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Calmodulin, calbindin-D28k, calretinin and neurocalcin in rat olfactory bulb during postnatal development.

Odorant stimulation of receptor cells results in a calcium influx that activates the transduction pathway. The olfactory neurons extend axons to the olfactory bulb where they synapse onto mitral cells. Ca(2+)-acceptors also may participate in subsequent processing of olfactory information. The present study describes the distribution of calmodulin, calretinin, calbindin-D28k and neurocalcin during rat main olfactory bulb development. From postnatal day 1 (P1) we observed in the olfactory nerve layer a thin external bundle containing calbindin and calretinin whereas calmodulin was present in a large internal bundle. In tufted cells, neurocalcin immunoreactivity was detected at P10 and increased until P20. In mitral cells calmodulin was intensively immunoreactive at P1 but decreased during development to disappear at adulthood whereas calretinin was weakly labelled at P1 but raised in intensity until P20. In granule cells calbindin-D28k and calretinin were detected from P1. Giant neurons were positive for both calretinin and calbindin-D28k from postnatal day 20.

Aging↗

The development of the retinopetal nucleus olfacto-retinalis of two cichlid fish as revealed by horseradish peroxidase.

Adult patterns and the development of the nucleus of origin of centrifugal innervation of the retina, the nucleus olfacto-retinalis (NOR), were studied with horseradish peroxidase in 2 cichlid fish species. In the adults large and small cells within the nuclear boundaries can be distinguished by their cytoarchitecture and their HRP-labelling. The NOR is already formed at hatching (5.5 days post-spawning) but cannot be filled by HRP injections into one eye until 2 days later. The number of labelled neurons increases steadily until adult cell density is reached. Later larval stages show that the NOR neurons also increase in size. The two cell types found in the adult can first be distinguished at around 30 days post-spawning. Early unilateral enucleation reduces the density of the small cells in the contralateral NOR. In spite of different environmental constraints on the growth of the larvae, the NOR develops in a similar way in both species but always somewhat later in the substrate-spawner than in the mouth-brooder. The centrifugal innervation of bird (isthmo-optic nucleus, ION) and fish (NOR) retinae starts at comparable developmental stages of the retina, but no cell death as found in the developing ION in birds occurs in the developing NOR in fish. It is suggested that this is due to the constant adjustment of the NOR to the ever increasing cell numbers in the fish retina. The NOR is thus the only known centrifugally projecting nucleus in vertebrates which lacks extensive degenerating patterns during early development. The known LH-RH immunoreactivity, the two cell types, the early development, and the projection to the retina of the NOR in cichlid fish resemble closely characteristics of the ganglion of the terminalis nerve of other piscine species.

Animals↗

Luteinizing hormone-releasing hormone in the pigeon terminal nerve and olfactory bulb.

The presence of a terminal nerve in the avian brain has recently been reported. As the terminal nerve in other classes of vertebrates contains luteinizing hormone-releasing hormone (LHRH), we used immunocytochemistry to determine whether the pigeon terminal nerve also contained LHRH. We found LHRH-immunoreactivity in the olfactory nerve and in the olfactory bulb. The distribution of LHRH neurons was similar to the LHRH neuronal migration pathway during development.

Animals↗

The telencephalon of the sea catfish Galeichthys felis.

The sea catfish is a relatively abundant teleost fish. Its placement on the phylogenetic scale remains in question, although its brain resembles grossly those of some of the other teleosts which also possess pedunculated olfactory bulbs. The forebrain of Galeichthys felis consists of two hemispheres which lack lateral ventricles. They are joined at the midline by a thin membrane ventromedially and by the hippocampal and anterior commissures. The telencephalic hemispheres are overlaid by a single, ventrolaterally attached membrane which is continuous rostrally with the roofs of the olfactory ventricles. Six basic nuclear regions are evident in the telencephalon of the sea catfish: a dorsomedial, a ventromedial, a ventral, a lateral, a dorsal and a central. Dorsomedially, the primordial hippocampal formation is divided into an anterior continuation, a primordial dentate gyrus, a primordial cornu ammonis and a primordial subiculum. Ventromedially, the precommissural septum consists of the medial septal nucleus (pars dorsalis and pars ventralis), the lateral septal nucleus and the nuclei of the hippocampal and anterior commissure. Ventrally, the medial and the lateral zones and the medial island constitute the tuberculum olfactorium. The primordial general pallium comprises the dorsal area. Laterally, the primordial piriform cortex and the prepiriform region overlie the relatively large primordial amygdaloid complex, which includes an anterior anygdaloid nucleus, a primordial corticomedial amygdaloid nucleus and a primordial basolateral amygdaloid nucleus. The hyperstriatum, the neostriatum, and paleostriatum augmentatum and the paleostriatum primitivum constitute the central region. Basic fiber systems in Galeichthys felis which are homologous to those of higher vertebrates include the medial and the lateral olfactory tracts, the fornix, the medial and the lateral forebrain bundles, the stria medullaris pathways and the stria terminalis. In spite of the lack of lateral telencephalic ventricles in this form, nuclear areas were defined which, on the basis of topography, cellular morphology and fiber pathways, were homologized with the six basic regions found in the forebrain of higher vertebrates. The basic pattern of the fiber pathways present in the sea catfish corresponds to that found in the other submammalian vertebrates.

Amygdala↗

Modulation of odor-induced increases in [Ca(2+)](i) by inhibitors of protein kinases A and C in rat and human olfactory receptor neurons.

Protein kinases A and C have been postulated to exert multiple effects on different elements of signal transduction pathways in olfactory receptor neurons. However, little is known about the modulation of olfactory responses by protein kinases in intact olfactory receptor neurons. To further elucidate the details of the modulation of odorant responsiveness by these protein kinases, we investigated the action of two protein kinase inhibitors: H89, an inhibitor of protein kinase A, and N-myristoylated EGF receptor, an inhibitor of protein kinase C, on odorant responsiveness in intact olfactory neurons. We isolated individual olfactory neurons from the adult human and rat olfactory epithelium and measured responses of the isolated cells to odorants or biochemical activators that have been shown to initiate cyclic AMP or inositol 1,4,5-trisphospate production in biochemical preparations. We employed calcium imaging techniques to measure odor-elicited changes in intracellular calcium that occur over several seconds. In human olfactory receptor neurons, the protein kinase A and C inhibitors affected the responses to different sets of odorants. In rats, however, the protein kinase C inhibitor affected responses to all odorants, while the protein kinase A inhibitor had no effect. In both species, the effect of inhibition of protein kinases was to enhance the elevation and block termination of intracellular calcium levels elicited by odorants. Our results show that protein kinases A and C may modulate odorant responses of olfactory neurons by regulating calcium fluxes that occur several seconds after odorant stimulation. The effects of protein kinase C inhibition are different in rat and human olfactory neurons, indicating that species differences are an important consideration when applying data from animal studies to apply to humans.

Adolescent↗

Odorant inhibition of the olfactory cyclic nucleotide-gated channel with a native molecular assembly.

Human olfaction comprises the opposing actions of excitation and inhibition triggered by odorant molecules. In olfactory receptor neurons, odorant molecules not only trigger a G-protein-coupled signaling cascade but also generate various mechanisms to fine tune the odorant-induced current, including a low-selective odorant inhibition of the olfactory signal. This wide-range olfactory inhibition has been suggested to be at the level of ion channels, but definitive evidence is not available. Here, we report that the cyclic nucleotide-gated (CNG) cation channel, which is a key element that converts odorant stimuli into electrical signals, is inhibited by structurally unrelated odorants, consistent with the expression of wide-range olfactory inhibition. Interestingly, the inhibitory effect was small in the homo-oligomeric CNG channel composed only of the principal channel subunit, CNGA2, but became larger in channels consisting of multiple types of subunits. However, even in the channel containing all native subunits, the potency of the suppression on the cloned CNG channel appeared to be smaller than that previously shown in native olfactory neurons. Nonetheless, our results further showed that odorant suppressions are small in native neurons if the subsequent molecular steps mediated by Ca(2+) are removed. Thus, the present work also suggests that CNG channels switch on and off the olfactory signaling pathway, and that the on and off signals may both be amplified by the subsequent olfactory signaling steps.

Animals↗

Influence of nasal trigeminal stimuli on olfactory sensitivity.

In the nose, the capacity to detect and react to volatile chemicals is mediated by two separate but interrelated sensory pathways, the olfactory and trigeminal systems. Because most chemosensory stimulants, at sufficient concentration, produce both olfactory and trigeminal sensations (i.e., stinging, burning or pungent), it is relevant to seek how these anatomically distinct systems could interact. This study was designed to evaluate by psychophysical measurements the modifications of the olfactory sensitivity of 20 subjects to phenyl ethyl alcohol (PEA) and butanol (BUT), after trigeminal stimulation with allyl isothiocyanate (AIC). Thresholds obtained in two separate sessions, one with and the other without previous trigeminal stimulation, were compared using a two-alternative forced-choice procedure, with a classical ascending concentrations method. The results showed that, whatever the odorant (PEA or BUT), AIC trigeminal activation produced a decrease in the olfactory thresholds, corresponding to an increase in olfactory sensitivity. These data confirm that in physiological conditions the trigeminal system modulates the activity of olfactory receptor cells but do not exclude the possibility of a central modulation of olfactory information by trigeminal stimuli. These findings are discussed in terms of methodological and physiological conditions.

Adult↗

Vagus nerve stimulation modifies the electrical activity of the olfactory bulb.

Evoked potential and unit activity recording techniques were used to study the effects of the vagus nerve stimulation on the olfactory bulb. A biphasic potential was evoked in the olfactory bulb by a single pulse delivered to the vagus nerve. Half of the neurons studied decreased discharge frequency after single pulse or train stimulation. The interval during which neurons ceased activity corresponded to the duration of the negative wave of the evoked potential. Responsive neurons were marked with horseradish peroxidase applied iontophoretically. Responsive neurons were located in the periglomerular layer of the olfactory bulb. These results suggest the existence of a vagus nerve-olfactory bulb pathway. The functional significance of this pathway is discussed.

Afferent Pathways↗

Convergence of olfactory and gustatory connections onto the endopiriform nucleus in the rat.

Electrical and optical recordings were made from slice preparations including the piriform and gustatory cortices. Electrical stimulation of the gustatory cortex evoked a characteristic field potential in the endopiriform nucleus. A field potential was induced in the endopiriform nucleus by stimulation of the piriform cortex. Voltage-sensitive dye studies showed that stimulation of the piriform cortex induced signal propagation from the piriform cortex to endopiriform nucleus, whereas stimulation of the gustatory cortex did the same from the gustatory cortex to endopiriform nucleus via the agranular division of the insular cortex. After stimulation of the endopiriform nucleus, optical signals propagated not only to the piriform cortex but also to the gustatory cortex via the agranular division of the insular cortex. The olfactory and gustatory pathways appeared to be reciprocally connected. Unit recordings indicated that olfactory and gustatory activity converged onto a single neuron of the endopiriform nucleus. It is suggested that the cortical integration of olfactory and gustatory information could modulate mechanisms involved in food selection and emotional reactions relating to the chemical senses.

Animals↗

The indusium griseum in the mouse: architecture, Timm's histochemistry and some afferent connections.

The Indusium griseum (IG) is an enigmatic cortical field classically felt to be a part of the hippocampus (HC). In the mouse, IG lies just dorsal to the corpus callosum at the base of the anterior half of cingulate cortex. In coronal sections the field is small but constitutes a fairly long rostro-caudal strip. The connections of the IG are poorly understood. The Timm's staining pattern of the IG is reminiscent of a mini-dentate gyrus (DG) comprising a layer of granule cells with two bands of staining in the molecular layer. In the DG there are three bands which correspond to inputs from the lateral and medial entorhinal area (LEA and MEA) and the ipsi- and contralateral association systems. Using anterograde transport of HRP we have found that the LEA and MEA also terminate in the molecular layer of the IG. This suggests that the IG is a displaced portion of the DG. The olfactory system is known to have a strong indirect influence on the HC via primary and secondary bulbar projections to the LEA. Wheat germ agglutinin-HRP injections confined to the main olfactory bulb (MOB) show a direct projection from the MOB to IG. Both the olfactory bulb itself and retrobulbar structures such as the piriform cortex (PC) convey olfactory information to the LEA; the LEA supplies a major input to the DG. Our results suggest that there is a more direct pathway whereby olfactory information may influence a cortical region, IG, whose histochemistry and direct afferents from the entorhinal cortex suggest that it is part of or closely related to the DG. Thus, IG may represent a phylogenetically old olfacto-recipient outpost of the hippocampus.

Afferent Pathways↗