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NMDA-dependent, network-driven oscillatory activity induced by bicuculline or removal of Mg2+ in rat olfactory bulb neurons.

Spontaneous, low-frequency voltage oscillations (LFOs) were observed in the neurons of rat olfactory bulb upon disinhibition with GABAA antagonists and/or removal of Mg2+ from external saline. Ordinarily, LFOs presented a highly organized temporal structure, with bursts recurring regularly at about 0.05 Hz. Slow depolarizing shifts with similar frequencies were observed in all types of bulbar neurons. Simultaneous recordings from mutually independent neurons showed that LFOs were highly synchronized in distinct cells. The occurrence of LFOs was prevented by NMDA, but not AMPA/kainate, receptor antagonists. The oscillations were also halted by Ca2+ antagonists and tetrodotoxin. The pace of the oscillations was reset by stimulation of the olfactory nerve but not by direct injection of depolarizing current into the oscillating cell. Removal of the outer portion of the slice with a cut along the external plexiform layer provided crucial evidence that the bursting activity first initiated in the glomerular region and propagated synaptically downstream towards the inner layers, suggesting an organizing role for olfactory glomeruli.

Animals↗

Intranasal trigeminal detection of chemical vapors by humans.

The majorityof 14 human observers lacking olfactory nerve function detected, by nasal inhalation, over one quarter of 31 chemicals commonly used in olfactory research. No major differences were noted between anosmic observers with and without documented anatomic, genetic, or physiologic etiology. Detected compounds differed significantly from nondetected ones on the basis of a number of chemical properties, including water solubility and molecular weight. Detection thresholds of the anosmics, established by a single staircase procedure, were approximately two log volume concentration steps above those of normals for two compounds examined. Exponents of power functions fitted to magnitude estimates of the anosmics did not differ significantly from those fitted to the estimates of matched normal controls. These data indicate the trigeminal nerve may play an important role in human nasal chemoreception and that effective trigeminal stimulants may be predictable on physicochemical grounds.

Adolescent↗

Ganglion cells of the terminal nerve: morphology and electrophysiology.

The ganglion cells of the terminal nerve (TN cells) in the carp were identified using intracellular recording and staining techniques. The TN cells showed characteristic location and morphology as well as characteristic responses after electrical shocks to the olfactory nerve and tracts. These features of the TN cells were distinct from those of the mitral or other cells in the olfactory bulb.

Animals↗

The human primary olfactory pathway: fine structural and cytochemical aspects during development and in adults.

Despite increasing knowledge about the biophysiology of the human olfactory system, understanding of the development of this pathway in humans lags considerably behind that of other vertebrates. Developmental studies have largely concentrated on the generation of cell types in the olfactory epithelium during the first trimester, while detailed ultrastructural observations usually describe the adult morphology. In this review, we have shown that contrary to what has been generally assumed, the surface of the human olfactory epithelium is heterogeneous and that its olfactory nerves differ ultrastructurally from those of other vertebrates studied. The development of the human primary olfactory pathway is discussed in terms of the appearance of olfactory bulb laminae, synaptogenesis and the expression of specific cell markers, such as the S-100 protein and olfactory marker protein (OMP). Positive immunohistochemical staining for N-cadherin in human fetuses suggests that growth of olfactory axons to their target may be mediated by cell adhesion molecules. The overall data presented here indicate that this pathway develops more precociously in humans than in rodents. Whether this translates also to earlier functional maturity remains to be elucidated.

Adult↗

LHRH neuronal subtypes have multiple origins in chickens.

Previous studies indicate that LHRH neurons of the septal-preoptic area originate in the olfactory epithelium. In the current study, we found that LHRH neurons entering the telencephalon from the olfactory nerve were not continuous with LHRH neurons in the thalamus. In addition, ablation of the olfactory placode eliminated LHRH neurons in the telencephalon but did not eliminate LHRH neurons in the thalamus. We propose that there are at least two sites of LHRH neuron production, the olfactory epithelium and the diencephalon.

Animals↗

Induction of agenesis of the corpus callosum by the destruction of anlage of the olfactory bulb using fetal laser surgery exo utero in mice.

It has long been discussed why some congenital anomalies were often involved with abnormalities in other organs, for example, brain anomalies accompanied by limb anomalies or cleft palate. The mechanism of combined abnormalities has been mysterious, and usually explained as pleiotropism. A combination between agenesis of the olfactory bulb and agenesis of the corpus callosum has been reported. In the present experiments, it has been suggested that non-attachment of the olfactory nerve to the rostro-ventral tip of the telencephalon blocked the induction of the olfactory bulbs from the telencephalon in genetic arhinencephalic mouse embryos. It was shown that the destruction of the olfactory bulb anlage using fetal laser surgery exo utero becomes a trigger of agenesis of the corpus callosum and irregular connection of the anterior commissure in later morphogenesis of the mouse brain. We believe that a fetal surgical experiment like this will make clear the morphogenetic mechanism of the combined abnormalities that have been previously explained as pleiotropism.

Abnormalities, Multiple↗

Expression of glucocorticoid receptor mRNA and protein in the olfactory mucosa: physiologic and pathophysiologic implications.

OBJECTIVES: Define the presence and distribution of glucocorticoid receptors (GRs) within the olfactory mucosa in order to assess potential physiologic and pathophysiologic effects of these hormones on olfaction. STUDY DESIGN: The olfactory mucosa was harvested from adult male rats and guinea pigs. Kidney tissue was utilized as a known positive control. METHODS: The techniques of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry were utilized to examine the expression of GR mRNA and protein. To assure the presence of olfactory mucosa in the nasal tissue samples, RT-PCR was utilized to identify the olfactory marker protein (OMP). RESULTS: The presence of GR mRNA was confirmed in both the olfactory mucosa and kidney. GR-like immunoreactivity associated with the olfactory epithelium was greatest at the apical surface, a position corresponding to the dendrites, knobs, and cilia of olfactory receptor neurons, as well as the supranuclear region of sustentacular cells. Weaker GR-like immunoreactivity was associated with the region of the cell bodies of the olfactory receptor neurons. Within the lamina propria, acinar cells of the Bowman's glands and olfactory nerve bundles were intensely immunoreactive. CONCLUSIONS: The presence of GR mRNA and protein within the olfactory mucosa is consistent with a functional role for glucocorticoid hormones in the systemic regulation of olfaction. Furthermore, these studies suggest that corticosteroid medications may have direct effects on the cells of the olfactory mucosa in the pathologic state. The potential mechanisms whereby these hormones may act are discussed.

Animals↗

Peptides as putative excitatory neurotransmitters: carnosine, enkephalin, substance P and TRH.

A number of in vitro preparations of the central nervous system have been used to characterize with intracellular recording the cellular actions of four neuropeptides. Carnosine, the putative excitatory neurotransmitter of olfactory nerves, was found to exert little or no effect in the turtle or the frog olfactory bulb, suggesting that this peptide may have other roles, e.g. neurotropic, in this system. Substance P and TRH were found to have some characteristics of a classical excitatory transmitter since they increase membrane conductance and depolarize frog motoneurons by a direct action. However, the slow time course and subthreshold nature of the depolarization may imply that these peptides function in a background manner to set the level of excitability of motoneurons. Finally, the effects of enkephalin on a variety of inhibitory systems have been examined. Enkephalin excites hippocampal pyramidal cells indirectly by blocking both spontaneous and evoked inhibitory potentials. In addition, both feedforward and feedback inhibitory pathways are depressed by enkephalin. All these effects are blocked by naloxone. Blockade of inhibitory pathways by enkephalin appears to be a general phenomenon, since similar depressant effects were seen for dendrodendritic inhibition in olfactory bulb mitral cells as well as for presynaptic inhibition of spinal primary afferents. These results indicate that neuroactive peptides can affect principal neurons by increasing their excitability via either subthreshold excitation or disinhibition.

Action Potentials↗

Marking of olfactory axons of fishes by intravital staining with Procion brilliant yellow.

Olfactory axons of fishes can be traced after vital staining of the olfactory surface with the fluorescent dye Procion brilliant yellow M 4-RAN. Following selective accumulation by the receptor dendrites and perikarya the dye migrates intra-axonally over distances of more than 200 micrometer. Fluorescence microscope observation of formaldehyde fixed and paraffin sectioned preparations of the olfactory organ demonstrate clearly the system of intraepithelial axons and their first order bundles running toward the olfactory nerve.

Animals↗

Retinal projections throughout optic nerve regeneration in the ornate dragon lizard, Ctenophorus ornatus.

In goldfish and frog, optic nerve regeneration is successful, with restoration of retinotopic projections in visual brain centres and the return of functional vision within 1-2 months. By contrast, at 1 year after unilateral optic nerve crush in the ornate dragon lizard (Ctenophorus ornatus), the regenerated retinotectal projections lack topographic order, presumably explaining why the lizards are blind via the experimental eye (Beazley et al. [1997] J. Comp. Neurol. 377:105-120). To determine whether other abnormalities are associated with the inability to restore topographic projections in the lizard, we charted anatomically the time course, accuracy, and stability of optic nerve regeneration by examining visual projections with the lipophillic dye 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI) applied to the optic disk at intervals up to 1 year after optic nerve crush; in addition, DiI tracing of small groups of axons was used to examine the topicity of axons projecting to the tectum. Axons re-innervated visual centres from between 1 and 2 months, a time frame comparable with that in goldfish and frog. However, the projections in lizard were found to differ from those in goldfish and frog in three major ways. First, there was considerable variability within the projection patterns both between individual lizards at any one stage and with time. Second, the projections were inaccurate. As in normal lizards, the major projection was to the contralateral optic tectum, although it lacked detectable retinotopic axon order throughout. Furthermore, misrouting occurred such that regenerating axons formed a persistent projection to the ipsilateral side of the brain that was considerably stronger and more widespread than normal. Minor visual centres also became re-innervated but, in addition, regenerating axons formed persistent projections into the opposite optic nerve and to non-retino-recipient regions such as the nucleus rotundus, hypothalamus, and olfactory nerve, as well as the posterior and tectal commissures. Third, the projections appeared unstable. Projections to both tecta were strongest between 3 and 5 months, but they diminished thereafter. The results suggest that, compared with goldfish and frog, in lizards both pathway and target cues are degraded and/or cannot be read adequately; as a consequence, regenerating axons are unable to navigate exclusively to visual centres and cannot re-form stable connections.

Animals↗

[Development of human olfactory receptors].

The development of the olfactory epithelium in 7-, 8-, 9-, 10- and 11-week old human fetuses was followed using electron microscopy. The differentiation of receptor and supporting cells and the establishment of Bowman's glands and the formation of olfactory nerve have been observed. In 7 week old fetuses the development of peripheral processes with olfactory knobs, lacking hairs, and of central processes with growth cones penetrating the connective tissue has been followed. A typical olfactory knobs possessing hairs were first found in 9 week old fetuses, the number of those progressively increasing starting from the 10 week age. At the 11th week of the development, completely differentiated olfactory cells were found, which are suggested to be capable of normal olfactory performance.

Cell Differentiation↗

Development of the olfactory epithelium in man.

The development of the olfactory epithelium in 7-, 8-, 9-, 10- and 11-week-old human fetuses was studied by electron microscopy. The differentiation of the receptor and supporting cells, and formation of the Bowman glands and the olfactory nerve were observed. In 7-week-old fetuses develop the peripheral processes with the olfactory knobs lacking hairs, as well as the central processes with the growth cones. The olfactory knob with hairs was first found in 9-week-old fetuses, their number progressively increasing starting from the 10th week. The completely differentiated olfactory cells were found by the 11th week. They are suggested to be capable to carry out the olfactory function.

Epithelial Cells↗

A comparison of the discriminatory ability and sensitivity of the trigeminal and olfactory systems to chemical stimuli in the tiger salamander.

Trigeminal receptors can respond to a wide variety of chemical stimuli, but it is unknown whether these receptors mediate discrimination between chemical stimuli matched for equal perceptual intensity. The present electrophysiological and behavioral experiments address this issue using tiger salamanders, Ambystoma tigrinum, and four compounds (amyl acetate, cyclohexanone, butanol, and d-limonene). In addition, the relative sensitivities of the trigeminal and olfactory systems to these compounds are compared. In electrophysiological cross-adaptation experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), there was complete cross adaptation such that only concentrations above the background (cross-adapting) stimulus concentration elicited responses, suggesting that chemical stimuli may stimulate trigeminal receptors nonspecifically. In behavioral experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), only animals with intact olfactory nerves could discriminate between perceptually equivalent concentrations, that is concentrations that elicited the same level of responding. Both electrophysiologically and behaviorally, the trigeminal system exhibited higher thresholds than the olfactory system. We conclude that trigeminal chemoreceptors, at least in salamanders, are unable to discriminate between these two pairs of compounds when matched for equal perceptual intensity, and that trigeminal chemoreceptors are less sensitive than olfactory receptors.

Action Potentials↗

Immunohistochemical localization of gonadotropin releasing hormones in the brain and pituitary gland of the Nile perch, Lates niloticus (Teleostei, Centropomidae).

In the present study we investigated the distribution of gonadotropin-releasing hormones (GnRH) in the brain of Lates niloticus and their association with different pituitary cell types using immunohistochemical techniques. We found immunoreactive (ir) chicken GnRH-II (cGnRH-II) and mammalian GnRH (mGnRH) as the main components of the GnRH-ir system within the brain of the Nile perch. The results indicate that mGnRH and cGnRH are localized in different neurons: mGnRH-ir perikaria were observed in the preoptic region particularly in the organum vasculosum laminae terminalis (OVLT) and in the nucleus lateralis tuberis pars posterior (NLTP) of the mediobasal hypothalamus. These cell bodies are located along a continuum of ir-fibers that could be traced from the olfactory nerve to the pituitary. mGnRH-ir fibers were detected in many parts of the brain (olfactory bulbs, ventral telencephalon, hypothalamus, and mesencephalon) and in the pituitary. cGnRH-ir cell bodies are restricted to the optic tract, but few scattered fibers could be detected in different parts of the brain. The pituitary exhibited very few cGnRH-II ir fibers, contrasting with an extensive mGnRH innervation. Moreover, mGnRH-ir fibers were targeting the three areas of the pituitary gland: rostral pars distalis (RPD), proximal pars distalis (PPD), and pars intermedia (PI). Double immunolabeling studies showed GnRH-ir fibers in close proximity with prolactin (PRL)- and adrenocorticotropic hormone (ACTH)-producing cells in the RPD, growth hormone (GH)-producing cells in the PPD, gonadotropins (GTHs)-producing cells in the PPD in the external border of the PI, and with somatolactin (SL)- and alpha-melanocyte stimulating hormone (alpha-MSH)-producing cells in the PI. Our results showed direct morphological evidence for a close association of GnRH-ir fibers with the different adenohypophysial cell types. These results suggest a multiple role of GnRH in the regulation of various pituitary hormones' release.

Animals↗

Thyrotropin-releasing hormone (TRH)-immunoreactive neuron populations in the rat olfactory bulb.

Thyrotropin-releasing hormone (TRH)-like immunoreactivity was examined in the rat olfactory bulb by an immunohistochemical method using antiserum against the tripeptide TRH. TRH-immunoreactive neurons and neuronal processes were localized in both main and accessory olfactory bulb, including the glomerular layer, external plexiform layer, mitral cell body layer, internal plexiform layer and granule cell layer. However, no TRH-positive structures were observed in the olfactory nerve layer. The present study demonstrates that TRH is located in several neuronal populations in the olfactory bulb, and that this peptide thus may be involved in the processing of information in the olfactory system.

Animals↗

EMX1 homeoprotein is expressed in cell nuclei of the developing cerebral cortex and in the axons of the olfactory sensory neurons.

We analyzed the distribution of EMX1 during mouse development. EMX1 is a homeoprotein encoded by Emx1, a regulatory homeobox gene expressed in the developing forebrain. Its distribution essentially overlaps the expression domains of Emx1 transcripts. The EMX1 protein is present in the developing dorsa telencephalon, that is in the cerebral cortex, olfactory bulb and hippocampus. In the cerebral cortex EMX1 is present in nuclei of proliferating, differentiating and most mature neurons belonging to all cortical layers. In the olfactory bulb it is present in all proliferating cells during development, whereas postnatally it is faintly expressed in some mitral cells. Non-cerebral localizations include a transient expression in branchial pouches, in the apical ectodermal ridge of the developing limbs and in the developing kidney. Of particular interest is the presence of EMX1 in the olfactory nerve from its first appearance during embryogenesis to birth. The protein is present in axons of olfactory sensory neurons along their entire length, including their terminals in spherical regions of neuropil in the olfactory bulb called glomeruli.

Animals↗

Calcification of the olfactory bulbs in three patients with hyposmia.

An estimated two million Americans suffer from chemosensory disorders. We present the clinical and imaging findings in three hyposmic patients with bilateral olfactory bulb calcification detected by CT. To our knowledge, these are the first cases of olfactory bulb calcification reported in the literature. A review of the literature concerning calcification of cranial nerves, olfactory neuritis, and the potential etiology and clinical significance of olfactory bulb calcification in our patients is presented.

Adult↗

Direct evidence for the migration of LHRH neurons from the nasal region to the forebrain in the chick embryo: a carbocyanine dye analysis.

To examine the possible migration of luteinizing hormone-releasing hormone (LHRH) neurons from the olfactory placode to the brain, the epithelial cells of the olfactory placode of the chick embryos were labeled with a fluorescent carbocyanine dye DiI at embryonic days 3.5-4.0. The embryos treated with DiI were incubated in ovo for 1 to 7 days. The DiI-labeled cells were first detected in the olfactory epithelium and olfactory nerve one day after the application of DiI. Two to four days after the application of the dye, the labeled cells sequentially appeared in the rostral and medial forebrain, and in the septo-preoptic area. The distribution pattern of DiI-labeled cells closely resembled that of LHRH neurons. Double staining for DiI and LHRH demonstrated that DiI-labeled cells co-expressed LHRH. However, there were a number of DiI-labeled cells which did not co-express LHRH. These results provide evidence for the actual migration of LHRH neurons from the olfactory placode to the septo-preoptic area during the development, and also suggest that some non-LHRH neurons in the forebrain are of olfactory placodal origin.

Animals↗