Search PubMed⌕ Search

Biomedical subjects

J C LeBoutillier

Publications and source records attributed to J C LeBoutillier.

18 recordsLinked to original sources
PubMed1998

The degree of potentiation is associated with synaptic number during the maintenance of long-term potentiation in the rat dentate gyrus.

There is a considerable degree of variation in the amount of potentiation induced in different animals following the induction of long-term potentiation (LTP). This variation provided us with the opportunity to determine what types of synaptic changes were dependent upon the degree of induced potentiation. To examine possible 'degree of potentiation' effects on synapses, we conducted a multiple regression analysis examining the relationship between the degree of potentiation in LTP animals and a series of synaptic structural measures. We examined synapses in the middle third of the molecular layer (MML) of the rat dentate gyrus following repeated high frequency tetanization of the perforant path. LTP was induced over a 4 h period, and the animals were sacrificed 24 h after the final stimulation. Synapses from the ipsilateral inner third of the dentate molecular layer (IML) and from implanted only animals were also examined for comparison. Ultrastructural quantification included the total number of synapses per neuron, synaptic curvature, the presence of synaptic perforations, and the maximum length of the synaptic apposition. The only structural change that was significantly associated with the degree of potentiation was a positive correlation between the degree of LTP and the number of synapses per neuron. Therefore, synaptic number, while not appearing to be significantly associated with the induction of LTP, appears to be important for the degree of LTP expressed.

Animals↗
PubMed1997

Effect of chronic administration of NMDA antagonists on synaptic development.

The current research assessed the role of the N-methyl-D-aspartate (NMDA) receptor in developmental synaptic plasticity. This was accomplished by quantitative analysis of synaptic number and morphology following pharmacological manipulation of NMDA receptor activity using either the competitive antagonist 2-amino-5-phosphonovaleric acid (APV) or the noncompetitive antagonist phencyclidine (PCP). In the first group, 15-day-old male Long-Evans rats were implanted with osmotic minipumps, which administered 50 mM APV or vehicle at a rate of 0.5 microliter per h into the subjects' occipital cortex for 14 days. At age 30 days (P30), the rats were sacrificed and their occipital neocortices were examined. A second group of rats was given subcutaneous injections of 10 mg/kg PCP or vehicle once daily beginning on P5 for a period of 15 days, and was sacrificed on P20. To determine the effects following withdrawal from long-term NMDA antagonism, a third group of animals was given the same PCP injection routine until P20, but was sacrificed on P21, P26, P36, and P56. Developmental administration of APV was associated with a decreased molecular layer depth and estimated total number of synapses. Similarly, PCP induced a reduction in brain weight, molecular layer depth, and estimated total number of synapses. Withdrawal from NMDA antagonism was initially associated with similar results, i.e., reduced brain weight, cortex depth, synaptic density, and estimated total number of synapses, along with an increase in synaptic length. By P36, however, there was a transitory rebound associated with increased molecular layer depth and estimated total number of synapses. These results support the suggestion that NMDA receptor activation is integral to naturally occurring developmental synaptogenesis, and underscore the importance of NMDA receptor involvement in the process of synaptic plasticity.

2-Amino-5-phosphonovalerate↗
PubMed1994

Neural development following NMDA administration in the rat: an electron microscopic examination of the occipital neocortex layer I.

Recent research has suggested that the N-methyl-D-aspartate (NMDA) receptor plays a role in numerous activity dependent models of synaptic plasticity. The current research attempted to determine whether chronic activation of the NMDA receptor could induce alterations in synaptic development. An examination of acute NMDA toxicity indicated that rats become increasingly resistant to NMDA over development. Male rats aged 8 days were administered one, 1/10 LD50, SC injection of either NMDA or saline vehicle every 8 h until 18 days of age and were sacrificed 2 days later. Chronic administration of NMDA produced no changes in body or brain weight, the length of synaptic contacts, or the number of synapses per unit area in the neocortical molecular layer. There was a significant 10% increase in the depth of the occipital cortex molecular layer, yielding a 15% increase in the estimated total number of synapses within that area. These results suggest that activation of the NMDA receptor is capable of altering certain aspects of neural development, while other components are not affected.

Aging↗
PubMed1993

Structure and plasticity of newly formed adult synapses: a morphometric study in the rat hippocampus.

Increasing evidence suggests that synaptic structure represents a plastic feature of the neuron, although the plastic nature of newly formed and existing adult synapses has not yet been fully characterized. Following ipsilateral entorhinal cortical lesions, the rat dentate gyrus offers an excellent model for studying synaptogenesis and plasticity in the adult central nervous system. Unilateral entorhinal lesions were performed in young adult male rats. Synaptic counts and structural features were quantified at 3, 6, 10, 15, and 30 days post-lesion. The lesions resulted in an 88% synaptic loss in the denervated dentate middle molecular layer, which was followed by a period of rapid synaptogenesis. Synaptic element size decreased during the period of maximal synaptogenesis, which was associated with a peak in the presence of non-vesicular and perforated synapses. Following this period, synapses showed a gradual increase in the size of their pre- and postsynaptic elements. These data support the suggestion that newly formed adult synapses have smaller synaptic components than existing adult synapses (resembling synapses seen during development), and increase in size over time with usage. The results are discussed in terms of synaptic structural development and plasticity in the adult central nervous system.

Animals↗
PubMed1992

Altered sensitivity to NMDA following developmental lead exposure in rats.

Early Pb exposure is known to disrupt the development of the hippocampus and result in deficits in learning and memory capacities and altered seizure susceptibility. The excitatory amino acid, NMDA, is found in high concentrations in the hippocampus and has been implicated in learning and memory functions and seizure activity. Rat pups nursed mothers exposed to high (4%), moderate (0.4%), or low (0.05%) levels of PbCO3 in their diet, or a Na2CO3 control diet from postnatal day 1 (P1) to P25. Rat pups were injected with varying doses of NMDA on P15 or P25. Control animals showed a characteristic slowly developing response to NMDA, usually including tail twitches and wet dog shakes at approximately 10 and 40 mg/kg at P15 and P25, respectively, with status epilepticus and death occurring at 40 and 80 mg/kg. Lead-exposed animals displayed an altered sensitivity to NMDA, with high and medium Pb animals showing the onset of behavioral signs and death at lower NMDA doses, the degree of which being dependent on the level of Pb exposure. Low Pb-exposed animals showed a more variable and attenuated response to NMDA. The data are discussed in terms of the possible mechanisms of Pb neurotoxicity.

Animals↗
PubMed1991

Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: an electron microscopic study in the occipital cortex of postnatal rats.

The N-methyl-D-aspartate (NMDA) receptor has been widely implicated in numerous activity-dependent models of neural plasticity, learning, and memory. The formation of new synapses is a major assumption of the neural basis of learning. The current research was conducted to determine whether NMDA receptor activation could induce synaptic formation and, if so, whether this ability would mirror developmental changes in NMDA receptors. Rats at various developmental ages were given a single intraperitoneal injection of NMDA and sacrificed at various brief postinjection intervals (0.5-2 hr). The rats showed an age-dependent decline in the behavioral response to NMDA, as evidenced by reduced seizure activity and duration. Quantitative electron microscopic observations on the molecular layer of the occipital cortex, an area rich in NMDA receptors, revealed a transient increase in the length of postsynaptic thickenings in 17- and 35-day-old animals, appearing within 0.5 hr of injection. At 1 and 2 hr postinjection, an increase in synaptic density (number of synapses) was observed in 8-day-old animals. These results provide evidence that NMDA administration alone is capable of rapidly inducing alterations in synaptic structure and the formation of new synapses, underscoring the importance of the NMDA receptor in synaptogenesis and synaptic structural plasticity.

Aging↗
PubMed1990

Quantifying synaptic number and structure: effects of stain and post-mortem delay.

Current research indicates the importance of synaptic number and structure in plastic processes such as development, learning and memory, and aging. As such, the examination of these neural features has become an important factor in research on human conditions such as mental retardation, aging and Alzheimer's disease. Synaptic research in human tissue typically involves delayed post-mortem fixation, therefore the current research was designed to examine the effect of post-mortem delay on synaptic number and structure in tissue stained with either routine osmium lead citrate/uranyl acetate (osmium) or ethanol phosphotungstic acid (EPTA). Results indicate that synaptic density shows either a gradual decline (EPTA) or an initial marked drop followed by a plateau (osmium) up to 10-15 h post-mortem depending on the stain used. The number of synaptic vesicles per synapse also undergoes a gradual decline. Measures of synaptic structure were more stable, with the primary change being an initial increase in the cross-sectional length of the synapse. Maximal height of the pre- and postsynaptic dense elements were not affected by post-mortem delay. The EPTA stain gave the best estimates of synaptic parameters with short post-mortem delays. These results indicate that different synaptic measures (and stains) show different responses to post-mortem fixation delay, and that experimental or statistical methods must be used to control for post-mortem effects.

Animals↗
PubMed1989

Synaptic structural plasticity following repetitive activation in the rat hippocampus.

The morphological effects of repetitive neuronal activation following systemic kainic acid administration were examined in hippocampal CA1 stratum radiatum synapses. Sporadic activation of CA3 and CA1 neurons began approximately 15-25 min after kainic acid administration, which was followed at 1-2 h by repetitive ictal firing until the completion of the experiments at 4 hr. Synaptic density in the CA1 region increased following stimulation, reaching significance at the earliest time period examined, approximately 5-15 min postactivation. There was an initial increase and then a decline in frown (and then flat)-shaped synaptic subtypes, with an ultimate increase in smile-shaped synapses. This pattern is consistent with either a change in synapses from frown to smile shaped or a selective gain/loss of synaptic subtypes. There was also an increase in the size of smile-shaped synapses, but a decrease in the size of frown synapses. By 4 h there was a decline in most indices of synaptic morphology, suggesting that the stimulation had become cytotoxic. These results indicate that the number and morphology of synapses and synaptic subtypes can be modified with relatively short periods of repeated use and suggest their potential role in activity-dependent phenomenon such as information storage and epilepsy.

Animals↗
PubMed1988

The pattern of dendritic development in the cerebral cortex of the rat.

The pattern of dendritic development of layer V pyramidal cells in the neocortex of the rat was studied using a variety of quantitative techniques in an attempt to determine what rules govern dendritic differentiation. Animals were sacrificed on postnatal days (P) 1, 3, 5, 7, 10, 15, 20, 25, 30 and 60, their brains impregnated with the rapid Golgi technique, and cells from the sensorimotor cortex examined for maximal apical and basilar dendritic field, number of dendritic branches at 20 micron intervals from the cell body, number of apical and basilar branch types (branching order), length of dendritic branch segments, and dendritic spine density. Primary dendrites are formed early in development, with no new ones formed after P7-10. Once a dendritic segment has bifurcated, all further development appears to occur at the tip, i.e. the trunk does not seem to undergo additional elongation, and new branches do not appear to form from the trunk. There is a plateau in dendritic differentiation close to the cell body after approximately P20; however, there is a continued increase in the length of terminal dendritic branches in the distal portions of the dendritic field into adulthood. During early development, dendrites bifurcate on reaching approximately 20-30 microns; however, during adulthood additional length is added to terminal dendrites without branching. Dendritic spines increase dramatically early in development, and then decline on proximal dendrites but continue to increase on terminal branches into adulthood. These results suggest that the terminal portion of the dendritic field remains plastic into adulthood, and that during development several general rules govern the pattern of dendritic differentiation.

Aging↗
PubMed1987

Synaptic structural changes during development and aging.

Although a great deal is known about the development of synaptic number, comparatively little is known about the effects of development, and particularly aging, on the structure of the synapse. The present study examined synaptic structure in the molecular layer of the motor-sensory neocortex during early development (postnatal days (P) 1, 3, 5, 7, 10, 15, 20, 30), adulthood (P60, 90), and old age (28 months). Tissue was stained with osmium tetroxide (osmium) or ethanol phosphotungstic acid and the following synaptic characteristics were quantified: (1) presynaptic element length, area, thickness, maximal projection height and smoothness, and number and size of vesicles adjacent to the presynaptic element; (2) postsynaptic element length, area, and thickness; and (3) cleft width. There is an early developmental increase in synaptic element length, followed by an increase in thickness into adulthood. During development the height and width of the presynaptic dense projections increase, after which they remain stable. While the number of adjacent synaptic vesicles increases throughout the lifespan, there is a parallel decrease in their size. During the period of rapid synaptogenesis in this brain region there are no decreases in any of the synaptic structural parameters examined, indicating that newly generated synapses are either formed the same size as the existing mature synapses, or are extremely plastic and grow very rapidly. Unlike age-associated changes in synaptic number, no changes were found in synaptic structure during aging.

Aging↗
PubMed1986

Zinc deficiency in the postnatal rat: implications for lead toxicity.

Zinc (Zn), an essential element in the diet of mammals, appears to have a high affinity for the hippocampus during development, particularly the mossy fiber pathway (MFP). Lead (Pb) competes at several physiological levels with Zn, and is also selectively sequestered in the MFP. It has been suggested that Pb might exert its neurotoxic effects by displacing Zn and disrupting its functioning in the hippocampus. This study was conducted to address this possibility by examining hippocampal structure and function in perinatally Zn-deprived animals, and comparing the results with those previously observed under identical conditions in Pb-exposed rats. From postnatal day 1 (P1) to P25, Long-Evans hooded rat pups and their mothers were placed on a Zn deficient or control diet. On P25, weight-matched pairs of animals were selected for morphometric evaluation of the MFP following Timm's silver sulfide staining; no differences between groups were observed. Animals were tested at maturity in three behavioral tasks considered sensitive to hippocampal dysfunction. Zn deficiency produced no significant alterations in open field activity levels or passive avoidance performance; however, it did induce significantly reduced rates of spontaneous alternation. These results indicate few neurobehavioral similarities between Pb exposed and Zn deficient animals.

Animals↗
PubMed1985

Neurobehavioral development following aluminum administration in infant rabbits.

Aluminum (Al) is known to be a neurotoxic agent in some species, inducing neurofibrillary tangles, dendritic atrophy, and behavioral deterioration, and has been implicated as a possible agent in human Alzheimer's disease and dialysis dementia. This study was conducted to assess the neurotoxic effects of Al in infant rabbits, and to compare the effects to those previously observed to follow exposure in the adult animal. Aluminum tartrate (2 microM) or physiologic saline was injected into the right lateral ventricle of 2-day-old (day P3) New Zealand white rabbits. The animals were trained in a step-down active avoidance task on P12 and retested 1 day later. They were killed on P20, and their hippocampal CA1 pyramidal cells examined for neurofibrillary tangles or prepared with the rapid Golgi stain for an examination of dendritic development. Additional animals were similarly infused with 1 or 3 microM Al for qualitative and some quantitative observations. No overt neurologic signs were observed in the 1- or 2-microM groups, however, most of the 3-microM group died between P10 and P20. Although there were no significant differences between the 2-microM and control animals on either learning or retention of the active avoidance task, deficits in retention of the task were observed in the 3-microM group. Neurofibrillary tangles in CA1 pyramidal cells were observed with dosages of 1 microM and higher. In the 2-microM group, the pattern of dendritic arborization in CA1 pyramidal cells was consistent with that expected for cells retarded in their development. These results have implications in terms of developmental differences in the neurobehavioral effects of Al.

Aluminum↗
PubMed1984

Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex.

Postmortem tissue was obtained from six normal and four Down's syndrome brains ranging in age from 12 to 40 weeks postconception. Tissue was processed for electron microscopy using routine osmium and EPTA staining procedures, and to examine synaptic development, photomicrographs were systematically taken throughout the molecular layer of the sensorimotor neocortex. The number of EPTA-stained synapses were consistently greater than the number of osmium-stained synaptic contacts. A progressive increase in synaptic density throughout the range of ages examined was observed for both normal and Down's syndrome tissue. There was also an increase with developmental age in apparent measures of synaptic maturity, e.g., an increased ratio of mature to primitive contacts and asymmetrical to symmetrical contacts. In normal tissue, pre- and postsynaptic membrane lengths were observed to increase with the ages studied, whereas synaptic membrane widths appeared to attain mature values by 29 weeks postconception. Cleft width remained fairly constant to 28 weeks postconception. Although direct statistical comparisons could not be made, in Down's tissue synaptic parameter development was generally less consistent and the parameters appeared to be reduced during the later stages of development studied.

Down Syndrome↗
PubMed1983

Development and plasticity of the hippocampal-cholinergic system in normal and early lead exposed rats.

A review of previous evidence suggested the possibility of a functional association between the effects of early lead (Pb) exposure, hippocampal damage and cholinergic deficiency. To further assess this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Dams were fed either 4.0% PbCO3 or a Na2CO3 control diet throughout this period. At 30 and 115 days of age, the brains of Pb and control animals were processed for acetylcholinesterase histochemistry. Morphometric evaluation of the molecular layer of the hippocampal dentate gyrus indicated that while absolute increases in the dimensions of the afferent systems to the hippocampal dentate gyrus are observed between 30 and 115 days of age, no significant rearrangement in the pattern of lamination occurs during this time. No effects of Pb were seen on the development of the cholinergic innervation of this brain region at either of these ages. Unilateral perforant path transections performed on Pb and control animals at 100 days of age indicated reduced cholinergic plasticity in the molecular layer of the hippocampal dentate gyrus of Pb exposed animals, as indicated by AChE histochemistry. These findings indicate that a decrease in neuroanatomical plasticity may be a critical brain mechanism underlying the learning deficits observed following exposure to Pb.

Acetylcholinesterase↗
PubMed1983

Early lead exposure and the hippocampus: a review and recent advances.

A review of previous evidence suggests an association between early Pb exposure and hippocampal dysfunction. This report summarizes recent experiments conducted in both our laboratory and others' examining the effects of early Pb exposure on hippocampal morphological development, and behaviors characteristic of hippocampal dysfunction. Following postnatal Pb exposure marked reductions are seen in general hippocampal development and in the axonal and dendritic development of hippocampal dentate granule cells. Correlated with these neuroanatomical changes are Pb induced behavioral changes which show numerous similarities to those behavioral changes seen following damage to both the adult and developing hippocampus. These observations thus support the suggestion that the hippocampus may play a critical role in mediating many of the behavioral changes observed following early Pb exposure, as well as indicate that the hippocampus may serve as an excellent model system for further examining the neurobehavioral effects of Pb. However, as other brain areas are also clearly effected by Pb, alternative explanations for these lead induced behavioral changes are also discussed.

Acoustic Stimulation↗