Abstract: Impaired olfaction occurs in patients with idiopathic Parkinson's disease (PD), and Lewy bodies have been found in the olfactory bulb and tract. We now confirm the latter finding and show that this presence of Lewy bodies is associated with significant neuronal loss. A quantitative study of the anterior olfactory nucleus (AON) was performed in tissue obtained postmortem from seven patients with PD and seven age-matched controls. Neuronal loss was seen in the PD bulb and tracts (p < 0.01), and a strong correlation of neuronal loss with disease duration was detected (R = -0.87). The presence of Lewy bodies was confirmed with immunocytochemical staining for ubiquitin in all the PD cases.

Abstract: Odours play a very important role in the life of insects belonging to the order Lepidoptera. In the present paper, a review is given of the current knowledge of morphology, development and function of the olfactory system in larval and adult moths and butterflies. Research regarding both the antennal and accessory olfactory pathways, as well as both the pheromone and the host odour detecting systems, is reviewed.

Abstract: Introduction - Olfaction is markedly impaired in patients with idiopathic Parkinson's disease (IPD). This deficit contrasts with reports of preserved or only mildly reduced olfaction in patients with atypical parkinsonism. However, the sensitivity and specificity of olfactory function testing in the differential diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory function in patients with corticobasal degeneration (CBD) is unknown. Material and methods - Using the University of Pennsylvania Smell Identification Test (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in patients with IPD as well as other parkinsonian syndromes including CBD and progressive supranuclear palsy (PSP). Results - UPSIT scores in 118 patients with IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well. as in 123 healthy control subjects revealed a marked impairment in the IPD group in contrast to mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity of 85% in differentiating IPD from atypical parkinsonism. Conclusions - These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Abstract: Intraspecific and interspecific communication and recognition depend on olfaction in widely diverse species of animals. Olfaction, an ancient sensory modality, is based on principles of neural organization and function that appear to be remarkably similar throughout the zoosphere. Thus, the "primitives" of olfactory stimuli that determine the input information of olfaction, the kinds of "molecular images" formed at various levels in the olfactory pathway, and the cellular mechanisms that underlie olfactory information processing are comparable in invertebrates and vertebrates alike. A case in point is the male-specific olfactory subsystem in moths, which is specialized to detect and analyze the qualitative, quantitative, and temporal features of the con-specific females' sex-pheromonal chemical signal. This olfactory subsystem can be viewed, and is here presented, as a model in which common principles of organization and function of olfactory systems in general are exaggerated to serve the requirements of a chemical communication system that is crucial for reproductive success.

Abstract: This study used Fos immunocytochemistry to locate neurons within the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBNST) that are tightly associated with the performance of maternal behavior in postpartum rats. In the first experiment, a high degree of Fos activation was observed in these regions if females were allowed to interact fully with pups, but not if they could receive only olfactory, visual, and auditory inputs from pups. The second experiment found that olfactory bulbectomy combined with thelectomy did not eliminate Fos expression in the MPOA and VBNST of females displaying maternal behavior. These Fos-expressing neurons may represent efferent neurons essential for the performance of maternal behavior.

Abstract: General Methods in Chemosensory Research Euthanasia, I. Ramirez Collection of Taste Tissue from Fish and Amphibians, J. H. Teeter Collection of Taste Tissue from Mammals, A. I. Spielman and J. G. Brand Insects: Isolation of Olfactory Sensilla and Collection of Sensillum Lymph, G. Ziegelberger Surgical Anatomy of Olfactory Organ and Tissue Collection Methods in Vertebrates, T. Kurahashi and D. Restrepo Collection of Human Olfactory Tissue, L. D. Lowry and E. A. Pribitkin Surgical Removal of the Vomeronasal Organ and Its Verification, C. J. Wysocki and L. M. Wysocki Denervation and Reinnervation of the Tongue, B. Oakley The Lingual Slice Preparation, Isolated Taste Cells, and Dye Injections in Mudpuppy, A. Bigiani, D. A. Ewald, and S. D. Roper Cell Dissociation Methods for Patch Clamp Electrophysiological Studies of Vertebrate Olfactory Receptor Neurons, A. H. Kahn and S. Firestein Tissue Culture of Rat Taste Buds, C. Ruiz, M. McPheeters, and S. C. Kinnamon Olfactory Receptor Neuronal Cultures, G. V. Ronnett Methods for Airborne and Aqueous Stimulus Delivery in Olfactory Research, J. S. Kauer and S. Firestein Imaging Methods in Chemosensory Research Videomicroscopy and Image Processing, I. J. Miller and S. L. Hayes Transmission Electron Microscopy of Gustatory Epithelium, H. H. Crowley and J. C. Kinnamon Scanning and Transmission Electron Microscopy of Olfactory Epithelia, B. Ph. M. Menco Analysis of Taste Bud Ultrastructure by Serial Sectioning and Three-Dimensional Reconstruction, S. M. Royer and J. C. Kinnamon Immunohistochemistry, C. DellaCorte IP3 Autoradiography of Taste Receptor Cells, P. A. Hwang In Situ Hybridization, H. Schmale and M. Behrens Biochemical Methods in Chemosensory Research Membrane Preparation and Subcellular Fractionation, D. L. Kalinoski Preparation of Olfactory Cilia, R. R. H. Anholt The Use of the Spiny Lobster as a Tool for the Study of Chemosensory Biochemistry, H. G. Trapido-Rosenthal Receptor Binding and Solubilization, D. L. Kalinoski Western Blotting, R. Bruch and Fe. C. Abogadie Approaches for Monitoring Rapid Kinetics of Second Messenger Signaling, E. Tareilus, I. Boekhoff, A.I. Spielman, and H. Breer Second Messenger Assays, A. I. Spielman, H. Nagai, G. Sunavala, M. Dasso, T. Huque, and J. G. Brand Electrophysiological and Biophysical Methods in Chemosensory Research General Methods Reconstitution of Chemoreceptor Proteins in Planar Lipid Bilayers, A. M. Feigin, M. Zviman, and J. H. Teeter Data Acquisition in Electrophysiology, V. E. Dionne Whole Nerve and Single Unit Recordings Taste Nerve Recording from a Voltage-Clamped Receptive Field, J. A. DeSimone, G. Heck, and Q. Ye Whole Nerve and Single Fiber Recordings in Frog, T. Miyamoto and T. Sato Single Unit Electrophysiological Recordings from Crustacean Chemoreceptor Neurons, C. D. Derby Olfactory and Taste Recordings in Fish, J. Caprio Taste Nerve Recordings in Rodents, M. E. Frank Trigeminal Nerve Recordings in Rodents, B. P. Bryant Whole Nerve and Single Fiber Recordings in Non-Human Primates, G. Hellekant and T. W. Roberts Electrophysiology of the Vomeronasal Organ and Accessory Olfactory System, M. Meredith Patch-Clamping Patch-Clamping of Taste Cells in the Mudpuppy, T. A. Cummings and S. C. Kinnamon Patch-Clamping Recording from Taste Receptor Cells of Channel Catfish and Larval Tiger Salamander, J. H. Teeter Patch-Clamping of Taste Cells in Hamster and Rat, T. A. Gilbertson Patch-Clamping of Taste Cells in Mouse, J. F. MacDonald, I. Mody, M. W. Salter, and A. I. Spielman Loose-Patch Recording from Taste Buds in Situ, B. Lindemann Patch-Clamping Lobster Olfactory Receptor Cells, B. W. Ache, D. A. Fadool, and A. Zhainazarov Patch-Clamping of Whole Olfactory Cilia, S. J. Kleene Patch-Clamping Techniques for Vertebrate Olfactory Receptor Cells, G. Lowe, T. Nakamura, and G. H. Gold Single Unit and Electroantennogram Recordings in Insect Olfactory Organs, K.-E. Kaissling Patch-Clamping of Olfactory Cells in Insects, F. Zufall Imaging of Intracellular Calcium in Chemosensory Receptor Cells, D. Restrepo, M. Zviman, and N. E. Rawson Videorate Imaging of Potentiometric Dyes in Olfactory Research, J. S. Kauer Methods to Study Flow Dynamics in Olfaction, P. W. Scherer, K. Keyhani, I. Hahn, and M. Mozell Applications of Molecular Biology to Chemosensory Research Cloning of Gustatory cDNAs and Analysis of Their Pattern of Expression, P. J. McKinnon, S. K. McLaughlin, and R. F. Margolskee Cloning of Odorant Receptors, E. R. Liman and L. B. Buck List of Critical References for Techniques Not Covered

Abstract: Ensheathing cells are the glial cells that ensheath olfactory axons within both the PNS and CNS portions of the primary olfactory pathway. These glial cells express a mixture of astrocyte-specific and Schwann cell-specific phenotypic features, support axonal growth by olfactory as well as by non-olfactory neurons, and survive transplantation into injured areas of the CNS.This review article focuses on those phenotypic features that are expressed by ensheathing cells that make them ideal candidates for transplantation into wound cavities in the damaged spinal cord of humans. Although much work remains to be done before such a therapeutic approach can be tried, the likelihood that ensheathing cells could simultaneously perform the roles of both astrocytes and Schwann cells following transplantation is the justification for developing such a therapeutic approach using animal models of spinal cord injury.

Abstract: A central problem in sensory system biology is the identification of the signal transduction pathways used in different sensory modalities. Genetic analysis of transduction mutants provides a means of studying in vivo the contributions of different pathways. This report shows that odorant response in one olfactory organ of Drosophila melanogaster depends on the norpA phospholipase C (EC 3.1.4.3) gene, providing evidence for use of the inositol 1,4,5-trisphosphate (IP3) signal transduction pathway. Since the norpA gene is also essential to phototransduction, this work demonstrates overlap in the genetic and molecular underpinnings of vision and olfaction. Genetic and molecular data also indicate that some olfactory information flows through a pathway which does not depend on norpA.

Abstract: Olfactory auras accompany some cases of epilepsy. Several aspects of olfactory function, including sensitivity, also may be altered. We reviewed the literature on these topics, as well as studies evaluating the influences of temporal lobe resection and other seizure management procedures on olfactory function. We concluded that: (a) despite several studies, the prevalence of olfactory auras in epilepsy is unknown, with estimates ranging from 30%; (b) epilepsy appears to cause a generalized decrease in olfactory functioning, although increased sensitivity may occur in some epileptic patients at some time in the preictal period; (c) other sensory modalities are also affected by the epileptic process which, in some cases, involve limbic-related temporal lobe structures; (d) many of the olfactory deficits previously attributed to temporal lobe resection actually exist preoperatively; (e) a taste/flavor confusion exists in the reporting of taste auras; (f) unpleasant auras are associated with hyperresponsiveness of neurons, which may explain why most epilepsy-related olfactory auras are described as "bad"; and (g) interesting parallels exist between the effects of the neuroendocrine system on seizure activity and olfactory function.

Abstract: Evidence that odors can be learned prenatally further blurs the distinction between inborn and acquired responses and provides an unusual opportunity to investigate processes underlying the acquisition of information during the earliest stages of development (reviewed in [1]). This is particularly well illustrated by the development of food preference in the European rabbit (Oryctolagus cuniculus). Doe rabbits visit and nurse their young for only 3 to 4 min each day and usually wean them abruptly at about day 26 in preparation for the next litter. Under such circumstances, the young have little opportunity to learn what to eat from their mother by direct behavioral observation, but may do so indirectly by the preand postnatal acquisition of chemical information associated with her diet [2]. If pregnant does are fed aromatic juniper berries, which form part of the rabbit's natural diet, then at weaning, their pups demonstrate a preference for juniper, even if raised by a foster mother fed standard laboratory food and thus without postnatal juniper experience [2]. Although the development and expression of preferences certainly depends on central mechanisms, we speculated that such exposure learning, occurring in the apparent absence of conventional reinforces, might also be associated with the enhanced development of subpopulations of sensory cells or their receptors, and result in greater sensitivity to odors experienced during early life. Such enhancement seemed possible for several reasons: the clear evidence for prenatal odor perception accompanied by a substantial increase in the number of sensory cells, which occurs in the rabbit even postnatally [31, our experience that this increase is dependent on environmental stimulation during the first few days after birth [4], and the narrowing of the response profile of sensory cells reported to occur in the rat immediately before birth [5]. As a first test of this hypothesis, it was the purpose of the present study to establish whether prenatal experience of the mother's diet could be demonstrated behaviorally in newborn rabbits immediately after birth, and whether stimulus-specific, prenatal enhancement of sensitivity could be demonstrated postnatally by recording the electro-olfactogram (EOG), that is, the change in voltage across the olfactory epithelium in response to olfactory stimulation [6]. For this, pups were separated from their mother at birth and behavioral tests were conducted on the first postnatal day before the first suckling experience. All animals for which electrophysiological data were obtained continued to be tested each day until recording of the EOG either on days 1 3 or days 9-14. Domestic, chinchilla-breed rabbits (Chbb, Thomae, Biberach) were used. From mid gestation, 10°70 of the experimental does' daily ration of lab food (Altromin) was replaced by dried, commercially available juniper berries, whereas control does received the standard diet only. To establish whether learning had occurred, and thus that experimental litters had indeed been exposed to juniper, pups were tested for 3 min each day in a 22x32 cm arena containing three freshly chopped juniper berries beneath the wire-mesh floor at one end. The time pups spent on each side of the arena was recorded, and the number of trials in which one or the other side was preferred by control and experimental animals was compared using the chisquare test. Whereas control pups tended to avoid the juniper odor, pups from experimental mothers showed a clear preference for it, and throughout the 8-day test period spent more time in a greater number of trials on the scented side than controls (Fig. 1, p < 0.001). This was the case even on day 1, thus demonstrating the effectiveness of the prenatal treatment (p < 0.001). To investigate the influence of this odor experience on the functional properties of the olfactory epithelium, randomly selected pups were sacrificed and the nasal septum removed. To record the EOG, the epithelium was placed on a silver-plated spoon and kept moist with saline solution. The surface electrode, an agarand saline-filled glass pipette (30-40 ~tm 2~) containing a silver chloride wire, was positioned at the approximate center of the epithelium between the accessory olfactory nerves which served as landmarks. EOG potentials were monitored on an oscilloscope and a polygraph. The odorants juniper oil (V6gele, Stuttgart), and as a reference stimulus, isoamyl acetate (Merck) were delivered as a fivefold dilution series (1 ml vapor/600ms every 2rain) into a continuous, moisturized stream of oxygen (200ml/min) using a syringe olfactometer. At each dilution step, each odorant was delivered alternately, and three such dilution series, separated by a blank, were recorded for each animal. Stimulation with either odorant resulted in consistent, concentration-dependent amplitudes in both the juniper-exposed and control epithelia (Fig. 2). However, comparing the amplitudes for juniper with those for isoamyl acetate showed the juniper amplitudes to be relatively greater for epithelia from the exposed than from the control animals. When for each animal and dilution step, the relative dif-

Abstract: Neuropathology in Huntington's disease (HD) known to project to areas that process olfactory information raises the questions of which olfactory function, if any, is most affected in HD, and how to explain such dysfunction in terms of olfactory sensitivity and cognition. These questions were studied by comparing HD patients and controls (matched for age, gender, and education) on absolute detection, intensity discrimination, quality discrimination, short-term recognition memory, and lexical- and picture-based identification for odor. Taste or vision were used as comparison modalities. The results suggest that whereas odor-recognition memory is not affected in patients with HD, these patients have impaired olfactory functioning with respect to absolute detection, intensity discrimination, quality discrimination, and identification. The three latter impairments were significantly explained by poor detection sensitivity. Odor identification was the function most affected.

Abstract: Freshwater crayfish have well-developed olfactory systems with an array of receptors that project exclusively to areas in the brain that are functionally specialized for the processing of odors. The accessory lobes are large bilateral areas of neuropil that are anatomically associated with the olfactory lobes. The accessory lobes receive no primary afferents and do not contain the endings of motor efferents; thus, their role in olfaction is still obscure. Intracellular dye filling of interneurons in the deutocerebral commissure in the crayfish brain has shown that they end bilaterally in glomeruli in the accessory lobes, have cell somata in a dorsal cluster medial to the olfactory lobes, and have unilateral projections to the deutocerebral commissure neuropil. Each deutocerebral commissure interneuron has only 6 to 15 output glomeruli in each accessory lobe and does not share glomeruli with other deutocerebral commissure interneurons. The deutocerebral commissure interneurons converge with the dorsal giant serotonin neurons in the accessory lobe glomeruli. Deutocerebral commissure interneurons can be separated into classes according to their projections to the protocerebrum, central body, and deutocerebrum. Physiological responses of the deutocerebral commissure interneurons following photic stimulation of the eyes and electrical stimulation of the second antennae lead to the conclusion that the deutocerebral commissure represents an input to the accessory lobes from the protocerebral neuropils and that visual and tactile inputs are included in the processing performed in the accessory lobes. © 1995 Wiley-Liss, Inc.

Abstract: Deposition of beta-amyloid (A beta) in senile plaques is a major pathological characteristic of Alzheimer's disease A beta is generated by proteolytic processing of amyloid precursor proteins (APP) APP is a member of a family of related polypeptides that includes amyloid precursor-like proteins APLP1 and APLP2 To examine the distribution of APLP2 in the nervous system, we generated antibodies specific for APLP2 and used these reagents in immunocytochemical and biochemical studies of the rodent nervous system In this report, we document that in cortex and hippocampus, APLP2 is enriched in postsynaptic compartments In the olfactory system, however, APLP2 is abundant in olfactory sensory axons, and axon terminals in glomeruli Confocal microscopy revealed that APLP2 is present in both pre- and postsynaptic compartments in the olfactory bulb Notably, mRNA encoding chondroitin sulfate glycosaminoglycan (CS GAG)-modified forms of APLP2 are enriched in the olfactory epithelium, relative to alternatively-spliced mRNA, encoding CS GAG-free forms of APLP2 In addition, we demonstrate that CS-modified APLP2 forms accumulate in the olfactory bulb CS proteoglycans are known to play an important role in regulating cell migration and neuronal outgrowth Since sensory neurons in the olfactory epithelium are in a state of continual turnover, axons of newly generated cells must establish synaptic connections with neurons in the olfactory bulb in adult life The presence of APLP2 in olfactory sensory axons and glomeruli is consistent with the view that this protein may play an important role in axonal pathfinding and/or synaptogenesis

Abstract: The high concentration and the localization of nitric oxide synthase in the olfactory system of both vertebrates and invertebrates suggest that the diffusible messenger nitric oxide plays a central role in the processing of chemosensory information. This paper describes the nitric oxide releasing system in the antenna and the antennal lobes of Apis mellifera using the NADPH diaphorase technique, and analyses the contribution of the nitric oxide system in the neuronal processing of chemosensory signals using a behavioural assay in vivo. In the antenna the strongest NADPH diaphorase staining is found in non-neuronal auxiliary and/or epithelial cells, while the sensory cells and the antennal nerve are stained at a low level. At the major site of chemosensory signal integration, the antennal lobes, the highest nitric oxide synthase activity is located in the glomeruli, which are ideally suited to act as diffusion compartments. We demonstrate that inhibition of nitric oxide synthase in the antennal lobes specifically interferes with neuronal processing of repetitive chemosensory stimuli but does not affect the response to single stimuli, and is independent of parameters such as satiation level, stimulus strength, interstimulus interval and duration of sensory stimuli. Since inhibition of the soluble guanylate cyclase, a major target of nitric oxide, also particularly affects the adaptive component, the physiological effects of nitric oxide appear to be mediated by the action of cGMP. These findings suggest that the nitric oxide/cGMP system in the antennal lobes is a component of the molecular machinery involved in adaptive and/or integrative mechanisms during chemosensory information processing in vivo.

Abstract: Immunohistochemistry by using monoclonal antibodies named A5 and B2, which specifically recognize cell surface proteins the neuropilin and the plexin, respectively, revealed that olfactory axons in Xenopus tadpoles were classified into several subgroups by virtue of the expression levels of these two cell surface molecules. The vomeronasal axons expressed the plexin but not the neuropilin. The plexin-positive and neuropilin-negative vomeronasal axons form a discrete fiber bundle, even after they joined with the principal olfactory axons. However, the principal olfactory axons were divided into at least two subclasses; the neuropilin-predominant axons which expressed high levels of the neuropilin and low levels of the plexin, and the plexin-predominant axons which expressed high levels of the plexin and low levels of the neuropilin. Within the olfactory nerve the pathways for these two principal olfactory axon subclasses were initially intermingled with each other, but were gradually segregated throughout their courses from the nose to the cerebrum. Eventually, the neuropilin-predominant and the plexin-predominant principal olfactory axon subclasses projected to specified glomeruli in topographically related regions within the main olfactory bulb. Neuroanatomical tracings of the olfactory projection also confirmed the gradual segregation of the pathways for the principal olfactory axons. These results allow us to speculate that both the neuropilin and the plexin are involved in axon interactions, and play roles in the organization of the precise patterns of the olfactory pathway and projection.

Abstract: The expression of the olfactory cyclic nucleotide-gated channel (CNG1) was studied in the rat brain. Using RT-PCR, levels of CNG1 mRNA were determined relative to the expression of a constantly expressed gene, alpha-tubulin. RT-PCR showed that CNG1 mRNA was detectable in the pituitary gland, the olfactory bulb, and the cerebellum of adult and 5-day-old rats. A 3.4 kb mRNA was detected in the olfactory bulb by Northern blotting. In situ hybridization analysis showed that CNG1 mRNA expression is present in the olfactory bulb and in the Purkinje cells of the cerebellum. RT-PCR studies on Purkinje cell-enriched cultures obtained from the cerebellum of 16-day-old embryos (E16) confirmed the expression of CNG1 mRNA in these neurones. Our results show that CNG1 is not restricted to the olfactory epithelium but is also present in specific regions of the brain. These results suggest that cyclic nucleotides may act in the regions that possess CNG1 gene expression to affect the electrical activity of certain neurones directly.

Abstract: B-50/GAP-43, a neural growth-associated phosphoprotein, is thought to play a role in neuronal plasticity and nerve fiber formation since it is expressed at high levels in developing and regenerating neurons and in growth cones. Using a construct containing the coding sequence of B- 50/GAP-43 under the control of regulatory elements of the olfactory marker protein (OMP) gene, transgenic mice were generated to study the effect of directed expression of B-50/GAP-43 in a class of neurons that does not normally express B-50/GAP-43, namely, mature OMP-positive olfactory neurons. Olfactory neurons have a limited lifespan and are replaced throughout adulthood by new neurons that migrate into the upper compartment of the epithelium following their formation from stem cells in the basal portion of this neuroepithelium. Thus, the primary olfactory pathway is exquisitely suited to examine a role of B-50/GAP- 43 in neuronal migration, lifespan, and nerve fiber growth. We find that B-50/GAP-43 expression in adult olfactory neurons results in numerous primary olfactory axons with enlarged endings preferentially located at the rim of individual glomeruli. Furthermore, ectopic olfactory nerve fibers in between the juxtaglomerular neurons or in close approximation to blood vessels were frequently observed. This suggests that expression of B-50/GAP-43 in mature olfactory neurons alters their response to signals in the bulb. Other parameters examined, that is, migration and lifespan of olfactory neurons are normal in B-50/GAP-43 transgenic mice. These observations provide direct in vivo evidence for a role of B-50/GAP-43 in nerve fiber formation and in the determination of the morphology of axons.

Abstract: 1. The effect of the putative neural messenger carbon monoxide (CO) and the role of the cGMP second-messenger system for olfactory signal generation was examined in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With the use of whole cell voltage-clamp recordings in combination with a series of ionic and pharmological tests, it is demonstrated that exogenously applied CO is a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels previously described to mediate odor transduction. 3. Several lines of evidence suggest that CO mediates its effect through stimulation of a soluble guanylyl cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion is based on the findings that CO responses show an absolute requirement for guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect of CO on CNG currents in the absence of GTP is detectable, and that a blocker of sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation. This analysis implies that CO is a potent activator of olfactory sGC. 5. Perforated patch recordings using amphotericin B demonstrate that low micromolar doses of CO effectively depolarize the membrane potential of ORNs through tonic activation of CNG channels. This effect in turn regulates excitable and adaptive properties of ORNs and modulates neuronal responsiveness. 6. These data argue for an important role of the cGMP pathway in olfactory signaling and support the idea that CO may function as a diffusible messenger in the olfactory system.

Abstract: In chemosensory systems, a variety of lipophilic ligand-binding proteins have been found in saliva or nasal mucus. Lipophilic stimulants reach the receptor membrane, carried by these proteins. An acidic 14-kDa protein purified in the blowfly, Phormia regina, belongs to the insect pheromone-binding protein superfamily, but unlike other lipophilic ligand-binding proteins in insect or vertebrate chemosensory systems, it was distributed in both taste and olfactory organs. A similar protein was also isolated in Drosophila melanogaster. Considering their distributions, cDNA sequences and structural features, we concluded that these proteins belong to a unique subfamily whose members have convergently evolved for a common function required for both senses of taste and olfaction. By an electrophysiological experiment using antiserum, we also suggested that these proteins carry fragrant components of natural foods in taste systems as well as in olfactory systems.