Biomedical subjects

D Saucier

Publications and source records attributed to D Saucier.

At least 19 recordsLinked to original sources

PubMed1997

Testing hypotheses of spatial learning: the role of NMDA receptors and NMDA-mediated long-term potentiation.

The role of NMDA receptors and NMDA-mediated hippocampal long-term potentiation (LTP) in spatial learning was studied in rats using the competitive, systemically administered NMDA receptor antagonists CGS19755 ((+/-)-cis-4-phosphonomethyl-2-piperidine carboxylic acid) and NPC17742 (2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid). CGS19755 caused sensorimotor disturbances and disrupted acquisition of the water maze in naive rats. The sensorimotor disturbances were greatly reduced and maze learning was normal in spite of the blockade of dentate gyrus LTP by CGS19755 in rats that had first been familiarized with the general task requirements by non-spatial pretraining. In a second experiment, antagonism of NMDA receptors caused small, but reliable, impairments in Y-maze and visible platform visual discrimination tasks. The results indicate that NMDA receptors are not crucial for water maze acquisition using a spatial learning strategy, and that NMDA antagonists cause visual and other sensorimotor disturbances in naive rats that could help account for their poor performance in this task.

Amino Acids↗

PubMed1996

Ultrastructural and cytochemical identification of apoptotic cell death accompanying development of the fetal rat olfactory nerve layer.

It has been previously shown that the embryonic olfactory nerve contains, in addition to glial ensheathing cells, a large population of differentiated neurons that migrate from the developing olfactory epithelium, in close association with the olfactory axon fascicles. The purpose of our study was to verify the hypothesis according to which a process of physiological cell death might be involved in the progressive disappearance of these migrating neurons that has been reported during late embryonic stages in several immunocytochemical studies. To do so, we have investigated the development of the olfactory nerve layer in rat embryos by using light and electron microscopy, with special reference to the presence of cell death processes within this structure. We have also applied the histochemical TUNEL method allowing in situ visualization of cells degenerating by apoptosis. In order to determine if neurons were present among dying cells, a procedure of double-labeling was performed by combining the DNA-specific bisbenzimide with two neuronal markers, the protein B-50/GAP-43 and the lectin Ulex europaeus I. Results brought out the precise temporal and spatial patterns of programmed cell death accompanying the morphogenesis of the olfactory nerve layer. A cell death process was observed within the olfactory nerve layer from its onset at embryonic day 13 (E13). While only few pycnotic cells were observed in E13 and E14 embryos, their number increased from E15 to reach a maximum at E16 and then diminished. Few dying cells were also observed along the olfactory axon fascicles when they penetrated the olfactory nerve layer. Degenerating cells appeared strongly TUNEL-labeled and exhibited morphological features of cell death by apoptosis. Double-labeling experiments revealed that some of the apoptotic cells were neurons. These observations indicate that apoptosis may account for the progressive decrease in the number of migrating neurons present within the embryonic olfactory nerve layer. Otherwise, a zone of massive cell death by apoptosis was observed at E14 within the nasal mesenchyme located ventrally and caudally to the olfactory nerve layer. Double-labeling experiments showed that apoptotic cells present within this zone were not neurons. Our findings strongly suggest that apoptotic cell death of migrating neurons may allow the elimination of non-functional cells whereas that of mesenchymal cells may facilitate outgrowth of the newly formed olfactory axon fascicles by pathway formation.

Animals↗

PubMed1996

Competitive NMDA receptor antagonists do not block cholinergic kindling with carbachol.

The role of NMDA receptor activity in kindling was examined in rats pretreated with the competitive NMDA receptor antagonists aminophosphonovaleric acid (APV) or NPC17742 (2R,4R,2S-(2-amino-4,5(cyclohexyl)-7-phosphonoheptanoic acid). After pretreatment, the rats received an infusion of carbachol, a muscarinic agonist, into the amygdala or hippocampus. Kindling sessions with carbachol occurred once every 48 h until a stage 5 convulsion was displayed. Electrical kindling of the amygdala after pretreatment with NPC17742 was also examined. Both APV and NPC17742 retarded the rate of carbachol kindling in its early stages, but all rats displayed kindled stage 5 convulsions under APV or NPC17742 in fewer than 10 sessions. Convulsion development was accompanied by growth in the duration and strength of the accompanying epileptiform activity. All rats exhibited a stage 5 convulsion on the first or second session after cross-over to vehicle pretreatment, confirming the development of kindled convulsions under pretreatment with NMDA antagonists. NPC17742 retarded electrical kindling, but after cross-over to vehicle there was savings in the rate of kindling to stage 5 convulsions. These findings indicate that carbachol kindling of the amygdala or hippocampus readily occurs under NMDA antagonism. They are consistent with the view that NMDA receptor activity may contribute to, but is not required for, the kindling of seizures.

2-Amino-5-phosphonovalerate↗

PubMed1996

Detailed behavioral analysis of water maze acquisition under APV or CNQX: contribution of sensorimotor disturbances to drug-induced acquisition deficits.

N-methyl-D-aspartate (NMDA) receptor antagonists disrupt acquisition of the water maze and cause sensorimotor disturbances. In a detailed behavioral analysis in male rats, it was found that the NMDA antagonist DL-2-aminophosphonovaleric acid (APV) caused sensorimotor disturbances in behaviors required for maze performance and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under APV. The results are consistent with the known role of NMDA receptors in sensorimotor mechanisms and suggest that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA may contribute to but does not appear to be essential for spatial learning in the water maze.

2-Amino-5-phosphonovalerate↗

PubMed1996

Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits.

A detailed behavioral analysis of water-maze acquisition showed that the N-methyl-D-aspartate (NMDA) antagonist NPC17742 and the muscarinic antagonist scopolamine caused sensorimotor disturbances in behaviors required for maze performances and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze in male rats. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under NPC17742 or scopolamine. The results indicated that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA or muscarinic activity may contribute to but do not appear to be essential for spatial learning in the water maze.

Amino Acids↗

PubMed1995

Spatial learning without NMDA receptor-dependent long-term potentiation.

Hippocampal lesions impair spatial learning in the watermaze. Drugs that antagonize N-methyl-D-aspartate (NMDA)-receptor activity, which is required for long-term potentiation (LTP) at various hippocampal synapses, block LTP and impair watermaze learning. This has led to the hypothesis that NMDA receptors, through their involvement in LTP, may be necessary for spatial and other forms of learning. We examined this hypothesis using NPC17742 (2R,4R,5S-2-amino-4,5-(1,2-cyclo hexyl)-7-phosphonoheptano acid), a potent and specific antagonist of NMDA receptors. Here we report that NPC17742 completely blocked dentate gyrus LTP but did not prevent normal spatial learning in rats that had been made familiar with the general task requirements by non-spatial pretraining. Although these results do not rule out a contribution of NMDA-mediated dentate LTP to spatial learning, they indicate that this form of LTP is not required for normal spatial learning in the watermaze.

Amino Acids↗

PubMed1995

Analysis of the possible altering function of the septal organ in rats: a lesional and behavioral study.

The septal olfactory organ is a small patch of sensory epithelium located on the septal wall at the entry of the nasopharynx. There is a general consensus that by sampling olfactory stimuli during periods of rest, this organ may have an alerting function. To verify this hypothesis, we have lesioned by electrocoagulation the septal organ of male rats and recorded by polygraphy their awakening reaction in response to biologically meaningful (trimethyl-thiazoline, dimethyl sulfite, food) and meaningless (geraniol, eucalyptol) odorants. The awakening reactions of both lesioned and intact rats in response to these odorants were studied according to 3 parameters, frequency, latency and duration of awakening, and were analyzed using three-way analyses of variance. Data show that no significant difference in the awakening reactions was observed between control and lesioned animals. In all cases, the biologically meaningful odors presented the highest awakening influence. In addition, two of these odors (trimethyl-thiazoline and dimethyl sulfite) elicited a later habituation in comparison to biologically meaningless odors. From our results, it could be inferred that the hypothesis regarding an alerting function that would be specific to the septal organ, appears no longer current.

Animals↗

PubMed1995

Fyn tyrosine kinase is required for normal amygdala kindling.

To identify specific genes involved with epileptogenesis kindling was examined in mice carrying mutations engineered by gene targeting. Amygdala kindling was tested in mice with a null-mutation in the Fyn tyrosine kinase gene, a mutation that raises the threshold for the induction of long-term potentiation in the hippocampus. The fyn mutants had a normal threshold, duration and stability of epileptiform after-discharge, which is crucial for kindling. Despite the normal after-discharge, fyn mutants showed a striking retardation in the rate of kindling. Once the kindled state was established in fyn mutants it remained stable. This implicates a Fyn-dependent biochemical pathway in the induction but not the maintenance of normal amygdala kindling. fyn is the first gene identified to be required for normal epileptogenesis.

Amygdala↗

PubMed1994

B-50/GAP-43 expression by the olfactory receptor cells and the neurons migrating from the olfactory placode in embryonic rats.

B-50/GAP-43 is a growth-associated phosphoprotein that is commonly expressed in all developing neuronal systems. Using an immunocytochemistry approach, we have investigated the expression of this protein in the rat olfactory system during embryogenesis and neonatal development with a particular emphasis on the early developmental stages of the olfactory placode. Data show that already at embryonic day 12 (E12), a strong B-50/GAP-43 immunoreactivity was detected in few olfactory receptor cells well-recognizable by their positive short neuritic processes. The B-50/GAP-43 expression in the placodal epithelium thus appeared to coincide with the onset of neurite outgrowth. From E13 onwards, there was a rapid increase in the number of B-50/GAP-43-positive olfactory neurons and from E18, the protein was strongly expressed by nearly all neurons. In addition, results clearly demonstrate that as early as E13, B-50/GAP-43 was strongly expressed by many migrating cells which were seen leaving the pit epithelium in association with the first olfactory axons that penetrated the nasal mesenchyme. Many immunoreactive cells were also observed in the presumptive olfactory nerve layer. Experiments of double-labeling showed that B-50/GAP-43-immunostained migrating cells were also stained with anti-neuron-specific enolase (NSE). This confirms the neuronal nature of these early labeled migrating cells. The progressive disappearance of migrating neurons noted during the late stages of embryonic development is discussed in relation with their possible function in the early stages of development of the peripheral olfactory system.

Animals↗

PubMed1993

The CVS strain of rabies virus as transneuronal tracer in the olfactory system of mice.

The sequential distribution of transneuronally infected neurons was studied in the olfactory pathway of mice after unilateral inoculation of the challenge virus standard (CVS) strain in the nasal cavity. A first cycle of viral multiplication was observed in a subpopulation of receptor cells scattered in the main olfactory epithelium and in the septal organ. No viral spread from cell body to cell body was reported even in later stages of infection. The second round of viral replication which took place in the ipsilateral main olfactory bulb at 2 and 2.5 days post-inoculation (p.i.), involved second order neurons and periglomerular cells, known to be directly connected with the axon terminals of receptor cells. Also reported as a result of a second cycle of viral replication, was surprisingly the spread of CVS at 2 and 2.5 days p.i. in bulbar interneurons located in the internal plexiform layer and in the superficial granule cell layer, as well as that of 2 ipsilateral cerebral nuclei, the anterior olfactory nucleus and the horizontal limb of the diagonal band. From day 3, a rapid spread of CVS was suggested by detection of virus in all ipsilateral direct terminal regions of the second order neurons and in most tertiary olfactory projections. The locus coeruleus, a noradrenergic nucleus which sends direct afferents to the olfactory bulb, never appeared immunoreactive. In spite of a certain inability of CVS to infect some neuron types, the virus appears relevant to provide new information regarding the complex network of olfactory-related neurons into the CNS.

Afferent Pathways↗

PubMed1993

Polypropylene pellets as an inexpensive reusable substitute for milk in the Morris milk maze.

A new inexpensive opaquing agent for the Morris milk maze is described. Small light-weight polypropylene pellets that float on the surface of the water were used to eliminate visual cues about the location of the hidden platform without impeding swimming or the use of distal spatial cues. Results obtained using the pellets are identical to those obtained with milk powder as an opaquing agent. An automatic tracking system works as well with the pellet as with the milk version of the maze.

Animals↗

PubMed1993

Effects of chronic low-level copper exposure on ultrastructure of the olfactory system in rainbow trout (Oncorhynchus mykiss).

This study investigated the effects of a chronic exposure to a low level of copper on cell populations of the olfactory system in yearling rainbow trout. Fish were sacrificed after 15, 30 and 60 days of copper exposure. Transmission electron microscopy was used to describe the sequence of subcellular changes occurring in three tissues, the sensory epithelium, the olfactory nerve and the olfactory bulb. Data show that a 15-day exposure to 20 micrograms/l of copper causes specific degeneration of all mature receptor cells as well as numerous immature neurons. Moreover, degenerating receptor cells exhibited morphological features of a cell death by apoptosis. After 30 days, and more specifically after 60 days of exposure, numerous clusters of cells were observed in the basal region of the epithelium, suggesting a great mitotic activity in this area. In parallel, an increased number of maturing receptor cells and goblet cells were observed, but no fully mature neurons were noted even after 60 days of exposure. In both the olfactory nerve and the olfactory bulb, the number of degenerating axons and terminals, which was high at 15 days, decreased with time and some process of glomerular reinnervation was detected after 60 days. A reactive hypertrophy of supporting, ensheathing and astrocytic cells was also observed in exposed fish, which demonstrates that these cell types are actively involved in the process of tissue scarring. Even though some signs of neuronal regeneration were reported during the time-course of exposure, indicating some fish acclimation, results raise the question of the olfactory function during such environmental stress.

Animals↗

PubMed1992

Organization of the septal organ projection to the main olfactory bulb in adult and newborn rats.

The septal organ, which is regarded as an olfactory subsystem, is a small patch of sensory epithelium located ventral to the main olfactory sheet on the septal wall of the nasal cavity. The only consensus to date regarding some proper area of projection of this subsystem is that the septal organ projects to the medial aspect of the main olfactory bulb. The purpose of our study was to analyze precisely the topographical organization of the bulbar projection of the septal organ in adult rats and in 3- to 15-day-old rats following WGA-HRP placements at the level of the septal epithelium. Results show that the septal organ projects exclusively to the posterior half of the main olfactory bulb and its projection area is mainly restricted to the ventromedial bulbar aspect. When the septal organ was fully injected, the pattern of bulbar projection was characterized by two types of glomerular labeling: 1) presence of single heavily labeled glomeruli identified as "septal" glomeruli, since they were mainly built up by afferents coming from the septal organ and (2) presence of a thin network of labeled septal fibers distributed in glomeruli which were mainly formed by afferents coming from the main olfactory epithelium. Although the pattern of mucosobulbar projection of the septal organ is already established in newborns, a significant increase in the number of "septal" glomeruli occurs during the first 15 postnatal days. Anatomical data indicate that even if the projection of the septal organ does not appear completely segregated in the olfactory bulb, this projection is not either exactly similar to that of the main olfactory epithelium.

Aging↗

PubMed1992

Nature of the clinical difficulties of first-year family medicine residents under direct observation.

OBJECTIVE: To determine and classify the difficulties of first-year family medicine residents observed during clinical interviews. DESIGN: Retrospective, descriptive study. SETTING: Family practice unit at a teaching hospital. PARTICIPANTS: Forty-seven of the 56 first-year family medicine residents during their 2-month compulsory rotation in ambulatory family medicine, between July 1983 and December 1988, and 4 physicians who supervised the residents. MAIN OUTCOME MEASURE: The residents' difficulties noted on the observation forms. MAIN RESULTS: A total of 1500 difficulties were observed during 194 interviews, an average of 7.7 (standard deviation 5.2) per interview. There were 167 different difficulties, which were classified into seven categories (introduction, initial contract, body of the interview, techniques and organization, interpersonal aspects, final contract and miscellaneous) and 20 subcategories. The 17 most frequently noted difficulties accounted for 40% of the total. CONCLUSIONS: The results constitute a useful starting point for developing a classification of residents' difficulties during clinical interviews. We believe that the list of difficulties is applicable to residents at all levels and in other specialties, especially in ambulatory settings. The list can be used to develop learning materials for supervisors and residents.

Clinical Competence↗

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↗

PubMed1989

Cellular expression of H and B antigens in the rat olfactory system during development.

Developmental expression of H and B antigens in the rat olfactory system was studied from the embryonic day 14 up to the postnatal day 30. The H antigen was detected in the olfactory and vomeronasal epithelia as early as fetal day 14, whereas the B antigen first appeared 2 days later. The anti-H reagent reacted strongly with sensory receptors and weakly with supporting cells in both epithelia, whereas the anti-B reagent was specific for olfactory receptors. In the main olfactory epithelium, the H antigen was expressed from fetal day 19 by most of the receptor cells, whereas the B determinant was expressed from fetal day 16 to postnatal day 3 by only a few neuroreceptors mostly located near the epithelial surface. After the postnatal day 3, B positive neurons increased in number from the periphery toward the deeper mucosal layers and they were distributed over 3/4 of the epithelial thickness in 15- and 30-day-old rats. In the main olfactory bulb, a widespread glomerular B staining with variable binding intensity between adjacent glomeruli was already observed at birth. The vomeronasal receptor cells and their axon terminals in the accessory olfactory bulb exhibited a comparable developmental expression of the B antigen. Results suggest that the B antigen could be regarded as a marker of neuronal maturation of both the olfactory and vomeronasal receptor cells; moreover, its first appearance in the receptor cells might be temporally related to the formation of synapses between receptor axons and deutoneurons in the bulb.

ABO Blood-Group System↗

PubMed1988

Topographical projection of the septal organ to the main olfactory bulb in rats: ontogenetic study.

Using the horseradish peroxidase (HRP) retrograde tracing method, we have studied the topographical organization of the projection of the septal organ to the main olfactory bulb in rats varying in age from 22 fetal days up to 15 postnatal days. For all developmental stages studied, receptor cells of the septal organ had their axons ending in a relatively circumscribed region of the olfactory bulb, which was the posterior ventromedial bulbar aspect. In younger animals, olfactory receptor cells were observed within the epithelial area isolating the septal organ from the olfactory epithelium, whereas this area was reported to be an exclusive respiratory region in adult rats. The complete disappearance of these receptor cells noted in 12-day-old rats was related to some ontogenetic process.

Afferent Pathways↗

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↗