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Results for “Olfactory Receptor Neurons”

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At least 19 recordsLinked to original sources

PubMed2001

IP3-gated channels and their occurrence relative to CNG channels in the soma and dendritic knob of rat olfactory receptor neurons.

Olfactory receptor neurons respond to odorants with G protein-mediated increases in the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) and/or inositol-1,4,5-trisphosphate (IP3). This study provides evidence that both second messengers can directly activate distinct ion channels in excised inside-out patches from the dendritic knob and soma membrane of rat olfactory receptor neurons (ORNs). The IP3-gated channels in the dendritic knob and soma membranes could be classified into two types, with conductances of 40 +/- 7 pS (n = 5) and 14 +/- 3 pS (n = 4), with the former having longer open dwell times. Estimated values of the densities of both channels from the same inside-out membrane patches were very much smaller for IP3-gated than for CNG channels. For example, in the dendritic knob membrane there were about 1000 CNG channels x microm(-2) compared to about 85 IP3-gated channels x microm(-2). Furthermore, only about 36% of the dendritic knob patches responded to IP3, whereas 83% of the same patches responded to cAMP. In the soma, both channel densities were lower, with the CNG channel density again being larger ( approximately 57 channels x microm(-2)) than that of the IP3-gated channels ( approximately 13 channels x microm(-2)), with again a much smaller fraction of patches responding to IP3 than to cAMP. These results were consistent with other evidence suggesting that the cAMP-pathway dominates the IP3 pathway in mammalian olfactory transduction.

Animals↗

PubMed1987

Patch-clamp studies of isolated mouse olfactory receptor neurons.

Olfactory receptor neurons isolated from embryonic, neonatal, and adult mice were studied using the patch-clamp technique. Several distinct types of ion channels were characterized in patches of membrane from the neuronal soma and the dendritic knob of receptor neurons, including a 130-pS Ca++-activated K+ channel with voltage-dependent kinetics, an 80-pS Ca++-activated K+ channel with voltage-insensitive kinetics, a 25-pS K+ channel with properties similar to inward rectifiers, and a 40-pS K+ channel that was activated and then inactivated by rapid depolarization. Evidence of large-conductance (greater than 200 pS) Cl- channels, which were Ca++ insensitive and increasingly active at depolarizing membrane potentials, and voltage-activated Ca++ channels (16 pS) was also obtained. From K+ channel activity recorded from cell-attached patches, the intracellular [Ca++] was inferred to be below 0.1 microM, and the membrane potential was inferred to be approximately -50 mV. The receptor neurons had high input resistances, and action potentials could be elicited by picoampere amounts of depolarizing current. The receptor neurons responded to applied odorant molecules and to forskolin with increases in membrane conductance. These results provide a description of the membrane properties of olfactory receptor neurons and a basis for understanding their electrical activity and response to odorants.

Animals↗

PubMed2005

Evidence for multiple calcium response mechanisms in mammalian olfactory receptor neurons.

Olfactory receptor neurons employ a diversity of signaling mechanisms for transducing and encoding odorant information. The simultaneous activation of subsets of receptor neurons provides a complex pattern of activation in the olfactory bulb that allows for the rapid discrimination of odorant mixtures. While some transduction elements are conserved among many species, some species-specificity occurs in certain features that may relate to their particular physiology and ecological niche. However, studies of olfactory transduction have been limited to a relatively small number of vertebrate and invertebrate species. To better understand the diversity and evolution of olfactory transduction mechanisms, we studied stimulus-elicited calcium fluxes in olfactory neurons from a previously unstudied mammalian species, the domestic cat. Isolated cells from cat olfactory epithelium were stimulated with odorant mixtures and biochemical agents, and cell responses were measured with calcium imaging techniques. Odorants elicited either increases or decreases in intracellular calcium; odorant-induced calcium increases were mediated either by calcium fluxes through the cell membrane or by mobilization of intracellular stores. Individual cells could employ multiple signaling mechanisms to mediate responses to different odorants. The physiological features of these olfactory neurons suggest greater complexity than previously recognized in the role of peripheral neurons in encoding complex odor stimuli. The investigation of novel and unstudied species is important for understanding the mechanisms of odorant signaling that apply to the olfactory system in general and suggests both broadly conserved and species-specific evolutionary adaptations.

Animals↗

PubMed1998

Primary culture of adult mouse olfactory receptor neurons.

Olfactory receptor neurons (ORNs) are unique because they can be replaced by stem cells throughout life. Previous studies have demonstrated that adult mouse olfactory epithelium (OE) injured by exposure to ZnSO4 through nasal irrigation can stimulate stem cell mitotic activity in situ, which continues when placed in culture. We report on an improved ZnSO4 delivery method, mist inhalation, which produces more consistent and greater yields of OE cells. Cultures established following this method contained bipolar, nest, fusiform, and giant cells. The bipolar cells usually underwent asymmetric process development. Some bipolar cells reacted positively to neuron-specific antibodies and were immunonegative for keratin and glia-specific proteins, suggesting that they were ORNs. Those that were negative for the neuron-specific proteins may represent either neuron progenitors or olfactory ensheathing cells. The fusiform cells were relatively small and undifferentiated, exposure to brain-derived neurotrophic factor resulted in their decrease and an increase in bipolar cells. Therefore, they might be the stem cells. The nest cells had morphological characteristics of epithelia and bound keratin antibodies. The giant cells had the morphology of epithelial cells but were negative for keratin; they may represent a unique cell population induced by the ZnSO4. These results indicate that the major cell types of intact OE are present in our cultures, and each retains characteristics found in situ. The mist inhalation method provides an in vitro population of adult mitotically active neurons for study.

Administration, Inhalation↗

PubMed1994

Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons.

Olfactory receptor neurons depolarize in response to odorant stimulation of their sensory cilia. One transduction mechanism involves a G-protein-mediated increase in adenylate cyclase activity, raising the internal cyclic AMP concentration to open a cyclic nucleotide-activated cation channel on the plasma membrane. An influx of Ca2+ through this channel, which is permeable to both monovalent and divalent cations, triggers olfactory adaptation. Previous work has indicated that at least part of this Ca(2+)-mediated adaptation resides in the channel itself, but the mechanism remains unclear and controversial. Here we use the cloned channel from rat expressed in a cell line and the native channel from rat olfactory receptor cells to show that Ca2+ reduces the apparent affinity of the channel for cAMP by up to 20-fold in the presence of calmodulin, an abundant protein in olfactory cilia. This decrease in apparent affinity appears to involve a direct interaction between Ca(2+)-calmodulin and the channel, and it can reduce the activation of the channel by cAMP by up to a few hundred-fold, suggesting that it may be a key component of the Ca(2+)-triggered olfactory adaptation.

Animals↗

PubMed1991

Differential spatial and temporal expression of two type III intermediate filament proteins in olfactory receptor neurons.

Olfactory receptor neurons (ORNs) do not express the typical neuronal intermediate filament proteins (IFPs), the neurofilament triplet proteins. Immunocytochemical evidence shows that ORNs coexpress vimentin and peripherin but distribute them differently. Specifically, ORNs contain vimentin in dendrites, cell bodies, and axons, but not in terminals in glomeruli; peripherin is present in axons, but excluded from dendrites, cell bodies, and terminal glomeruli. In adult rats, ORN axon fascicles are variably stained with antisera for peripherin; in juvenile rats, staining of fascicles is uniform. Staining with antibody to vimentin is uniform in both adult and juvenile ORN axon fascicles. The unusual pattern of IFP expression and intracellular sorting may have implications for the unique plastic and regenerative capacities of these neurons.

Age Factors↗

PubMed2000

Functional synapse formation between rat olfactory receptor neurons and olfactory bulb neurons in vitro.

To explore the mechanism of the synapse formation between olfactory receptor neurons and neurons in the olfactory bulb, blocks of olfactory epithelium and slices of olfactory bulb were cocultured by a modified slice culture method. After 4 days in culture, neuron specific fibers from the olfactory epithelium block extending to the olfactory bulb slice were observed. After approximately 20 days in culture, application of forskolin, which induces excitatory responses in olfactory receptor neurons, to the epithelium induced inward current responses in olfactory bulb neurons under the voltage clamp conditions, indicating that functional synapses between olfactory receptor neurons and olfactory bulb neurons had been established in vitro conditions.

Animals↗

PubMed1989

Odor-induced membrane currents in vertebrate-olfactory receptor neurons.

In olfactory receptor neurons, odor molecules cause a depolarization that leads to action potential generation. Underlying the depolarization is an ionic current that is the earliest electrical event in the transduction process. In two preparations, olfactory receptor neurons were voltage-clamped and stimulated with odors and this generator current was measured. In addition, a method was developed to estimate the time course and absolute concentration of odorants delivered to the receptor sites. With this method, olfactory neurons were found to have relatively high stimulus thresholds, steep dose-response relations, long latencies, and an apparent requirement for cooperativity at one or more steps in the pathway from odorant binding to activation of the generator current.

Ambystoma↗

PubMed1998

Betaine activates a hyperpolarizing chloride conductance in squid olfactory receptor neurons.

Isolated olfactory receptor neurons from the squid Lolliguncula brevis respond to betaine, a repellent odorant, with hyperpolarizing receptor potentials. Using perforated-patch techniques, we determined that the hyperpolarizing conductance was selective for Cl- and could be reversibly blocked by the Cl- channel blockers 4-acetamido-4'-isothio-cyanatistilbene-2,2'disulfonic acid and niflumic acid. Gramicidin-patch recordings revealed that [Cl-]i in squid olfactory receptor neurons is normally very low compared to vertebrate olfactory receptor neurons, and that activating a Cl- conductance would hyperpolarize the cell in vivo. The lack of dependence on internal or external K+ or Na+ ruled out the possibility that the Cl- conductance was generated by a cation-dependent cotransporter or pump. Common G-protein-dependent signalling pathways, including phospholipase C, arachidonic acid, and cyclic nucleotides, do not appear to be involved. Ca2+ imaging experiments showed that betaine did not affect [Ca2+]i, suggesting that the Cl- current is not Ca2+ dependent. Our findings represent the first report of an odorant-activated, hyperpolarizing chloride conductance in olfactory receptor neurons.

Animals↗

PubMed1991

Two types of increases in free Ca2+ evoked by odor in isolated frog olfactory receptor neurons.

Olfactory transduction involves second messenger-related enzymes and cAMP-gated, K+ and Ca2+ channels, which are known to be regulated by Ca2+. We report here that cytosolic free Ca2+ concentration ([Ca2+]i) in olfactory receptor neuron was increased by odorants or forskolin and Ca2+ influx contributed to the adaptation. The increases in [Ca2+]i were below two to three-fold of resting level and transient for 26 s (mean value, n = 18). The increases were due to two pathways: Ca2+ influx and release. The slow increases in [Ca2+]i by forskolin resembled those by citralva. It was suggested that the responses to citralva were accompanied by increases in intracellular cAMP and Ca2+ influx or release leading to transient increases in [Ca2+]i.

Animals↗

PubMed1995

G-protein subunits expressed in catfish olfactory receptor neurons.

Olfactory signal transduction in a number of species has been shown to be mediated by heterotrimeric GTP-binding proteins (G-proteins). The expression of different G-proteins in channel catfish (Ictalurus punctatus) olfactory epithelium was investigated using antibodies to both the alpha and beta subunits of G-proteins. Based on Western blotting and immunohistochemical data, the following G-protein subunits were identified in the olfactory epithelium: Gs/G(olf), Gi1, Gi2, Gq and G beta. Immunohistochemical results indicated that all of these G-proteins, encompassing three G-protein subfamilies, were expressed in the dendrites and cilia of olfactory receptor neurons. These findings suggest that different G-protein subunits may mediate multiple signal transduction pathways in the catfish olfactory system, i.e. G(olf)/Gs, may mediate odorant activation of adenylyl cyclase while Gi and G beta may mediate odorant activation of phospholipase C.

Amino Acid Sequence↗

PubMed1999

Transient and persistent tetrodotoxin-sensitive sodium currents in squid olfactory receptor neurons.

Squid olfactory receptor neurons are primary bipolar sensory neurons capable of transducing water-born odorant signals into electrical impulses that are transmitted to the brain. In this study, we have identified and characterized the macroscopic properties of voltage-gated Na+ channels in olfactory receptor neurons from the squid Lolliguncula brevis. Using whole-cell voltage-clamp techniques, we found that the voltage-gated Na+ channels were tetrodotoxin sensitive and had current densities ranging from 5 to 169 pA pF-1. Analyses of the voltage dependence and kinetics revealed interesting differences from voltage-gated Na+ channels in olfactory receptor neurons from other species; the voltage of half-inactivation was shifted to the right and the voltage of half-activation was shifted to the left such that a "window-current" occurred, where 10-18% of the Na+ channels activated and did not inactivate at potentials near action potential threshold. Our findings suggest that in squid olfactory neurons, a subset of voltage-gated Na+ channels may play a role in generating a pacemaker-type current for setting the tonic levels of electrical activity required for transmission of hyperpolarizing odor responses to the brain.

Animals↗

PubMed2005

Specificity of odorant-evoked inhibition in lobster olfactory receptor neurons.

Lobster olfactory receptor neurons, like those of many animals, use two modes of olfactory signaling, excitation and inhibition to code olfactory information. Inhibition appears to act through two distinct ionic mechanisms. Here we show that neither ionic mechanism is odor-specific, providing further support for the emerging understanding that there are no inhibitory odorants per se, but rather that the action of a particular odorant is inherent in the olfactory receptor cell on which an odorant acts.

Animals↗

PubMed1994

The cyclic nucleotide gated channel of olfactory receptor neurons.

Olfactory transduction proceeds through a G-protein coupled cascade that produces the ubiquitous second messenger cyclic AMP. The cyclic AMP causes a change in membrane potential by acting directly on an ion channel that allows cations to flow into the cell. This ion channel is one of a new family of ion channels that are activated by intracellular cyclic nucleotides. However, even though they are activated by binding a ligand their amino acid structure shows that they share a common ancestry with voltage activated channels, especially voltage dependent Ca2+ channels. In olfactory neurons these channels perform a critical role in the transduction of chemical information in the environment into changes in membrane electrical properties that are transmitted to higher order processing centers in the brain.

Animals↗

PubMed2001

Phosphorylation of voltage-gated ion channels in rat olfactory receptor neurons.

In olfactory receptor neurons (ORNs), ligand-odorant receptor interactions cause G protein-mediated activation of adenylate cyclase and a subsequent increase in concentration of the intracellular messenger cAMP. Odorant-evoked elevation in cAMP is thought to directly activate a cation-selective cyclic nucleotide-gated channel, which causes external Ca2+ influx, leading to membrane depolarization and the generation of action potentials. Our data show that in freshly dissociated rat ORNs, odorant-induced elevation in cAMP also activates cAMP-dependent protein kinase (PKA), which is then able to phosphorylate various protein targets in the olfactory signal transduction pathway, specifically voltage-gated sodium and calcium channels. The presence of PKI (PKA inhibitor peptide) blocked the modulatory action of cAMP on voltage-gated ion channels. By modulating the input/output properties of the sensory neurons, this mechanism could take part in the complex adaptation process in odorant perception. In addition, we found modulation of voltage-gated sodium and calcium channel currents by 5-hydroxytryptamine and the dopamine D1 receptor agonist SKF 38393. These findings suggest that in situ ORNs might also be a target for efferent modulation.

Animals↗

PubMed2005

Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis.

Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis after target removal (bulbectomy), in which axonal caspase-9 and caspase-3 activation leads to terminal apoptosis in ORN soma of the olfactory epithelium. Here, we show that caspase-8 can act as an initiator of ORN apoptosis after bulbectomy and also after synaptic instability is induced by NMDA-mediated excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and caspase-3 are sequentially activated within ORN presynaptic terminals, and caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is transported retrogradely, preceding axonal caspase-3 activation and apoptosis of ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death. Caspase-8 activation and retrograde transport after NMDA lesion is similarly reduced in mice null for p75, the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs thus involves a novel mechanism that used p75 in the local activation of caspase-8. Once caspase-8 is maximally activated in the presynaptic terminal, it is transported retrogradely by the motor complex dynactin/dynein, a process that can be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage and the loss of olfactory bulb target neurons.

Acetylcholine↗

PubMed1981

Ultrastructural changes in olfactory receptor neurons following olfactory nerve section.

Unilateral olfactory nerve section was performed in the salamander, Ambystoma tigrinum. An ultrastructural study was performed to investigate the changes occurring during degeneration and replacement of the mature olfactory receptor neurons. Experimental and contralateral control tissues were examined following postoperative survival periods ranging from 12 hours to 90 days. Normal bipolar receptor neurons have a fusiform cell body containing a thin rim of cytoplasm and an ovoid nucleus with a characteristic "checkerboard" chromatin pattern. A single apical dendrite projects to the surface of the epithelium, where numerous cilia extend from its apex into the overlying mucus. A single, unmyelinated, unbranching axon originates at the basal pole of the cell. After nerve section, retrograde degeneration of the mature neurons occurs. Early degenerative changes include pronounced condensation of the nuclear chromatin, increased number of nuclear membrane infoldings, and dilation of the space between the membranes of the nuclear envelope. At a later stage, the cytoplasm of the cell increases in volume and its organelle systems break down, resulting in accumulation of various forms of cell inclusions. Subsequently, proliferation of cells in the basal region of the epithelium occurs. Between 3 week and 2 months following nerve section, these cells differentiate into mature neurons. By 3 months, neurons within the epithelium have resumed their normal ultrastructure. Correlation of the time course of the ultrastructural changes with previously reported neurophysiological studies indicates that neuronal activity of the epithelium is dependent upon the presence of fully differentiated olfactory receptor neurons.

Ambystoma↗

PubMed1992

Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels in olfactory receptor neurons.

In olfactory receptor neurons, odorants stimulate production of cAMP, which directly activates cyclic nucleotide-gated (CNG) channels. Olfactory adaptation is thought to result from a rise in intracellular Ca2+. To determine whether inhibition of CNG channels plays a role in adaptation, we have investigated the action of Ca2+ on these channels in inside-out "macro" patches from the dendrite and cilia of catfish olfactory neurons. Internal Ca2+, with a K1/2 of 3 microM, profoundly inhibits CNG channels by shifting the dose-response relationship to higher cAMP levels without altering the maximal response. The inhibition does not appear to result from a direct interaction of Ca2+ with the CNG channel. Thus, the inhibition washes out after excision of the inside-out patch, and Ca2+ does not inhibit the cloned catfish CNG channel expressed in Xenopus oocytes. Hence we propose that a regulatory Ca(2+)-binding protein, distinct from the CNG channel, controls the gain of signal transduction and contributes to olfactory adaptation by decreasing the sensitivity of the CNG channel to cAMP.

Animals↗