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PubMed2002

Atrial natriuretic peptide type C induces a cell-cycle switch from proliferation to differentiation in brain-derived neurotrophic factor- or nerve growth factor-primed olfactory receptor neurons.

With the discovery of postnatal stem cells within the brain, it has become important to understand how extracellular factors might affect the maturation of neuronal precursors in the postnatal brain. Neurotrophic factors are known to play a role in neuronal development but display pleiotrophic effects, in part because of their physiological interactions with other factors. One factor positioned to interact with neurotrophins in the brains of postnatal animals is atrial C-type natriuretic peptide (CNP). In this study, we used olfactory receptor neurons (ORNs) as a model, because their precursors demonstrate the most robust and functional postnatal neurogenesis of those systems thus far described. We examined the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and the interactions of these neurotrophins and CNP in postnatal olfactory neuronal precursors. Results obtained using mice with targeted deletion of the gene for BDNF indicated that BDNF is a neuroproliferation-inducing and survival factor for ORN precursors. These roles were confirmed in vitro using primary cultures of ORNs. NGF was found to be a proliferation-inducing factor but not a survival factor. The addition of CNP to either BDNF- or NGF-treated neuronal precursors resulted in an inhibition of proliferation and the promotion of maturation. These effects were accompanied by changes in cell-cycle proteins that suggest possible mechanisms for these effects. Thus, CNP may function in the postnatal brain to regulate the exit from the cell cycle in neuronal precursor cells.

Animals↗
PubMed1998

Computation of molecular information in mammalian olfactory systems.

The olfactory system is unique in that the sensory input is in the form of molecular information carried in odour molecules and that a huge variety of compounds can function as odour molecules. The mammalian olfactory system has neuronal networks that can process and integrate the molecular information for discrimination of odour molecules and for perception of olfactory images of objects. Recent rapid advances have begun to provide new insights into the functional logic employed by the main olfactory system for odour discrimination, for odour classification and for olfactory perception of objects. This review discusses how the odour molecule information is encoded, transmitted, processed and decoded at distinct anatomical structures (sensory epithelium, olfactory bulb and olfactory cortex) of the olfactory nervous system. We also discuss the functional network in the accessory olfactory system with regard to the processing of pheromonal information.

Animals↗
PubMed1999

Odor coding in a model olfactory organ: the Drosophila maxillary palp.

Odor coding relies on the activity of different classes of receptor neurons, each with distinct response characteristics. We have examined odor coding in a model olfactory organ, the maxillary palp of Drosophila. This organ contains only 120 olfactory receptor neurons, compartmentalized in sensory hairs called sensilla, and provides an opportunity to characterize all neurons in an entire olfactory organ. Extensive extracellular recordings from single sensilla reveal that the neurons fall into six functional classes. Each of the 60 sensilla houses two neurons, which observe a pairing rule: each sensillum combines neurons of two particular classes, thereby yielding three sensillum types. The sensillum types are intermingled on the surface of the palp, but their distribution is not random. The neurons exhibit diverse response characteristics, providing the basis for an olfactory code. A particular odor can excite one neuron and inhibit another, and a particular neuron can be excited by one odor and inhibited by another. Some excitatory responses continue beyond the end of odor delivery, but responses to most odors terminate abruptly after the end of odor delivery, with some followed by a period of poststimulus quiescence. The specificity of odor response is examined in detail for the neurons of one sensillum, which were found to differ in their relative responses to a homologous series of esters. Adaptation and cross-adaptation are documented, and cross-adaptation experiments demonstrate that the two neurons within one type of sensillum can function independently. The analysis of all neuronal types in this model olfactory organ is discussed in terms of its functional organization and the mechanisms by which it encodes olfactory information.

Adaptation, Physiological↗
PubMed1999

Semaphorins and their receptors in olfactory axon guidance.

The mammalian olfactory system is capable of discriminating among a large variety of odor molecules and is therefore essential for the identification of food, enemies and mating partners. The assembly and maintenance of olfactory connectivity have been shown to depend on the combinatorial actions of a variety of molecular signals, including extracellular matrix, cell adhesion and odorant receptor molecules. Recent studies have identified semaphorins and their receptors as putative molecular cues involved in olfactory pathfinding, plasticity and regeneration. The semaphorins comprise a large family of secreted and transmembrane axon guidance proteins, being either repulsive or attractive in nature. Neuropilins were shown to serve as receptors for secreted class 3 semaphorins, whereas members of the plexin family are receptors for class 1 and V (viral) semaphorins. The present review will discuss a role for semaphorins and their receptors in the establishment and maintenance of olfactory connectivity.

Animals↗
PubMed2000

Response characteristics of an identified, sexually dimorphic olfactory glomerulus.

Partitioning of synaptic neuropil into glomeruli is a common feature of primary olfactory centers in most animal species. The functional significance of glomeruli, however, is not yet well understood. The present study is part of our effort to test the hypothesis that each glomerulus is a functional unit dedicated to processing information about a particular odorant or attribute of odor molecules and that the glomerular array constitutes a map of "odor space." We investigated the physiological and morphological features of uniglomerular projection neurons (PNs) associated with an identified glomerulus in each antennal lobe of the female sphinx moth, Manduca sexta. This "lateral large female glomerulus" (latLFG) is sexually dimorphic and therefore may play a female-specific role, such as processing of information about one or more odorants important for orientation of a female to host plants for oviposition. Together with the medial LFG (medLFG), the latLFG resides outside the array of spheroidal ordinary glomeruli, near the entrance of the antennal (olfactory) nerve. Each LFG is innervated by four to five PNs. Using intracellular recording and staining, we examined the responses of latLFG-PNs to odorants that represent major classes of volatiles released by host plants of M. sexta. All latLFG-PNs were excited when the ipsilateral antenna was stimulated with low concentrations of the monoterpenoid linalool. Dose-response analysis showed that neither other monoterpenoids nor representatives of other classes of host plant volatiles were similarly stimulatory to latLFG-PNs. These findings are consistent with the idea that each glomerulus has a characteristic, limited molecular receptive range.

Action Potentials↗
PubMed2000

Importance of timing of olfactory receptor-axon outgrowth for glomerulus development in Manduca sexta.

In the moth Manduca sexta, development of glomeruli in the antennal (olfactory) lobes (ALs) follows a precise timetable and involves interactions of olfactory receptor cell (ORC) axons with AL glial cells and neurons. To study the importance of timing for these intercellular interactions, we experimentally desynchronized the development of the ALs and the ORCs by altering the temperature of the developing antenna and brain for defined periods of time during development. Selective cooling of the antenna relative to the body resulted in a delay of ORC-axon outgrowth, and slightly warming the antenna while cooling the body caused precocious ingrowth of axons into the AL. Whereas cooling of the antenna for 24 hours caused only a delay in the formation of glomeruli, cooling for 48 hours led to significant disruption of glomerular development. Glial cells did not form normal glomerular borders, and glomeruli were shaped abnormally. Axons of pheromone-specific ORCs projected to their correct target, but terminal branches within the macroglomerular complex (MGC) were not clearly segregated. The results suggest that proper formation of glial glomerular borders requires interaction of ORC axons and glial cells within a sensitive period, whereas targeting of ORC axons appears to be effective over extended periods in development. Precocious ingrowth of ORC axons after warming the antenna and cooling the body for 48 hours resulted in enlarged protoglomeruli. Glial borders formed normally, but a subpopulation of MGC-specific ORC axons grew past the MGC. The decreased accuracy of targeting in these cases suggests that targeting mechanisms are not fully developed before the time when ORC axons normally would enter the brain.

Age Factors↗
PubMed2001

Symmetry, stereotypy, and topography of odorant representations in mouse olfactory bulbs.

The molecular basis of vertebrate odorant representations has been derived extensively from mice. The functional correlates of these molecular features were visualized using optical imaging of intrinsic signals in mouse olfactory bulbs. Single odorants activated clusters of glomeruli in consistent, restricted portions of the bulb. Patterns of activated glomeruli were clearly bilaterally symmetric and consistent in different individual mice, but the precise number, position, and intensity of activated glomeruli in the two bulbs of the same individual and between individuals varied considerably. Representations of aliphatic aldehydes of different carbon chain length shifted systematically along a rostral-caudal strip of the dorsal bulb, indicating a functional topography of odorant representations. Binary mixtures of individual aldehydes elicited patterns of glomerular activation that were topographic combinations of the maps for each individual odor. Thus the principles derived from the molecular organization of a small subset of murine olfactory receptor neuron projection patterns-bilateral symmetry, local clustering, and local variability-are reliable guides to the initial functional representation of odorant molecules.

Aldehydes↗
PubMed1975

[Chronoarchitectonic analysis of the rat brain using radioautography. I. Histogenesis of the telencephalon].

1) Isocortex We find a centrifugal type chronoarchitectonic gradient with, however, a considerable overlap between the various generations of neurons. Thus in the older, deep layers (13.5 days) of the lateral neocortex 35% of the cells are chromologically incongruous (certain are very recent: 17.5 days and more). Cell production is a continuous process and has its peak towards 15.5 days of gestation. This refutes the existence of successive waves of cells. It is not possible to give even an approximate date to the isocortical layers, for the cortical laminations and the isochrones are nor concentric. What finally characterizes this structure from a chronoarchitectonic point of view is the considerable duration of the sequence of neuron production going from 13,5 days to birth. 2) Allocortex We find a centrifugal gradient in the paleocortex. In several of the structures of which it is composed a chronoarchitectonic incongruity can be attributed to the microneurons. It is the case with the islands of CALLEJA (in the olfactive tubercule) which separate very late on. In the archicortex the dominant gradient is again centrifugal. Here we find horizontal variations of the chronoarchitectonic patterns which are discussed with reference to the conception of a possibly fragmented cortex. 3) Striatum the chronoarchitectonic results largely confirm the diencephalic origin of the paleostriatum (STRASSER 1920, SPATZ 1921). In the archistriatum we find a steep rostrocaudal gradient, while the chronoarchitectonic heterogeneity of the structure tends to confirm the conception of a mixed origin (striatum and paleopallium). 4) Claustrum there is a real chronoarchitectonic incongruity between this structure and the isocortex. On one hand the sequence of the anterior part of the claustrum is of the paleostriate type. The posterior part is more probably archistriate. These findings suggest that the formation of the claustrum is of hybrid origin. 5) Septum The characteristic gradient of this formation is caudorostral. This gradient is practically common to all the structures except the telencephalon. We also find a centrifugal gradient related to the presence of a recent "cortex" which could be the counterpart of the cortical septal nuclei in superior mammals.

Amygdala↗
PubMedDate not supplied

[Pheromones: an underestimated communication signal in humans].

The pheromones are molecules, mainly aliphatic acids, with or without perceptible odor, recognized by specific receptors, the stimulation of which induces neuroendocrine reactions and affects the individual behavior. Olfactory receptors are underexpressed in human, 70 % of genes have become nonfunctional pseudogenes. But the remaining function was tested and is able to induce emotional reactions corresponding to a non-verbal signal of social interactions. In the present study, we review the actual knowledge on the olfactory receptors. They belong to the G-protein-coupled-receptors. Their signal is transduced to the hypothalamic-pituitary-gonadal axis. Some HLA-based olfactory cues are shown with reference to recent experiments. The pathophysiological hypotheses are considered with respect to studies in anorexia nervosa and Alzheimer' disease.

Animals↗
PubMedDate not supplied

[Protocortex versus protomap: a perspective from the olfactory bulb].

INTRODUCTION AND AIM: The olfactory sensory system is a unique model for the research of guidance and connectivity of growing axons. During development, the olfactory epithelium, the olfactory bulb and the olfactory cortex differentiate several cell types and extend projection axons. Because there is a close relationship between these three structures, we ask the question as to whether establishment of the olfactory bulb central projections can proceed independently of the arrival of the olfactory sensory afferents. This raises another more general question: is establishment of afferent connections necessary to awake a developmental program in target cells?. DEVELOPMENT: The initial establishment of the olfactory bulb central projections occurs independently of the arrival of the olfactory axons from the olfactory epithelium, which reinforces the idea that cortical regions are already patterned before migration of newborn neurons, at least for the olfactory bulb and maybe for the entire brain. This implies a strict intrinsic molecular control of the distinct olfactory structures, independent one of each other. CONCLUSIONS: How then, do axonal projections find their correct way within the brain? Contact-mediated mechanisms and chemotropic molecules cooperate to fix their position in the telencephalon, prevent bulbar axons from invading structures other than the olfactory cortex and, at the same time, stimulate axonal branching in an orchestra of both, attractive/promoting and repulsive/inhibiting signals. At later stages, the mature appearance of the olfactory bulb will be completed and refined.

Animals↗
PubMed2005

The effect of intramuscular injections of boar pheromone 5alpha-androstenol on the hormonal regulation of the estrous cycle in hypoosmatic gilts.

Until 1999 it was accepted that pheromones act exclusively by stimulating the dendritic receptors present in olfactory epithelium. Cycling gilts with an experimentally-disrupted neural olfactory pathway were used to test the hypothesis that boar pheromone 5alpha-androstenol may affect the secretion of hormones involved in the regulation of the estrous cycle by the humoral pathway. On day 12 of the estrous cycle the nasal cavity of gilts (n=15) was irrigated with zink sulfate solution. From day 16 to 20, the experimental group (n=10) was injected intramuscularly with 5alpha-androstenol (20 microg) twice a day. Blood samples were collected from the jugular vein at 4 h intervals on days 17-21 to estimate plasma concentration of LH, oxytocin, estradiol-17beta, testosterone and progesterone. The experimental group displayed a significantly lower mean concentration of LH than the control animals (P<0.0001). The decrease in concentration of LH was accompanied by the reduction of oxytocin (P<0.001), estradiol-17beta (P<0.001) and testosterone (P<0.01) secretion. These results demonstrated that 5alpha-androstenol influenced hormonal regulation by humoral pathway and might be considered to be the priming pheromone in gilts.

Androstenols↗
PubMedDate not supplied

Development of transgenic mouse models for the study of human olfactory dysfunction.

BACKGROUND: Olfactory loss is a significant health problem that remains incompletely understood. The development of suitable animal models is essential to the progress of human olfactory loss research. Recent advancements in transgenic technology allow the creation of model systems to address causes of olfactory neuron dysfunction. METHODS: This review describes two transgenic mouse models with potential usefulness in the study of olfactory loss and highlights the molecular techniques that underlie the development of such systems. RESULTS: Genetic constructs generated using standard molecular biological techniques are introduced into mouse germ lines either by homologous recombination or by random integration. One construct (UbI7) places the olfactory receptor I7 under control of the olfactory marker protein promoter. The other two constructs (TI) act together to direct expression of cytokines in the olfactory epithelium, creating a novel approach to the study of inflammatory olfactory loss. CONCLUSIONS: Powerful scientific tools now exist to develop animal models useful to the study of human olfactory disease. Transgenic olfactory neurons from the UbI7 mouse strain will respond to known odorants, facilitating experiments that examine in vitro modulation of olfactory neuron function. The ability to express specific genes in the olfactory mucosa of the TI mouse has great potential in elucidating the role of cytokines in the development of olfactory dysfunction in vivo.

Animals↗
PubMed1989

Structural changes in ageing and dementia of Alzheimer's type with special reference to recent etiologic and therapeutic theories.

On the basis of a large material of organic dementia, accumulated during a 20 year long prospective study, certain basic structural changes in dementia, mainly of Alzheimer's type (DAT) viz. the topography of lesions, the amyloid angiopathy and white matter changes are discussed with respect to their relevance for modern etiologic and pathogenetic theories and implications for the clinical picture and treatment in DAT. The topographic pattern and its evolution appears to be a relevant basis for the symptomatology and the picture shown by PET and regional cerebral blood flow studies. It lends some support to theories implicating the spread of a causative agent via olfactory pathways. The amyloid depositions, particularly those in the vessels present, both with regard to amount and topography, features which to some extent validate the modern etiological gene theories but which in other respects lend little or no support to the etiologic or pathogenetic importance ascribed to amyloid. The white matter changes, common in DAT and of an incomplete infarction type, may blur the DAT clinic and also serve to block axonal transport through the white matter and cause dysfunction or death of neurons dependent upon routes involved. It might thus influence therapeutic measures such as administration of transmitter substitutes or their precursors and the outgrowth or efficacy of transplanted cholinergic replacement neurons.

Aging↗
PubMed1988

Limbic encephalitis after inhalation of a murine coronavirus.

The spread of a neurotropic coronavirus, mouse hepatitis virus strain A59, in the mouse central nervous system was studied after intranasal inoculation. Mouse hepatitis virus strain A59 spread during the 3- to 5-day postinoculation period, through the olfactory pathway into the limbic system. Coronavirus particles were detected in the limbic system by electron microscopy. The combination of temporal propagation through an anatomical-physiological central nervous system pathway and anatomical restriction of viral infection suggests that specific interneuronal transport is important in spread of the virus. This experimental system may represent a model for diseases associated with human coronaviruses (common cold viruses) and/or the human limbic system.

Administration, Intranasal↗