Biomedical subjects

A Holley

Publications and source records attributed to A Holley.

At least 37 records · Page 2Linked to original sources

PubMed1991

Spread of the CVS strain of rabies virus and of the avirulent mutant AvO1 along the olfactory pathways of the mouse after intranasal inoculation.

After intranasal instillation in the mouse, rabies virus (CVS strain) selectively infected olfactory receptor cells. In the main olfactory bulb (MOB), infection was observed in periglomerular, tufted, and mitral cells and in interneurons located in the internal plexiform layer. Beyond the MOB, CVS spread into the brain along the olfactory pathways. This infection is specific to chains of functionally related neurons but at the death of the animal some nuclei remain uninfected. CVS also penetrated the trigeminal system. The avirulent mutant AvO1, carrying a mutation in position 333 of the glycoprotein, infected the olfactory epithelium and the trigeminal nerve as efficiently as CVS. During the second cycle of infection, the mutant was able to infect efficiently periglomerular cells in the MOB and neurons of the horizontal limb of the diagonal band, which indicates that maturation of infective particles is not affected in primarily infected neuronal cells. On the other hand, other neuronal cells permissive for CVS, such as mitral cells or the anterior olfactory nucleus, are completely free of infection with the mutant, indicating that restriction is related to the ability of AvO1 to penetrate several categories of neurons. From these observations, we concluded that CVS should be able to bind several different receptors to penetrate neurons, while the mutant would be unable to recognize some of them.

Administration, Intranasal↗

PubMed1990

Strain and sex differences in the response of mice to drugs that induce protoporphyria: role of porphyrin biosynthesis and removal.

A hepatic green pigment, inhibitory toward ferrochelatase, has been isolated from the liver of mice treated with griseofulvin, isogriseofulvin, or 3,5-diethoxycarbonyl-1,4-dihydrocollidine and has been shown to exhibit identical chromatographic characteristics to authentic N-methyl protoporphyrin. All four possible structural isomers have been demonstrated, and each drug produced primarily the same isomer. N-Methyl protoporphyrin has also been found in very small amounts in the liver of untreated mice, but the isomeric composition appeared to differ from that of the drug-induced N-methyl protoporphyrin. Intraperitoneal administration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine to female C3H/He/Ola and NIH/Ola inbred mice produced a marked dose-related loss of hepatic ferrochelatase activity, which was identical in magnitude in the two strains. Induction of hepatic 5-aminolevulinate synthase (ALA-S), and accumulation of liver protoporphyrin, however, were greater in C3H/He/Ola mice. The strain difference in ALA-S response was most marked when inhibition of ferrochelatase (the "specific" effect of the drug) was maximal, and this suggests that a genetic variation exists in the sensitivity of ALA-S to a second drug action, the so-called nonspecific action, which is shared by many lipid-soluble compounds. Male mice of three strains accumulated greater amounts of hepatic protoporphyrin than females after treatment with griseofulvin, yet no significant difference was found between the two sexes in the extent of ferrochelatase inhibition. Stimulation of ALA-S activity was slightly greater in males, but when porphyria was very marked, ALA-S activities were significantly lower in this sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

An investigation of some temporal aspects of olfactory coding with the model of multi-site electrical stimulation of the olfactory bulb in the rat.

Electrical stimulation of the olfactory bulb was used to investigate some temporal aspects of olfactory coding, with reference to respiration. Food-deprived rats implanted with permanent electrodes were trained to use bulbar multi-site stimulation patterns as discriminative stimuli for predicting the nature of an incoming reinforcement. Electrical pulse trains (100 Hz) were periodically delivered in phase with precisely defined moments of the respiratory cycle (during inspiration or expiration). Temporal aspects of olfactory coding were first considered through the measurement of the minimum duration of a stimulus necessary to identify this stimulus. The results showed that a bulbar stimulation lasting for 30 ms (3 pulses), and delivered during inspiration, was clearly identified by the rats. Stimulus identification induced a discriminative respiratory response which could manifest itself as early as the first cycle concomitant with the beginning of stimulation. It was then shown that a bulbar electrical stimulation pattern was identified with the same latency whether it occurred during expiration or during inspiration. Moreover, the perceptive events induced in those two conditions of stimulation were not different enough to be discriminated by the animals. The findings are discussed within the framework of olfactory information processing.

Animals↗

PubMed1989

Peptidergic regulation of secretory activity in amphibian olfactory mucosa: immunohistochemistry, neural stimulation, and pharmacology.

The role of substance P in the regulation of secretion from sustentacular cells, Bowman's glands and deep glands in the amphibian olfactory mucosa was investigated using immunohistochemical, electrophysiological, and pharmacological methods. Substance P-like immunoreactive varicose fibers extended through the olfactory epithelium, terminating at or near the surface. In addition, immunoreactive varicose fibers innervated Bowman's glands, deep glands, and blood vessels in the lamina propria. Innervation of Bowman's gland was sparse, with fibers terminating on basal acinar cell membranes; deep gland innervation was abundant, with fibers often extending between acinar cells almost to the lumen. Stimulation of the ophthalmic branch of the trigeminal nerve resulted in slow potentials recorded at the surface of the olfactory epithelium. When the olfactory mucosae from trigeminal-stimulated animals were examined histologically, morphological signs of secretory activity were observed, suggesting that substance P was released from the trigeminal nerve terminals. Topical application of 10(-5) to 10(-3) mol substance P resulted in morphological signs of secretion that were very similar to those seen as a result of trigeminal stimulation. Thus, substance P released from trigeminal fibers may modulate secretory activity within the olfactory mucosa.

Animals↗

PubMed1988

The activity of olfactory receptor cells is affected by acetylcholine and substance P.

The effects of acetylcholine (ACh) and substance P (SP) on the unit activity of receptor cells recorded from the superfused frog olfactory mucosa were studied. Single neurones were excited or, more rarely, depressed by the application of chemicals. Cholinergic antagonists were used to investigate the involvement of nicotinic and muscarinic receptors in the recorded responses. The ACh-evoked firing was antagonized by D-tubocurarine (D-TC), atropine (ATR) and SP. Responses to SP appeared to be D-TC resistant, but activation by the peptide was moderately antagonized by ATR. The results suggest that ACh and SP could affect the functioning of the olfactory receptor cells.

Acetylcholine↗

PubMed1987

Topographical relationships between olfactory receptor cells and glomerular foci in the rat olfactory bulb.

We have studied the distribution patterns of olfactory receptor cells that project to glomerular foci after HRP injections in the different bulbar surfaces of 15-day-old rats. HRP label overlapped only 2-4 contiguous glomeruli and had a maximal extent of 260 micron along the antero-posterior (A-P) axis. HRP injections were confined enough to allow labeled individual receptor cells to be discerned in the epithelial sheet. Results have shown that neurons ending in a few contiguous glomeruli of a given bulbar surface were distributed in most of the regions projecting to this bulbar surface. Moreover, within these epithelial areas, labeled cells were largely dispersed in both the frontal and the A-P axes of the nose. When few HRP-filled neurons were observed on a turbinate or a recess, their distribution seemed organized according to a certain alignment along the A-P nasal axis. Our findings demonstrate for the first time that the principal features of the regional organization of epithelium projections to a given bulbar surface are reproduced in any glomerular focus of this bulbar surface, and suggest that it could be the same for any single glomerulus. Such a principle of projection supports the concept of a large redundance in the anatomical relationship between periphery and bulb.

Animals↗

PubMed1987

Olfactory receptor cell function is affected by trigeminal nerve activity.

In the frog, antidromic electrical stimulation of the ophthalmic branch of the trigeminal nerve (NV-ob) evokes a slow potential in the olfactory mucosa, modifies the activity of receptor cells and modulates the responses to odour. Substance P (SP) application evokes similar electrical responses. These results imply that the functioning of the olfactory system might be controlled at the receptor cell level. It is suggested that the trigeminal system could modulate the activity of the olfactory receptor cells via a local axon reflex which may result in the release of SP.

Animals↗

PubMed1986

Perceptive properties of the multi-site electrical microstimulation of the olfactory bulb in the rat.

Electrical microstimulation of the olfactory bulb in different locations has been shown to provide water-deprived rats with discriminative cues for selecting a palatable solution without tasting it in a two-choice test. Some perceptive properties of bulbar electrical stimulation were investigated. It was shown that the perceptive effect evoked by stimulating a given site could be recognized when this site was stimulated together with several others. The animals' perception of multi-site stimulation patterns seems therefore to be analytical rather than synthetic. Discrimination of stimulation patterns did not require presentation of concurrent patterns inside a short time interval. Identification of a multi-site pattern was possible when this pattern was presented alone in a test session. Individual characteristics of bulbar microstimulation appear to be perceived absolutely rather than differentially. A good retention of the discrimination learning of specific stimulation patterns was observed. Animals could identify stimulation patterns after complete interruption of the training for 17 days. The results are discussed with reference to the properties of the natural stimulation of the olfactory system.

Animals↗

PubMed1985

Responses of olfactory bulb neurons to repeated odor stimulations in awake freely-breathing rabbits.

Thirty-one olfactory bulb neurons were recorded in the olfactory bulbs of unanaesthetized rabbits during repeated stimulations. Their single-unit activity associated with the inspiratory phases of the respiratory cycles and that associated with the expiratory phases were processed separately. When responses were classified into 3 types, i.e., excitation, inhibition and null, it was found that a large number of neurons presented variable responses to repeated stimulations with the same stimulus. However, the passage from one type to another was found to be limited: responses by excitation or inhibition to the first stimulation turned into null responses only; null responses turned into either excitation or inhibition. Inspiration- and expiration-related responses were also subjected to a principal component analysis in order to determine whether changes in responses were compatible with a reliable coding of the qualitative properties of a stimulus. The results indicated that the repeated presentations of an odorant induced fairly similar profiles of activity across the set of neurons while different odorants induced clearly discriminable profiles. It is concluded that repeated stimulations do not blur the characteristic features of the across-neuron profile of response of an odorant in the olfactory bulb despite the variability of the responses of the neurons which compose the profile.

Animals↗

PubMed1985

On the ability of rats to discriminate between microstimulations of the olfactory bulb in different locations.

An investigation was made into the ability of rats to discriminate between electrical stimulations applied to the mitral cell layer of the olfactory bulb in different locations. Water-deprived rats implanted with permanent electrodes were trained to use single- or multi-site microstimulations as discriminative stimuli for selecting a palatable solution without tasting it in a two-choice test. Spontaneous reactions of the animals to stimulation with sinusoidal currents higher than 3 microA per electrode resembled sensory arousal. All rats were found to discriminate between the effects of concurrent microstimulations applied to bulbar sites separated by 500 micron. Changing the current intensity in the range 4-20 microA had no detectable effect on the discrimination. Discrimination was still possible, with a few exceptions, when electrodes were separated by 250 micron and even when they were closely adjacent. Spatial resolution of discrimination seemed not to vary in different regions along the rostrocaudal axis of the bulb. The discrimination of patterns of simultaneous stimulation at several sites was also investigated. Different multi-site patterns were easily distinguished, even when their respective components were closely adjacent or when some components occupied the same area. The findings are discussed with reference to the concept of spatial coding of odours in the olfactory bulb.

Animals↗

PubMed1984

Receptor cell responses to odorants: similarities and differences among odorants.

An extensive exploration of the discriminating properties of olfactory receptors cells has been conducted in our laboratory through the statistical processing of single cell responses recorded in the frog's olfactory epithelium. Similarities between odorant stimulating properties could be demonstrated by comparing the complex response profiles of receptor cells, resulting in the concept of odorant groups which depicts consistent relationships found between some odorous compounds. The recording technique limits the number of odorants which can be tested and compared within the same series of experiments. Thus, based upon previous studies we have chosen a specific set of 20 odorants whose characteristics are known but, up to this time, have not been compared in the same experimental system. These odorants were: acetophenone, anisole, n-butanol, DL-camphor, cyclodecanone, 1,8-cineole, p-cymene, D-citronellol, n-heptanol, isoamyl acetate, isovaleric acid, D-limonene, methyl amylketone, L-menthol, phenol, thiophenol, pyridine, thymol, cyclohexanol, cyclohexanone. The pattern of similarities between these odorants, as delineated with the aid of correlation coefficient computation, factor analysis and non-hierarchical taxonomy, confirms the reality of several odorant groups previously suggested and describes their cross-relationships. The receptor mechanisms underlying these odorant groups are discussed. Because reliable prominent features of the olfactory stimulus space can be established on an objective basis, the findings are proposed as a reference for future studies on other aspects of olfactory discrimination.

Animals↗

PubMed1984

[Electrical responses of frog olfactory mucosa to the administration of acetylcholine and substance P].

The effects of acetylcholine and substance P were studied on the Frog's olfactory mucosa. Stimulation with these chemicals elicited low-threshold slow electrical potentials. Moreover, prior application of substance P strongly depressed the electrical response of the mucosa to acetylcholine. These results are discussed in relation to the possibility that acetylcholine and substance P could act on the functioning of the olfactory neuroreceptors.

Acetylcholine↗

PubMed1983

Investigations of the discriminative properties of the frog's olfactory mucosa using a photoactivable odorant.

The photoactivable compound phenylazide interacts reversibly with the frog's olfactory epithelium when delivered as an olfactory stimulus. Its application together with UV irradiation resulted in a differential reduction of the responses (electro-olfactogram) to several odorants. It was found that this chemical modification of the sensory membrane affected the responses in relative ratios which could be predicted from a classification of the odorants based upon independent studies of receptor cell odor sensitivity. The responses to chemicals representative of the 'aromatic group' were clearly more reduced than those to compounds of the 'camphoraceous group'. It is suggested that the olfactory discrimination mechanisms can be approached by the use of this method.

Animals↗

PubMed1981

[Multipolar electrical stimulation of the olfactory bulb as a model for studying spatial basis of olfactory coding].

Low-intensity electrical stimulation of the olfactory bulb through a set of spatially distributed electrodes was used as a model in order to study the spatial basis of the olfactory coding, in rats. The results indicate that this multipolar stimulation can serve as a conditional stimulus in a learned aversion paradigm; in addition, water-deprived animals displayed high ability to discriminate and memorize various combinations of electrode positions paired with differently palatable solutions.

Animals↗

PubMed1980

Spatial distribution of [14C]2-deoxyglucose uptake in the olfactory bulbs of rats stimulated with two different odours.

The uptake of [14C]2-deoxy-D-glucose (2-DG) has been studied by autoradiography in the olfactory bulbs of control and odour-stimulated rats. The sites of highest 2-DG-uptake coincide very accurately with individual glomeruli. The other bulbar histological layers appear to be far less metabolically affected by the olfactory stimulation. The mapping of the glomerular activation has been compared in two groups of animals stimulated with two different odours. The patterns of selective glomerular 2-DG-uptake are rather similar within each group. They differ from one group to the other by the number and localization of the highly labelled glomeruli. It can be inferred from our observations that a few glomeruli are metabolically highly activated by a strong and pure odour stimulation. A correlation between the quality of the odour and the pattern of glomerular activation may be supposed but has to be confirmed with other compounds.

Acetoacetates↗

PubMed1980

Single unit responses of olfactory bulb neurones to odour presentation in awake rabbits.

The changes in single unit activity induced by short odour presentations were studied in the olfactory bulbs of awake rabbits. 1. It was found that an accurate evaluation of the cell responses required the separate processing of the inspiration- and expiration-related activity. 2. Three main types of response were observed during odour presentation. One was characterized by an increase in firing over several successive inspirations, with a decrease in the corresponding expiratory phases. The other two were characterized by an inspiration-related increase or decrease in activity without any modifications during expiration. 3. The end of odour presentation led to inconsistent "off-effects" in the cells affected by the stimulation. The most conspicuous were: a complete cessation of the firing for several respiratory cycles following an excitation, an excitatory rebound following inhibition, a reversal of the respiratory phase-related discharge, i.e., activity decrease during inspiration and the increase during expiration. 4. The findings are discussed with reference to previous studies on anaesthetized animals, together with their relevance to sensory coding in the olfactory bulb.

Action Potentials↗

PubMed1979

Olfactory receptor cell activity under electrical polarization of the nasal mucosa in the frog. I. Spontaneous activity.

The electrical activity of single olfactory receptor cells was studied under electrical polarization of the olfactory epithelium in the frog. 1. The spontaneous discharge frequency varied as a linear function of the polarizing current in the range 1--20 X 10(--6)A. 2. Surface positive polarizations caused the spike activity to increase; surface-negative polarizations suppressed the activity. 3. Partial accommodation to the current was observed. 4. After-effects of short duration occurred: Rebound suppression after positive polarization, rebound excitation after negative polarization. 5. A high percentage of receptor units found in the frog's mucosa displayed no spontaneous activity.

Animals↗

PubMed1979

Olfactory receptor cell activity under electrical polarization of the nasal mucosa in the frog. II. Responses to odour stimulation.

The interactions between electrical polarizations of the olfactory epithelium and odour stimulations were investigated at the level of the extracellular spike activity of the receptor cells in the frog. 1. In most cases, surface positive polarizations enhanced the excitatory olfactory responses, negative polarizations suppressed these responses; both interactive effects were graded. 2. The response of receptor cells to electrical polarization was markedly reduced or suppressed for several seconds following olfactory stimulation. This effect and the time course of the recovery period depended on the nature and the concentration of the olfactory stimulus. 3. The decrease in electrical excitability seemed to be independent of whether the recorded neuron had responded or not to the prior olfactory stimulation. 4. It is suggested that the olfactory stimulation caused the total constant current to change its distribution in the different cell pathways. Changes in conductance induced by olfactory stimuli could implicate the supporting cells. 5. The experimental findings are discussed with reference to a model of receptor cell function that assumes a deep, axo-somatic localization of the action potential trigger-zone.

Animals↗