bulb of adult female rats

Effects of chronic estrogen treatment on the survival rate of newly integrated interneurons were studied in the olfactory bulb of adult (250-300 g) female rats. Ovariectomized rats received 17-beta estradiol dissolved in sesame oil (i.p., 100 microg/100 g body weight [b.w.]) during six consecutive days, and on day 6 they were also injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU, i.p., 50 mg/kg b.w.) in every 2 hours during 8 hours. After 21 days of survival animals were killed and the density of BrdU-immunoreactive cells was analyzed in the granule cell and glomerular layer both in the main and accessory olfactory bulb. A significant decrease was found in the density of BrdU-labeled cells in both layers examined in the accessory olfactory bulb of ovariectomized and estradiol-treated rats when compared with those of ovariectomized and vehicle-treated animals. In the main olfactory bulb, in contrast, no difference was observed in the density of BrdU-immunoreactive cells in either of the two layers. Our results suggest that cells destined to the glomerular and granule cell layers react in the same way to chronic estrogen treatment, and the effect of estradiol is region specific, at least, within the olfactory bulb. 17-Beta estradiol reduces the density of newly generated cells in the accessory olfactory bulb, an area involved in the perception of pheromones, thus having a role in regulating sexual behavior, while the rate of integration and survival of newly born cells in the first relay station of the main olfactory pathway, i.e. the main olfactory bulb, remains unchanged.     

Olfactory bulb ventricles as a frequent finding in magnetic resonance imaging studies of the olfactory system

Background. In some species an embryologic cavity inside the olfactory bulb (OB) persists and is called olfactory bulb ventricle (OBV). It is generally assumed that OBVs in humans are solitary findings representing remnants of embryologic structures that were not fully regressed, although the incidence of OBVs was never examined. Using magnetic resonance imaging (MRI), the present study aimed to study the incidence of OBVs in healthy human subjects. Material and methods. A total of 122 individuals participated. Volumes of the right and left OB were determined using MRI scans and a standardized protocol for OB analysis. For comparison, OBs of 42 cadavers were collected and sectioned. Results. The main finding of this study was the high incidence of OBV-like structures in our study group. Seventy-two out of 122 (59%) participants yielded signs for an OBV whereas three out of 42 postmortem OBs contained histologically detectable OBV. Discussion: This stands in disagreement with the previous assumption of complete obliteration at the time of birth. This discrepancy may be explained by the fact that our present findings are based on modern MRI techniques with much higher resolution than 10 or 20 years ago. Another possible explanation for the discrepancy between studies based on MRI and histopathology might relate to postmortem resorption of cerebrospinal fluid from OBVs. Especially with a long postmortem interval OBVs may collapse and may no longer appear as an open cavity.     

Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb

When female mice are mated, they form a memory to the pheromonal signal of their male partner. Several lines of evidence indicate that the neural changes underlying this memory occur in the accessory olfactory bulb (AOB) at the first stage of the vomeronasal system. The formation of this memory depends on the mating-induced release of noradrenaline in the AOB. In addition to noradrenaline, the neuropeptide oxytocin (OT) is also released within the central nervous system during mating. Because OT has been implicated in social memory and its receptors are expressed in the AOB, we hypothesized that OT might promote the strength of synaptic transmission from mitral to granule cells in the AOB. To test this hypothesis, we analyzed the lateral olfactory tract-evoked field potential that represents the granule cell response to mitral cell activation and its plasticity in parasagittal slices of the AOB. Of the 10-, 20-, 50-, and 100-Hz stimulations tested, the 100-Hz stimulation was optimal for inducing long-term potentiation (LTP). OT paired with 100-Hz stimulation that only produced short-term potentiation enhanced LTP induction in a dose-dependent manner. OT-paired LTP was blocked by both the selective OT antagonist desGly-NH₂,d(CH₂)₅[Tyr(Me)²,Thr⁴]-ornithine vasotocin and the N-methyl-d-aspartate (NMDA) receptor antagonist dl-2-amino-5-phosphonovaleric acid. These results indicate that OT can function as a gate to modulate the establishment of NMDA receptor-dependent LTP at the mitral-to-granule cell synapse in the AOB.     

Proteinase-activated receptors 1 and 2 in rat olfactory system: layer-specific regulation of multiple signaling pathways in the main olfactory bulb and induction of neurite retraction in olfactory sensory neurons

Proteinase-activated receptors (PARs) are a family of four G protein-coupled receptors that are widely distributed in the CNS and involved in neural cell proliferation, differentiation and survival. The olfactory system undergoes continuous neurogenesis throughout life and may represent a critical target of PAR cellular actions. In the present study we investigated the functional activity of PAR1 and PAR2 in microdissected tissue preparations of olfactory nerve-glomerular layer (ON-GL), external plexiform layer (EPL) and granule cell layer (GRL) of the rat main olfactory bulb and in primary cultures of olfactory neuroepithelial cells. Activation of either PAR1 or PAR2 regulated multiple signaling pathways, including activation of pertussis-toxin sensitive Gi/o proteins, inhibition of cyclic AMP formation, stimulation of Gq/11-mediated phosphoinositide (PI) hydrolysis, phosphorylation of Ca2+/calmodulin-dependent protein kinase II and activation of the monomeric G protein Rho, predominantly in ON-GL, whereas only activation of Rho was detected in the deeper layers. Olfactory nerve lesion by nasal irrigation with ZnSO4 induced a marked decrease of PAR signaling in ON-GL. In primary cultures of olfactory neurons, double immunofluorescence analysis showed the localization of PAR1 and PAR2 in cells positive for olfactory-marker protein and neuron-specific enolase. Cell exposure to either nanomolar concentrations of thrombin and trypsin or PAR-activating peptides caused rapid neurite retraction. This study provides the first characterization of the laminar distribution of PAR1 and PAR2 signaling in rat olfactory bulb, demonstrates the presence of the receptors in olfactory sensory neurons and suggests a role of PARs in olfactory sensory neuron neuritogenesis.     

Expanding the clinical and neuroradiological phenotype of 6q27 microdeletion: olfactory bulb aplasia and anosmia

Subtelomeric deletions of chromosome 6q may result in a syndrome with brain malformations, comprising hydrocephalus and hypoplasia of the corpus callosum. Aplasia of the olfactory bulbs (OB) or anosmia has not been described in this syndrome. We describe a 3-year-old girl and a 25-year-old man with subtelomere 6q deletions. Both patients had aplastic OB and hydrocephalus. Subtelomeric 6q deletions might be underdiagnosed as anosmia can be the only symptom.     

Olfactory bulb networks revealed by lateral olfactory tract stimulation in the in vitro isolated guinea-pig brain

Olfactory information processing is mediated by synaptic connections between the olfactory bulbs (OBs) and piriform-limbic cortices. Limited accessibility using common in vivo and in vitro preparations has hindered previous attempts to define these synaptic interactions. We utilized the isolated guinea-pig brain preparation to overcome these experimental limitations. Previous studies demonstrated extensive functional preservation in this preparation maintained in vitro by arterial perfusion. Field potential laminar profiles were performed with multi-channel probes in the OB following stimulation of both the lateral olfactory tract (LOT) and the anterior piriform cortex (APC). Current-source density analysis was carried out on laminar profiles to reconstruct current sinks/sources associated with intrinsic synaptic activities. LOT stimulation induced sequentially i) an antidromic population spike (at 2.66+/-0.39 ms) located in the mitral cell layer that was resistant to 100 Hz high-frequency stimulation (HFS) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), ii) a component located in the external plexiform layer at 3.85+/-0.63 ms that was unaffected by HFS, iii) a large amplitude potential (peak amplitude at 5.84+/-0.58 ms) generated in the external plexiform layer, abolished by HFS and CNQX, but not by bicuculline (50 microM), iv) a late response (onset at 20.00+/-2.94 ms) abolished by CNQX and enhanced by bicuculline. Stimulation of the APC also induced a late potential abolished by HFS and CNQX. Both APC-evoked and late LOT-evoked responses were abolished by a transverse cut to separate OB from APC. These results demonstrate in an isolated mammalian brain preparation the presence of reciprocal synaptic interactions between the OB and piriform cortical structures.