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PubMed1995

Coculture of the vomeronasal organ and olfactory bulb of the fetal rat.

The vomeronasal organ and the olfactory bulb of the rat were cocultured from 15-day embryo siblings on collagen-coated membrane in Dulbecco's modified Eagle's medium containing fetal calf serum, horse serum, and antibiotics. At 4 days in vitro (DIV), vomeronasal axons forming two to three large fascicles were seen originating from the explants of the vomeronasal organ. Differential axonal growth was observed. Some fascicles made connections with the explants of the olfactory bulb. Twenty percent of the cocultures studied here showed the formation of connections. At 6-10 DIV many fascicles that did not connect with the olfactory bulb had degenerated, and large fascicles that were connected with the olfactory bulb survived for more than 10 DIV. The formation of connections between the vomeronasal organ and the olfactory bulb in coculture favors the survival of large nerve fascicles, but it could not be determined whether or not the presence of the olfactory bulb affects the initial orientation of the fibers and fascicles from the explants of the vomeronasal organ.

Animals↗
PubMed1993

Microglia and the developing olfactory bulb.

The developmental appearance of microglia in the rat olfactory bulb was investigated through the use of selective staining with the B4-isolectin from Griffonia simplicifolia. No changes in the density or distribution of either the spherical, macrophage "ameboid" form or the highly arborized "ramified" variety of microglia were observed in the superficial layers of the bulb between postnatal days 10 and 30. The subependymal zone exhibited the only substantial population of ameboid cells and the only developmental increases in ramified cell density during this time-period. External single naris closure, which enhances cell death in the ipsilateral bulb, did not affect microglia density, presumably due to the unusually high numbers of microglia normally present in the bulb. The olfactory bulb has a dense and relatively uniform population of microglial cells from very early stages of postnatal life, perhaps because of the constant turnover of cells and processes.

Aging↗
PubMed2000

Oxytocin induces preservation of social recognition in male rats by activating alpha-adrenoceptors of the olfactory bulb.

In this report, a series of four experiments was performed to evaluate the relationship between the olfactory bulb norepinephrine system and intra-olfactory bulb infusion of oxytocin in the preservation of social memory responses. The present data indicate that oxytocin exerts this preservation of social recognition through a specific, receptor-mediated mechanism within the olfactory bulb (experiment 1). The involvement of the olfactory bulb norepinephrine system is revealed by the demonstration that retrodialysis of oxytocin into the olfactory bulb increases norepinephrine release (experiment 4). Our data suggest that the increased output of olfactory bulb norepinephrine resulting from oxytocin appears to activate alpha-adrenoceptors to produce this preservation in recognition because infusions of clonidine into the olfactory bulb preserve recognition responses in a manner similar to that observed with oxytocin (experiment 2). In addition, a co-infusion of oxytocin with phentolamine abolishes recognition responses (experiment 3). Accordingly, this model affords the opportunity to study neuropeptide-catecholamine interactions, link these interactions with a specific behavioural outcome and identify a novel function/site of action for oxytocin in the male.

Adrenergic alpha-Agonists↗
PubMed1986

Mitral cell differentiation and synaptogenesis of rat presumptive olfactory bulb in organ culture.

The ultrastructure of differentiating rat presumptive olfactory bulb in organ culture was investigated with particular reference to mitral cell differentiation and formation of synapses. The presumptive olfactory bulb and olfactory mucosa were dissected en bloc from rat embryos on the fifteenth day of gestation and cultured for 7 days, after which the explants were examined by electron microscopy. The presumptive olfactory bulb had differentiated into a laminated structure with layers corresponding to the glomerular, external plexiform and mitral cell layers. Mitral-like cells were identified by their location and large cell size. Ultrastructural observations indicated that they were relatively well-differentiated. Their dendrites extended into the glomerular layer in which they were postsynaptic to incoming olfactory axons. The distal part of these dendrites frequently contained coated vesicles. Both asymmetrical and symmetrical synapses were found. The symmetrical synapses involved dendrodendritic contacts between periglomerular cells. Synapses in reciprocal arrangements were not observed in the organ cultures.

Animals↗
PubMed1988

Real-time imaging of evoked activity in local circuits of the salamander olfactory bulb.

The encoding of olfactory information in the central nervous system (CNS) depends on spatially distributed patterns of activity generated simultaneously in many neuronal circuits. Optical neurophysiological recording permits analysis of neural activity non-invasively and with high spatial and temporal resolution. Here, a video method for imaging voltage-sensitive dye fluorescence in vivo is used to map neuronal activity in local circuits of the salamander olfactory bulb. The method permits the imaging of simultaneous ensemble transmembrane activity in real time. After electrical stimulation of the olfactory nerve, activity spreads centripetally from the sites of synaptic input to generate nonhomogeneous response patterns that are presumably mediated by local circuits within the bulbar layers. The results also show the overlapping temporal sequences of activation of cell groups in each layer. The method thus provides high resolution, sequential video images of the spatial and temporal progression of transmembrane events in neuronal circuits after afferent stimulation and offers the opportunity for studying ensemble events in other brain regions.

Animals↗
PubMed2001

Developmental changes in PSD-95 and Narp mRNAs in the rat olfactory bulb.

Glutamate is the main neurotransmitter in the olfactory bulb. Recently, postsynaptic-density 95 (PSD-95) and neuronal activity-regulated pentraxin (Narp) have been reported to be pivotal for targeting and clustering of NMDA receptors and AMPA receptors, respectively. We thus investigated the expressions of PSD-95 and Narp mRNAs in the rat developing olfactory bulb. PSD-95 mRNA was already expressed in most neurons on the first postnatal day (P1). On the other hand, Narp mRNA expression was weakly seen only in mitral cells on P1. Thereafter, we found initial expression of Narp mRNA on P7 in periglomerular cells, and on P14 in granular cells, indicating that in the developing olfactory bulb PSD-95 mRNA expression precedes Narp mRNA expression, and that the expression pattern of Narp mRNA seems to be well correlated with the maturation of the neurons. These results indicate that PSD-95 and Narp play important roles in making efficient excitatory synapses in the developing rat olfactory bulb, and suggest that olfactory neurons might first express PSD-95 for making efficient NMDA receptors and thereafter express Narp for efficient AMPA receptors.

Animals↗
PubMed1998

Olfactory bulb development is altered in small-eye (Sey) mice.

Small-eye (Sey) is a spontaneous, semidominant murine mutation that results from a point mutation in the Pax-6 gene. Both the eyes and the olfactory system fail to develop in homozygotes and these animals die neonatally. Heterozygotes (Sey/+) have different degrees of eye abnormalities including decreased lens size and cataracts. In the present study, we examined whether one mutated allele of Pax-6 also affects olfactory system development. By 42 days of age, main olfactory bulb volume was significantly decreased in Sey/+ animals compared with wild-type littermates, and this effect was even more dramatic in 70-day-old animals. In contrast, there was no effect on accessory olfactory bulb, olfactory epithelial, or vomeronasal organ development at any age in Sey/+ animals, demonstrating the specificity of the effect. In the main olfactory bulb, the largest differences in laminar volume were found in the glomerular and granule cell layers. These layers contain the olfactory bulb interneurons, and a subpopulation of these cells were found to be Pax-6 immunoreactive. Examination of the neurochemical consequences of this mutation showed that the number of both tyrosine hydroxylase (TH)- and gamma-aminobutyric acid (GABA)-immunoreactive profiles were dramatically decreased in Sey/+ animals as compared with controls. In contrast, neither calretinin nor calbindin immunoreactivity was affected by this mutation. Dual-labeling immunohistochemistry showed that nearly all TH-immunoreactive cells and a subpopulation of GABA-immunoreactive cells coexpressed Pax-6. However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive. These data indicate that two normal alleles of Pax-6 are required for normal olfactory bulb development and, as part of this effect, this gene may be involved in the development of specific neurotransmitter systems.

Aging↗
PubMed1980

Castration decreases olfactory bulb norepinephrine in male rats but not hamsters.

Norepinephrine (NE) concentrations were measured in the olfactory bulbs and olfactory cortex of male albino rats and golden hamsters sacrificed 13-16 days after castration or sham surgery. Castration significantly decreased NE concentrations in the olfactory bulbs of rats but not hamsters. Castration had no significant influence on NE levels in the olfactory cortex of either species. Regional brain weights were not influenced by surgery, and previous olfactory exposure had no significant effect on any variable measured. The decrease in rat olfactory bulb NE levels may be involved in castration-induced changes in preferences for conspecific odors.

Animals↗
PubMed1999

Transregulation of erbB expression in the mouse olfactory bulb.

Previously, we have shown that erbB-3 expression is restricted to the ensheathing cells of the olfactory nerve layer, while erbB-4 is found in the periglomerular and mitral/tufted cells of the olfactory bulb and in cells coming out from the rostral migratory stream of the subependymal layer. In the present work, we have treated adult mice with zinc sulfate intranasal irrigation and analyzed erbB-3 and erbB-4 expression in the deafferented olfactory bulb. Following treatment, olfactory axons undergo degeneration, as indicated by the loss of OMP expression in the deafferented olfactory bulb. The thickness of the olfactory nerve layer is reduced, but the specific intensity of erbB-3 labeling in the remaining olfactory nerve layer is increased with respect to control. Interestingly, following deafferentation, erbB-4 immunoreactivity decreases specifically in cell types that normally make synaptic contacts with primary olfactory neurons in the glomeruli, i.e. periglomerular and mitral/tufted cells. Partial lesion of the olfactory epithelium allows regenerative axon growth of olfactory neurons to the olfactory bulb. Following olfactory axon regeneration, erbB-3 and erbB-4 immunoreactivity in the olfactory bulb is similar to control. Thus, like tyrosine hydroxylase, the down regulation of erbB-4 expression in the periglomerular cells is reversible.

Administration, Intranasal↗
PubMed1989

Impairment of olfactory memory by local infusions of non-selective excitatory amino acid receptor antagonists into the accessory olfactory bulb.

Female mice form a long-term olfactory memory to the pheromones of the male that mates with them. This memory is dependent on neural mechanisms within the accessory olfactory bulb. In this study we show that localized infusions of the excitatory amino acid receptor blocker, gamma-D-glutamylglycine, into the accessory olfactory bulb prevents memory formation. This is in marked contrast to the effects of infusions of the specific N-methyl-D-aspartate receptor antagonists, D-2-amino-5-phosphonovaleric acid and MK 801, which are without effect on memory formation. Excitatory amino acid receptor blockade by localized infusion of these drugs into the accessory olfactory bulb induced seizures. This paradoxical effect could only be due to disinhibition of granule cell GABAergic inhibitory feedback to the mitral cell. This was confirmed by the pregnancy blocking effect of these drugs, an event which also occurs with bicuculline infusions into the accessory olfactory bulb. These findings strongly implicate excitatory amino acid receptors in memory formation to the pheromones of the mating male and localize the mechanism to the reciprocal dendro-dendritic synapse between mitral and granule cells.

Animals↗
PubMed2003

Wiring the olfactory bulb--activity-dependent models of axonal targeting in the developing olfactory pathway.

Two recent experimental studies /20,21/ revealed that odorant-evoked activity-dependent competition is significant in the organisation and maintenance of the olfactory system. In this paper, we investigate the generation of a chemotopic sensory map in the olfactory bulb through three models driven by high-density optical chemosensor arrays which have similar properties to olfactory receptor neurons. By exposing the sensor arrays to various odours, these models were subjected to Hebbian learning to achieve self-organisation, potentially explaining the activity-dependent competition demonstrated by these recent studies. Our final model also predicts a role for periglomerular cells in the formation of the chemotopic sensory map in the olfactory bulb.

Animals↗
PubMed2003

Inverse expression of olfactory cell adhesion molecule in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat main olfactory bulb.

The projection of olfactory sensory neuron (OSN) axons from the olfactory epithelium (OE) to the olfactory bulb (OB) is highly organized but topographically complex. Evidence suggests that odorant receptor expression zones in the OE map to the OB about orthogonal axes. One candidate molecule for the formation of zone-specific targeting of OSN axon synapses onto the OB is the olfactory cell adhesion molecule (OCAM). OCAM(+) OSNs are restricted to three of the four zones in the OE and project their axons to the ventral OB where they form synapses with mitral/tufted (M/T) cells. To determine when this zonal connection is established, we have examined OCAM expression in rat olfactory system, during seminal periods of glomerular formation. OCAM(+) axons sort out in the ventral olfactory nerve layer of the OB before glomerular formation. Surprisingly, OCAM was also expressed transiently by subsets of M/T cell dendrites located in the dorsal OB. The expression of OCAM by OSN axons and M/T dendrites was asymmetrical; in the dorsal OB, OCAM(-) OSN axons synapsed on OCAM(+) M/T dendrites, whereas in the ventral OB, OCAM(+) OSN axons synapsed on OCAM(-) M/T dendrites. The restricted spatial map of OCAM(+) M/T cells appeared earlier in development than the zonal segregation of OCAM(+) OSN axons. Thus, OCAM on M/T cell dendrites may act in a spatiotemporal window to specify regions of the developing rat OB, thereby establishing a foundation for mapping of the OE zonal organization onto the OB.

Animals↗
PubMed2001

Negatively calcium-modulated membrane guanylate cyclase signaling system in the rat olfactory bulb.

The mechanism by which the individual odor signals are translated into the perception of smell in the brain is unknown. The signal processing occurs in the olfactory system which has three major components: olfactory neuroepithelium, olfactory bulb, and olfactory cortex. The neuroepithelial layer is composed of ciliated sensory neurons interspersed among supportive cells. The sensory neurons are the sites of odor transduction, a process that converts the odor signal into an electrical signal. The electrical signal is subsequently received by the neurons of the olfactory bulb, which process the signal and then relay it to the olfactory cortex in the brain. Apart from information about certain biochemical steps of odor transduction, there is almost no knowledge about the means by which the olfactory bulb and cortical neurons process this information. Through biochemical, functional, and immunohistochemical approaches, this study shows the presence of a Ca(2+)-modulated membrane guanylate cyclase (mGC) transduction system in the bulb portion of the olfactory system. The mGC is ROS-GC1. This is coexpressed with its specific modulator, guanylate cyclase activating protein type 1 (GCAP1), in the mitral cells. Thus, a new facet of the Ca(2+)-modulated GCAP1--ROS-GC1 signaling system, which, until now, was believed to be unique to phototransduction, has been revealed. The findings suggest a novel role for this system in the polarization and depolarization phenomena of mitral cells and also contradict the existing belief that no mGC besides GC-D exists in the olfactory neurons.

Animals↗
PubMed1995

Electrophysiological responses of single olfactory bulb neurons to amino acids in the channel catfish, Ictalurus punctatus.

1. Responses of 89 single olfactory bulb neurons from 43 channel catfish, Ictalurus punctatus, to amino acid odorants were recorded in vivo simultaneously with the electro-olfactogram (EOG). Recording time for individual neurons ranged from 16 to 344 min. The averaged spontaneous frequency ranged from < 1 to 16 action potentials/s with a mean frequency of 5.2 +/- 3.6 (SD) action potentials/s. 2. Histological examinations of carbocyanine dye 1,1'diocadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled olfactory bulbs and electrical stimulation of the olfactory tracts in a subset of experiments suggested that the majority of the recorded olfactory bulb neurons in this study were mitral cells. 3. Olfactory bulb neurons responded to amino acids with either an excitation or suppression of the background neural activity. Of the 337 stimulus applications, 28% of the responses were excitatory, and 33% were suppressive. The approximately 1:1 ratio of excitatory to suppressive responses for all stimulus applications suggests that suppressive responses also play important roles in the coding of odorant information in the channel catfish. 4. Responses of single olfactory bulb neurons were highly reproducible over time (up to 5 h). Responses to any amino acid never changed from excitation to suppression, or vice versa over time. 5. Single olfactory bulb neurons responded with excitation or suppression to more than one amino acid previously indicated to bind to independent receptors. 6. Estimated threshold concentrations for activation of an olfactory bulb neuron ranged from 10(-7) to 10(-3) M and were different from neuron to neuron for a particular stimulus and from stimulus to stimulus for a particular neuron. Responses of single olfactory bulb neurons to a given amino acid did not change from excitation to suppression, or vice versa, across different suprathreshold concentrations.

Amino Acids↗
PubMed1996

Synaptic degeneration and remodelling after fast kindling of the olfactory bulb.

Kindling of the olfactory bulb using a novel fast protocol (within 24 h) was studied in rats. In target brain regions, the effects of kindling were measured on the concentration of glial fibrillary acidic protein (GFAP) by dot-blot and on the concentrations of neural cell adhesion molecule (NCAM) and the 25 kDa synaptosomal associated protein of the D3 immunoprecipitate (D3(SNAP-25)) by crossed immunoelectrophoresis. Bilateral increases in the levels of GFAP, indicating activation of astrocytes, were detected in primary olfactory cortical projection areas, including the piriform cortex, and also in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling. At this time, however, an overall pattern of ipsilateral decreases in the synaptic marker proteins NCAM and D3(SNAP-25) indicated that this remodelling occurred on a background of synaptic degeneration. These results confirm previous studies showing that kindling is associated with synaptic remodelling and neuronal degeneration in the hippocampal formation and extends the area of plasticity to include the piriform cortex which is believed to be central to the kindling process.

Animals↗
PubMedDate not supplied

Response of the olfactory bulb antioxidant system following diethyldithiocarbamate (DDTC) administration in rats.

This study was designed in order to evaluate alterations in the reactive oxygen species (ROS) scavenging system in olfactory bulb, dorsal neocortex and cerebellum for 6 weeks following a single subcutaneous dose (600 mg kg-1) of diethyldithiocarbamate (DDTC) to rats. A single dose of DDTC caused substantial damage to the olfactory epithelium and degeneration within the olfactory bulb. The epithelium regenerates, followed by regeneration in the olfactory bulb. The mean olfactory bulb weight decreased significantly 3 days after DDTC administration and gradually recovered to control values in 6 weeks. The DDTC-induced lesion of the olfactory nerve resulted in significant changes in glutathione (GSH) and antioxidant enzyme activities in olfactory bulb. In contrast, no significant changes were found in either cerebellum or dorsal neocortex. These observations indicate that a single dose of DDTC selectively affected the ROS scavenging system of the olfactory bulb. Moreover, these changes persisted for at least 6 weeks, which includes regeneration and synaptogenesis. Olfactory bulb GSH concentrations decreased significantly by 47 +/- 4%, glutathione reductase activity decreased by 18 +/- 3% and catalase activity increased by 27 +/- 7% over the 6 weeks. Superoxide dismutase activity decreased significantly in olfactory bulb of rats by 32 +/- 6% at 3 days following the lesion and then recovered and increased by 38 +/- 3% at 3 weeks. Olfactory bulb malondialdehyde concentrations were elevated (298 +/- 67%) throughout the post-lesion survival period, although this change did not reach the stringent statistical significance level required in this study. These data suggest that increased ROS flux perturbs the olfactory bulb antioxidant defense system during olfactory nerve regeneration.

Animals↗
PubMed1990

The effect of acetylcholine on rat olfactory bulb unit activity.

The olfactory bulb (OB) of the rat receives an extrinsic innervation from the most anterior part of the basal forebrain cholinergic complex. The effect of microiontophoretically applied acetylcholine (ACh) on OB unit activity was studied in 16 adult male rats. A total of 80 units was recorded and in 50% of the cases the cell layer where the recording was done was clearly identified. The results provide evidence for a particularly high level of sensitivity to ACh in the outer glomerular layer (73%). Both inhibitory and excitatory responses were found. These results are in agreement with histological studies indicating that this layer presents the highest density of cholinergic terminals. As a whole, present knowledge suggests the existence of a strong cholinergic control of the olfactory input at the level of the first synapse in the system.

Acetylcholine↗