Biomedical subjects

A Holley

Publications and source records attributed to A Holley.

At least 19 recordsLinked to original sources

PubMed2001

Functional neuroanatomy of different olfactory judgments.

Humans routinely make judgments about olfactory stimuli. However, few studies have examined the functional neuroanatomy underlying the cognitive operations involved in such judgments. In order to delineate this functional anatomy, we asked 12 normal subjects to perform different judgments about olfactory stimuli while regional cerebral blood flow (rCBF) was measured with PET. In separate conditions, subjects made judgments about the presence (odor detection), intensity, hedonicity, familiarity, or edibility of different odorants. An auditory task served as a control condition. All five olfactory tasks induced rCBF increases in the right orbitofrontal cortex (OFC), but right OFC activity was highest during familiarity judgments and lowest during the detection task. Left OFC activity increased significantly during hedonic and familiarity judgments, but not during other odor judgments. Left OFC activity was significantly higher during hedonicity judgments than during familiarity or other olfactory judgments. These data demonstrate that aspects of odor processing in the OFC are lateralized depending on the type of olfactory task. They support a model of parallel processing in the left and right OFC in which the relative level of activation depends on whether the judgment involves odor recognition or emotion. Primary visual areas also demonstrated a differential involvement in olfactory processing depending on the type of olfactory task: significant rCBF increases were observed in hedonic and edibility judgments, whereas no significant rCBF increases were found in the other three judgments. These data indicate that judgments of hedonicity and edibility engage circuits involved in visual processing, but detection, intensity, and familiarity judgments do not.

Adult↗

PubMed1999

Stress induces neurogenesis in non-neuronal cell cultures of adult olfactory epithelium.

Among the basal cells of the olfactory epithelium is a stem cell which divides and whose progeny differentiate into new sensory neurons throughout adult life. Olfactory neurogenesis is highly regulated, for example it is stimulated by epithelial damage. Previous reports implicate several growth factors in progenitor cell proliferation and neuronal differentiation in vitro but these studies differ in growth conditions and age of donors making it difficult to determine precisely the roles of neurogenic stimuli and their sites of action. The aims of the present study were to develop purified basal cell cultures from adult olfactory epithelium and to stimulate neurogenesis in defined growth conditions in order to elucidate the cellular mechanisms by which neurogenesis is stimulated after epithelial damage. We show here that differentiated olfactory sensory neurons arise after biochemical or mechanical stress of rat and mouse olfactory epithelial cell cultures in the absence of growth factors, complex media (e.g., serum, conditioned media, pituitary and hypothalamic extracts), or other cells (e.g., explants, feeder layers of glia, or other non-epithelial cells). Prior to the stress, these cultures contained basal cells and supporting cells but not neurons. After the stress, some cells differentiated into bipolar neurons expressing a number of neuronal proteins including olfactory marker protein. Bromodeoxyuridine experiments show that the differentiated neurons arose from recently divided cells which did not divide again before differentiating. We conclude that stress disrupts cell surface contacts to induce the immediate neuronal precursors to undergo final differentiation into olfactory sensory neurons. This may be a mechanism for enhanced neurogenesis after epithelial damage.

Age Factors↗

PubMed1999

Functional anatomy of perceptual and semantic processing for odors.

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.

Adult↗

PubMed1999

Implementing the right to community integration for children with disabilities in Russia: a human rights framework for international action.

Human rights organizations have documented a widespread pattern of abuse in Russia's orphanages and institutions for children with disabilities. Community integration is critical to attack the underlying causes of discrimination and abuse of children in institutions. While there is an immediate need to protect children in institutions, investment in improving orphanages may inadvertently strengthen an outmoded system of segregated services, delaying long-term reform. This article describes a response to abuses in institutions based on the internationally recognized right to community integration for all children, including children with mental and physical disabilities. While tailored to Russia, the framework for action described here applies to many countries in which children and adults with disabilities are similarly segregated from society in closed institutions.

Child↗

PubMed1998

Generation of neurons from a nonneuronal precursor in adult olfactory epithelium in vitro.

Within the olfactory epithelium is a stem cell which can divide and differentiate to produce new sensory neurons. The identity of the neuronal stem cell is unknown but one candidate is the horizontal basal cell which lies adjacent to the basement membrane and expresses keratin. Previous attempts to generate mature sensory neurons from purified horizontal basal cells in vitro were unsuccessful. We show here for the first time that olfactory neurogenesis can be reproduced in vitro from partially-purified cultures of adult rat precursor cells cultivated in a serum-free medium. Rat olfactory epithelium was dissected from the nasal septum and separated from the underlying lamina propria, and its cells were dissociated and grown in a medium containing epidermal growth factor for 5 days. Immunochemistry showed that only supporting cells (SUS1-positive) and horizontal basal cells (keratin-positive) survived for this period. At day 6, the cells were stressed either by passaging them or by a simple mechanical stress. In each case, a morphological and immunological differentiation was observed within 24-48 hr. Newly formed bipolar cells were found to be S100-, glial fibrillary acidic protein (GFAP-), neural cell adhesion molecule (N-CAM+), and/or microtubule-associated protein 5 (MAP-5+). After passaging 14% of the surviving cells were immature neurons (MAP-5+) and 4% were mature olfactory neurons (MAP-5+) and olfactory marker protein (OMP+)). In addition the same experiment was conducted on transgenic mice in which the lacZ gene was linked to the OMP promoter. Using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining we showed that OMP+ cells disappeared before day 5 in culture but reappeared after passaging. These results suggest that olfactory sensory neurons can arise from a non-neuronal precursor, probably the keratin-positive horizontal basal cell.

Animals↗

PubMed1997

Eyewitness performance in cognitive and structured interviews.

This paper addresses two methodological and theoretical questions relating to the Cognitive Interview (CI), which previous research has found to increase witness recall in interviews. (1) What are the effects of the CI mnemonic techniques when communication techniques are held constant? (2) How do trained interviewers compare with untrained interviewers? In this study, witnesses (college students) viewed a short film clip of a shooting and were questioned by interviewers (research assistants) trained in conducting the CI or a Structured Interview (SI)--similar to the CI except for the "cognitive" components--or by untrained interviewers (UI). The CI and SI groups recalled significantly more correct information compared to the UI group. However they also reported more errors and confabulated details. Theoretical and practical implications of the results are discussed in terms of precisely identifying the CI facilitatory effects and consequent good practice in the forensic setting.

Adolescent↗

PubMed1997

Role of verbal encoding in short- and long-term odor recognition.

The role of verbal encoding in odor recognition memory was investigated using odors of low familiarity to subjects before the experiment began. The experimental procedure included two phases--odor learning (first phase) and odor memory testing (second phase)--separated by a delay of 7 days. Five experimental conditions were established: three conditions of odor learning with names (labeling conditions), one condition of odor learning without names (sensory familiarization), and one condition of no learning prior to testing (control conditions). The labeling conditions differed from each other regarding label characteristics. The names were those of odor sources (veridical names), those personally generated by subjects (generated names), or those derived from the chemical names of the odorants (chemical names). Subjects were required to learn 20 fixed associations between odors (targets or distractors) and 20 names during two daily sessions. The learning sessions included two identification tests and ended by a verbal memory test in which subjects recalled odor names. The odor memory test was split into two parts separated by a retention interval of either 20 min (short-term memory) or 24 h (long-term memory). Data showed that olfactory recognition memory was enhanced in subjects who associated veridical or generated names to odors during the learning session. Chemical names were not appropriate to facilitate odor recognition. Similarly, the level of odor identification was higher for veridical and generated names than for chemical names, though the level of verbal memory for chemical names was substantial. Recognition response latencies were systematically longer for a target odor implying a positive response than for a distractor odor implying a negative response. Together, these data suggest that odor recognition and identification are sensitive to the semantic content of labels associated with odors. Odor memory was adversively influenced by time, but this influence was less pronounced when the names were endowed with a rich semantic content.

Adolescent↗

PubMed1995

Temporal competition between odorants: effect of different time intervals on the perception of monorhinic and dichorhinic binary mixtures.

Backward masking and its possible connection with the perception of odour mixtures has been investigated. Temporal competition between odorants in a binary mixture was tested by artificially creating a delay between one odour (the target) and a second, stronger, odour (the mask) during a single natural sniff. To test the influence of central versus peripheral competition, the same mixture was presented either monorhinically or dichorhinically. The delay (100 to 400 ms) did not influence intensity perception, indicating that intensities are integrated during the sniff irrespective of the temporal arrangement. In contrast, the number of qualities perceived was influenced by the delay: delays of 200 to 400 ms gave significant increases in the frequency of detection of a mixture, whereas synchronous mixtures favoured the perception of a single odour. Masking was also significantly stronger in dichorhinic mixtures. These effects are discussed in terms of retroactive masking which seems to be enhanced by dichorhinic mixtures, suggesting that masking has an important central component.

Adult↗

PubMed1995

Odor discrimination and recognition memory as a function of familiarization.

The role of olfactory familiarization in short-term recognition of odors was investigated. Subjects were asked to make qualitative similarity judgments regarding either identical or dissimilar odors delivered in pairs. Except for control groups, subjects got familiarized with either the first (target) or the second (distractor) or both odors from a pair. Groups also differed according to the number of familiarization sessions--one, two, or three--taking place prior to the discrimination judgments. There was no significant influence of familiarization on correct recognition scores for pairs of identical odors. The most salient finding was a marked decrease of false alarms as a function of the number of familiarization sessions, which evidenced a positive effect of familiarization on discrimination for pairs of dissimilar odors. These judgments were not dependent on an intensity criterion. False alarms did not vary according to whether subjects had been familiarized with the target or the distractor or both odors from a pair. A positive correlation found between discrimination performances and the number of odors correctly remembered as being presented during familiarization suggested that familiarization resulted in long-term storing of memory traces for familiarized odors. Since familiarization was effective despite conditions unfavorable to the use of semantic encoding, the results argue in favor of a predominantly perceptual encoding of odors in the investigated task.

Adult↗

PubMed1994

Very short term recognition memory for odors.

An investigation of very short term olfactory recognition memory was made with odors of low familiarity to subjects. The experimental procedure was that currently used to make qualitative similarity judgments on odors delivered in paired succession. Subjects made similarity judgments in a yes/no recognition paradigm on odors that were either identical or different. The dependence of recognition performance upon the degree of qualitative similarity was assessed by using two sets of dissimilar odor pairs: slightly dissimilar pairs (S1) and very dissimilar pairs (S2). Performance in terms of correct judgments (hits, correct rejections) was rather good for identical pairs in both sets and was nearly perfect for very dissimilar pairs with a delay of 2-300 sec, suggesting no effect of time or similarity on performance. However, for slightly dissimilar pairs, false alarms increased in number, thereby indicating a dependence of the recognition score on the qualitative distance between odors. In addition, false alarms tended to increase with the lengthening of the retention interval. It was suggested that the subjects based their responses on their capability to detect differences between odors rather than recognizing their similarities. Correct identifications were thus preserved at the cost of increasing false alarms when the discrimination task was made more difficult by closer similarity between odors (S1) or by the fading of memory traces with time. Studying the congruence between the similarity judgments and the kind of evocations associated with paired odors gives some support to the view that recognition performances had some cognitive/semantic basis.

Adult↗

PubMed1993

Involvement of the olfactory bulb in consolidation processes associated with long-term memory in rats.

In a daily training paradigm, rats were trained to discriminate between spatially distinct electrical stimulations delivered to one olfactory bulb. Xylocaine injections were used to disrupt the olfactory bulb functioning in the region close to the electrode tips for 1 hr after training session. The treatment started either just after the session or 2 hr later. When compared with the performance of saline-injected rats, the performance of Xylocaine-injected rats was unimpaired except when the treatment started just after the daily session. In that case, acquisition of the task was slightly altered, and retention over a 5-day period was dramatically impaired. We therefore concluded that, within about 1 hr following training, the olfactory bulb is engaged in consolidation processes critical for long-term retention of learned olfactory cues.

Animals↗

PubMed1992

Morphological variations among output neurons of the olfactory bulb in the frog (Rana ridibunda).

Morphological properties of putative output cells have been studied in detail in the olfactory bulb of frogs (Rana ridibunda). Intracellular injection of Lucifer Yellow was used to reconstruct individual neurons. Ten different anatomical features related to cell shape and position were studied quantitatively. The results show that output cells, generally considered to be a homogeneous group in the olfactory bulb of amphibians, are, in fact, quite different in their morphology. Using multidimensional analysis to examine differences among the output neurons, we found that they might be divided into at least two groups. In one group, the cell somata were located near the glomerular layer and the dendrites lay at large angles with respect to each other. In the other group, the cell somata were farther from the glomerular layer and their dendrites lay at smaller angles. From their morphology, these two cell groups appear to be homologous, respectively, to the superficial/middle tufted cells and deep tufted/mitral cells of mammals.

Animals↗

PubMed1992

Some properties of receptive fields of olfactory mitral/tufted cells in the frog.

1. Different regions of the frog's olfactory epithelium were stimulated with nine glass micropipettes either individually or simultaneously in different combinations. The stimulus was a positive electrical pulse (4 s) consisting of a progressive increase, a plateau, and a progressive decrease in current intensity. Extra- and intracellular recordings were made from olfactory bulb mitral/tufted cells. Some of these cells were identified by intracellular injection of Lucifer yellow. 2. The action potential response patterns of mitral/tufted cells during the different phases of the stimulation were coded according to whether the activity was increased or decreased compared with its spontaneous level just before stimulation. Neural responses were classified into 11 types: individual neurons responded with different response types to stimuli delivered at different epithelial sites. On the basis of these response types, it was found that neurons could be classified into two groups. All response types in one group included an initial phase of increased discharge (excitation), whereas all types in the other group included an initial phase of decreased activity (suppression). Neurons that displayed response types belonging to one group never displayed those of the other group. It was thus concluded that a given neuron responded either always with an increased activity or always with a decreased activity, whatever the location of the stimulus. 3. The receptive field of a mitral/tufted cell appeared to be homogenous and not divided into areas of different properties, at least under the present experimental conditions. The extent of a receptive field was estimated by determining the number of effective epithelial sites (where an electrical stimulus evoked a response from a bulbar neuron).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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↗