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At least 1,153 records · Page 64Linked to original sources
PubMed2006

Development of wiring specificity in the olfactory system.

The olfactory system discriminates a large number of odorants using precisely wired neural circuits. It offers an excellent opportunity to study mechanisms of neuronal wiring specificity at the single synapse level. Each olfactory receptor neuron typically expresses only one olfactory receptor from many receptor genes (1000 in mice). In mice, this striking singularity appears to be ensured by a negative feedback mechanism. Olfactory receptor neurons expressing the same receptor converge their axons to stereotypical positions with high precision, a feature that is conserved from insects to mammals. Several molecules have recently been identified that control this process, including olfactory receptors themselves in mice. The second order neurons, mitral cells in mammals and projection neurons in insects, have a similar degree of wiring specificity: studies in Drosophila suggest that projection neuron-intrinsic mechanisms regulate their precise dendritic targeting. Finally, recent studies have revealed interactions of different cell types during circuit assembly, including axon-axon interactions among olfactory receptor neurons and dendro-dendritic interactions of projection neurons, that are essential in establishing wiring specificity of the olfactory circuit.

Animals↗
PubMed2004

Theoretical consideration of olfactory axon projection with an activity-dependent neural network model.

Olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) target their axons onto a few specific glomeruli in the olfactory bulb. Although the odorant receptor plays an indispensable role in olfactory axon targeting, the mechanisms underlying this guidance are largely unknown. In particular, there is much controversy regarding the involvement of activity-dependent mechanism in the targeting process. In this study, we developed an activity-dependent self-organization model of the glomerular layer in the olfactory bulb and simulated the targeting of olfactory axons onto the layer. Our model successfully constructed discrete glomeruli that received olfactory axons expressing a common odorant receptor through odorant-evoked neural activities. Furthermore, our model explained the perplexing experimental results that have been reported in olfactory axon targeting. For example, dispersion of olfactory axons in knockout mice for the odorant receptor gene was reasonably reproduced in the simulation. The segregated projection of the axons that express the same odorant receptor transcribed from the different alleles was also successfully simulated if the genetically modified allele was assumed to express a smaller amount of the receptor protein. The activity-dependent model even explained the inconsistent effects of disruption of the activity-evoking ion channel on axons expressing different odorant receptors, although some of these results were regarded as evidence for activity-independency of the olfactory targeting. Taken together, the activity-dependent targeting of olfactory axons seems to be a simple probable mechanism that can provide a unified explanation of glomerular formation.

Action Potentials↗
PubMed2006

Disrupted compartmental organization of axons and dendrites within olfactory glomeruli of mice deficient in the olfactory cell adhesion molecule, OCAM.

There is an overall topographic connectivity in the axonal projections of olfactory sensory neurons from the olfactory epithelium (OE) to the olfactory bulb (OB). The molecular determinants of this overall topographic OE-OB connectivity are not known. For 20 years, the intriguing expression pattern of the olfactory cell adhesion molecule (OCAM) has made it the leading candidate as determinant of overall topographic OE-OB connectivity. Here, we have generated a strain of OCAM knockout mice by gene targeting. There were no obvious alterations in the distribution of olfactory sensory neurons within the OE or in the coalescence of axons into specific glomeruli. However, the compartmental organization of dendrites and axons within the glomeruli was disrupted. Surprisingly, the mutant mice exhibited an increase in olfactory acuity; they appeared to have a better sense of smell. Thus, despite its striking expression pattern, OCAM is not essential for overall topographic OE-OB connectivity. Instead, OCAM is required for establishing or maintaining the compartmental organization and the segregation of axodendritic and dendrodendritic synapses within glomeruli.

Animals↗
PubMed2006

Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in olfactory and vomeronasal chemosensory neurons in vivo.

A role for the US3 protein kinase of herpes simplex virus (HSV) in regulating virus-induced neuronal apoptosis was investigated in an experimental mouse system, in which wild-type HSV invades the central nervous system (CNS) via the olfactory and vomeronasal systems upon intranasal infection. Wild-type HSV-2 strain 186 infected a fraction of olfactory and vomeronasal chemosensory neurons without inducing apoptosis and was transmitted to the CNS, precipitating lethal encephalitis. In sharp contrast, an US3-disrupted mutant, L1BR1, induced neuronal apoptosis in these peripheral conduits upon infection, blocking viral transmission to the CNS and causing no signs of disease. An US3-repaired mutant, L1B(-)11, behaved similarly to the wild-type virus. Only 5 p.f.u. of L1BR1 was sufficient to compromise mice when the mutant virus was introduced directly into the olfactory bulb, a viral entry site of the CNS. These results suggest that the US3 protein kinase of HSV regulates virus-induced neuronal apoptosis in peripheral conduits and determines the neuroinvasive phenotype of HSV. Furthermore, virus-induced neuronal apoptosis of peripheral nervous system cells may be a protective host response that blocks viral transmission to the CNS.

Animals↗
PubMed2006

Characterization of the expression of the ALK receptor tyrosine kinase in mice.

Anaplastic Lymphoma Kinase (ALK), a receptor tyrosine kinase, was first described as the fusion product causing a subtype of non-Hodgkin's lymphoma. To date Alk has been reported to be mainly expressed in CNS and other parts of the brain. Here we describe an extensive characterization of the mRNA and protein expression of ALK during mouse development. We show that mRNA and ALK protein show overlapping expressing patterns in specific regions of the central and the peripheral nervous systems. Furthermore, ALK is also expressed in the eye, nasal epithelium, olfactory nerve, tongue, skin, tissue surrounding the esophagus, stomach and midgut but not the hindgut. Expression of ALK is also found in testis and ovary.

Anaplastic Lymphoma Kinase↗
PubMed2005

Identification and distribution of mouse carboxypeptidase A-6.

Carboxypeptidase A-6 (CPA6) was recently discovered in the human genome. To gain information regarding the potential function of this novel protein, the mouse homolog of CPA6 was identified using a combination of bioinformatics and reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, homologs in rat, chicken, and frog were identified using a bioinformatics approach. The distribution of CPA6 mRNA in mouse tissues was examined using RT-PCR and in situ hybridization. A strong RT-PCR signal is detectable in olfactory bulb, and much lower levels are present in other regions such as the cerebral cortex, hippocampus, hypothalamus, striatum, and medulla. In peripheral tissues, a moderate RT-PCR signal is present in epididymis, and low levels are detectable in colon and spleen. The high level of CPA6 in adult mouse brain olfactory bulb was confirmed by in situ hybridization. Lower levels of CPA6 mRNA were found to be present in the cingulate cortex, lateral septum, pontine nucleus, and inferior olivary nucleus of the hindbrain. Within the olfactory bulb, CPA6 mRNA is enriched in the mitral and granular layer. A lower level of CPA6 mRNA is present in the internal and external plexiform layers, and no signal is detectable in the olfactory nerve layer. The distribution was also examined in whole embryos at embryonic day 14.5 and CPA6 mRNA was found to be enriched in eye, ear, osteoblasts, stomach, skin, dorsal root ganglia, and throughout the CNS. The presence of CPA6 mRNA in the rectus muscle layer of the eye at embryonic day 14.5 is consistent with the observation that the CPA6 gene is disrupted in a patient with Duane syndrome, a congenital eye defect. Taken together, the distribution of CPA6 suggests a specific role in a limited number of tissues, and it is possible that this role involves an aspect of cell migration.

Animals↗
PubMed2006

Formation of glomerular maps in the olfactory system.

Sensory perception relies on the decoding of external stimuli into an internal neuronal representation, which requires precise connections between the periphery and the brain. In the olfactory system the axons of chemosensory neurons with the same odorant receptor coalesce into common glomeruli in the olfactory bulb, forming a receptor-topic map. The creation of this map begins prenatally when axons navigate towards the bulb, resort in a receptor-specific manner and terminate in a broad area interdigitated with other axon populations; distinct glomeruli form postnatally. While the initial process of glomerulization requires mainly molecular determinants, activity-dependent processes lead to a refinement of glomerular organization.

Animals↗
PubMed2004

Molecular mechanisms of gonadotropin-releasing hormone neuronal migration.

Gonadotropin-releasing hormone (GnRH) neurons originate in the nasal compartment, migrate along olfactory nerves to the cribriform plate and then diverge caudally to the forebrain to reach their final destination in the hypothalamus. Here, GnRH neurons are dispersed in a network that synchronously releases GnRH in a pulsatile manner to activate pituitary gonadotropin production. Gonadotropins in turn promote gametogenesis and steroidogenesis from the gonad, ensuring reproductive competence. Failure of GnRH neurons to migrate normally results in deficient activation of the reproductive axis and delayed or absent pubertal maturation. The exact mechanisms that direct GnRH neuronal migration are under active investigation. This article will review new information concerning factors regulating GnRH neuronal migration and the intracellular signaling pathways involved in this process.

Animals↗
PubMed2006

A chimpanzee-origin adenovirus vector expressing the rabies virus glycoprotein as an oral vaccine against inhalation infection with rabies virus.

Rabies has the highest fatality rate of all human viral infections and the virus could potentially be disseminated through aerosols. Currently licensed vaccines to rabies virus are highly effective but it is unknown if they would provide reliable protection to rabies virus transmitted through inhalation, which allows rapid access to the central nervous system upon entering olfactory nerve endings. Here we describe preclinical data with a novel vaccine to rabies virus based on a recombinant replication-defective chimpanzee-origin adenovirus vector expressing the glycoprotein of the Evelyn Rokitniki Abelseth strain of rabies virus. This vaccine, termed AdC68rab.gp, induces sustained central and mucosal antibody responses to rabies virus after oral application and provides complete protection against rabies virus acquired through inhalation even if given at a moderate dose.

Adenoviridae↗
PubMed2004

[Olfactory disorders].

Smell and taste problems are of major importance to those who suffer from olfactory disorders. The inability to determine the presence of odors in the home and the markedly reduced capacity or incapacity to appreciate food flavors are key reasons given for limited social interaction. Patients experiencing distorted smells and tastes may avoid food, which results in weight loss and possible malnutrition. We present an overview of smell disorders, based on physiological considerations, with specific attention to clinical characteristics of conditions most commonly causing smell disorders.

Adult↗
PubMed2001

Modulation of oscillatory neural activities by cholinergic activation of interneurons in the olfactory center of a terrestrial slug.

The neurons in the procerebrum (PC) of the terrestrial slug Limax marginatus show regular oscillation of their membrane potential, and the oscillation has been implicated in olfactory processing. The neural mechanisms for the generation and modulation of the oscillation have been poorly understood. In the present work, we examined the ionic conductances evoked by acetylcholine (ACh) in the PC neurons and the effects of ACh application on the population activities of intrinsic and extrinsic neurons. The PC neurons are categorized into bursting neurons, which are putative local inhibitory neurons, and nonbursting neurons, which likely mediate the input and output of information in the PC. Bath application of ACh augmented the local field potential oscillation in the PC. Perforated patch recording from single PC neurons revealed that ACh has direct excitatory effects on bursting neurons, while it suppresses the activity of nonbursting neurons, possibly via augmented inhibitory synaptic input from bursting neurons. The correlation between the membrane potential of bursting neurons and the frequency of oscillation suggests that bursting neurons are the main determinant of the oscillation frequency. Application of ACh also resulted in a reduction of the oscillation amplitude in the olfactory nerve, suggesting that the frequency modulation in the oscillatory network could change the activities in the follower neurons.

Acetylcholine↗
PubMed1997

Laminins of the adult mammalian CNS; laminin-alpha2 (merosin M-) chain immunoreactivity is associated with neuronal processes.

Laminins are glycoproteins with three subunits, i.e. a longer alpha chain, a shorter beta chain and a shorter gamma chain. Well-characterized laminins are laminin-1 (EHS laminin; alpha1-beta1-gamma1), laminin-2 (merosin; alpha2-beta1-gamma1), laminin-3 (alpha1-beta2-gamma1) and laminin-4 (alpha2-beta2-gamma1). The present study shows that in the adult mammalian CNS (rat, rabbit, pig and monkey) alpha2 chain immunoreactivity is associated most evidently with neuronal fibers and punctate, potentially synaptic, structures of limbic brain regions. Third ventricle tanycytes and ensheathing cells of the olfactory nerve also express intense alpha2 chain immunoreactivity. Immunostaining for gamma1 chain is present throughout the central nervous system (CNS) in essentially all neuronal cell bodies and their most proximal processes. Immunoreactivity for all chains investigated (alpha1, alpha2, beta1, beta2 and gamma1) were present around blood vessels, especially evident in lightly fixed tissues. The finding that, other than blood vessels, neurons and other structures exhibited immunoreactivity for only one or two (and not three) chains, suggests that variant forms of laminin with yet undiscovered chains or other configurations than the heterotrimeric form are present in the CNS. The association of alpha2-like immunoreactivity with neuronal fibers and synaptic structures is of great interest in light of the known neurite-promoting and cell attachment activities of laminin-2.

Animals↗
PubMed2002

Cloning of the cDNA for the putative calcium-sensing receptor and its tissue distribution in sea bream (Sparus aurata).

The cDNA for the calcium-sensing receptor (CaSR) gene has been cloned from the marine teleost Sparus aurata, the sea bream. The isolated clones were 3.3 kb long with an open reading frame of 2820 bp, a 5' UTR of 240 bp, and 3' UTR of 248 bp. The gene codes for a mature peptide of 940 amino acids which has three principal domains; the extracellular region is more than half the total protein, there is a seven-transmembrane domain, and there is a short intracellular domain. There is considerable sequence identity, 91%, shared between the CaSR of sea bream and puffer fish but overall similarities with mammalian CaSR peptides vary between 44% for rat and mouse and 48% with human CaSR. Nevertheless, the 18 cysteine residues of the extracellular domain are present in all sequences so far analysed of which 9 form a cysteine-rich region in sea bream similar to mammalian CaSR. The distribution of CaSR in sea bream tissues detected by in situ hybridisation showed gene expression in epithelia associated with ion transport or ion regulation including the hind gut, chloride cells of the gills, operculum, gall bladder, pituitary adenohypophysis, and coronet cells of the saccus vasculosus; this distribution was confirmed by RT-PCR. By in situ hybridisation, CaSR gene expression was also present in olfactory nerves and leucocytes.

Amino Acid Sequence↗
PubMed2000

Olfactory sensitivity and specificity of Arctic char, Salvelinus alpinus, to a putative male pheromone, prostaglandin f(2)alpha.

Actively spawning male Arctic char, Salvelinus alpinus, release immunoreactive F-prostaglandins into the water that attract ovulated females and elicit spawning behaviour. To investigate a possible role played by the olfactory system, we determined the sensitivity and specificity of the char to prostaglandins by the electro-olfactogram (EOG) using a newly devised stimulatory apparatus. Of 18 prostaglandins tested, PGF(2)alpha and two synthetic analogues, 16,16-dimethyl-PGF(2)alpha and U-46619, were detected at threshold concentrations of 0.5-1.0 x 10(-11) M, and at a concentration of 10(-8) M evoked an EOG response equivalent to that of 10(-5) M L-serine. Olfactory nerve twig recordings further demonstrated that the EOG responses were transduced into nerve impulses and transmitted to the brain. No difference was found in the responses between sexes and maturational stages. We conclude that PGF(2)alpha is a candidate of the male pheromone of Arctic char, supporting our previous behavioural studies.

Aging↗
PubMed2002

Bilateral supraorbital keyhole approach for multiple aneurysms via superciliary skin incisions.

BACKGROUND: Considering that multiple aneurysms carry a high risk for fatal rupture, there is a need for complete treatment of all lesions in one surgical session using either unilateral-contralateral or bilateral approaches. Contralateral approaches have been used mainly for small anteriorly projecting middle cerebral and medially expanding ophthalmic types of aneurysms. They are limited by the narrow space for surgical manipulation, forced elevation of frontal lobes, and stretching of the olfactory nerves. These problems might result in damage to structures along the unusually long intracranial way of the approach. The complications associated with the unnecessarily large conventional fronto-temporal and bifrontal craniotomies, and the developments in visualization, neuroanaesthesia, microneurosurgery, cerebrospinal fluid (CSF) drainage, and brain protection have led to less invasive methods in cerebral base surgery. These achievements have supplied the background for the supraorbital keyhole approach to aneurysms of the anterior circulation or basilar tip. Because the supraorbital keyhole approach offers several advantages over the classic fronto-temporal craniotomies to the anterior skull base, it was extended for both sides in one surgical session to treat bilateral multiple aneurysms as well. METHODS: Out of a series of 150 patients harboring 188 saccular aneurysms operated on via a supraorbital keyhole approach with a superciliar skin incision, 36 had multiple aneurysms. Thirty patients with multiple aneurysms underwent surgery for their ruptured aneurysms (17 cases in the acute phase and 13 patients during the chronic stage); in 6 cases silent aneurysms were operated on. The multiple aneurysms were managed from one side in 18 cases. A bilateral supraorbital keyhole approach was performed during one surgical session in 11 patients, and in 7 cases the unilateral supraorbital keyhole approach was combined with contralateral fronto-temporal (3 cases), suboccipital (2 cases), or frontal-parasagittal (2 cases) exploration. The operations were carried out through an approximately 2.5 x 3 cm supraorbital keyhole craniotomy following a skin incision just above the eyebrow. The roughly 4 cm superciliar skin incision begins medial to the supraorbital nerve and ends 3 to 10 mm beyond the lateral edge of the eyebrow. The technical details of the method are presented, and the benefits, limitations, and complications are discussed. RESULTS: In the 36 patients operated on via the supraorbital keyhole approach 74 aneurysms were clipped successfully. In 2 cases premature intraoperative rupture of the aneurysms occurred, but these events were managed successfully. Despite the small size of the craniotomy the approach allows enough room for intracranial manipulation with maximal protection of the brain and other intracranial structures. One patient died because of pulmonary embolism. There were no craniotomy-related complications in the present series. CONCLUSION: The supraorbital keyhole approach together with the advent of the modern neuroanaesthesia, CSF drainage, and microsurgical techniques is a safe approach in the hands of experienced neurosurgeons for the treatment of supratentorial or basilar tip aneurysms. Because the approach is simple and swift, the bilateral single-session craniotomy does not have any disadvantages compared to two-stage procedures. However, the one-sitting surgery reduces the high risk of fatal rupture in the perioperative period associated with multiple aneurysms.

Cerebral Angiography↗
PubMed2001

EphB2 and two of its ligands have dynamic protein expression patterns in the developing olfactory system.

Primary olfactory neurons are located in the olfactory neuroepithelium lining the nasal cavity. Their axons converge and form glomeruli with the dendrites of second-order neurons in the olfactory bulb. The molecular basis of primary olfactory axon guidance, targeting and subsequent arborisation is largely unknown. In this study we examined the spatio-temporal expression of the Eph receptor EphB2 and its ligands, ephrin-B1 and ephrin-B2, during development of the rat primary olfactory system. Unlike in other regions of the nervous system where receptor and ligand expression patterns are usually non-overlapping, EphB2, ephrin-B1 and ephrin-B2 were all expressed by primary and second-order olfactory neurons. In the embryonic animal we found that these three proteins had distinct and different expression patterns. EphB2 was first expressed at E18.5 by the perikarya of primary olfactory neurons. In contrast, ephrin-B1 was expressed from E13.5 and was localised to the axons of these cells up to E18.5 but was then restricted to the perikarya. Ephrin-B2, however, was expressed by olfactory ensheathing cells. EphB2, ephrin-B1 and ephrin-B2 were also expressed in the prenatal olfactory bulb and were restricted to the perikarya of mitral cells. In the post-natal olfactory bulb there was a shift in the localisation of both EphB2 and ephrin-B1 to the dendritic arborisations of mitral cells. The dynamic and tightly regulated spatio-temporal expression patterns of EphB2, ephrin-B1 and ephrin-B2 by specific olfactory cell populations suggest that these molecules have the potential to regulate important developmental events in the olfactory system.

Animals↗
PubMed1998

Development of NADPH-diaphorase expression in chemosensory systems of the opossum, Monodelphis domestica.

Using NADPH-diaphorase histochemistry, the present study describes development of olfactory and vomeronasal systems in postnatal opossums, Monodelphis domestica. NADPH-dependent staining is absent at and around the time of birth. By 2 weeks of age and through adulthood, intense staining is seen along the luminal surface of the olfactory epithelium (OE) and of the vomeronasal sensory epithelium (VNE), as well as in Bowman's glands of the OE. Staining of the adult VNE is not homogeneous; it is restricted to the superficial 2/3 of the epithelium. At 2 weeks of age, staining in the brain is seen only at the surface of the ventricles and in blood vessels. At 1 month of age and through adulthood, staining of varying intensity is seen in individual olfactory bulb glomeruli, although the incoming olfactory axons are relatively unstained. Interestingly, whereas at 30 days of age, staining of the accessory olfactory bulb (AOB) glomeruli is uniform, 2 weeks later and in the adult, NADPH staining is concentrated in the rostral half, with little or no staining observed in the posterior portion. Darkly stained periglomerular cells are seen throughout the extent of the differentially-stained glomerular layer. From 30 days of age and through adulthood, intense NADPH staining is also observed in the islands of Calleja, as well as in cells of the dorsal cortex, often associated with the path of the rostral migratory stream.

Aging↗