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T L Petit

Publications and source records attributed to T L Petit.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Memory, synaptic plasticity and neurotoxins.

Most neurotoxins induce serious impairments in cognitive or intellectual functioning; therefore, the ability of the individual to learn and remember forms a critical component of neurotoxin assessment. In depth investigations of neurotoxin-induced cognitive deficits have assisted in pinpointing the neural site of toxin activity. However, specific impairments in learning and memory can depend on the developmental stage at which the individual is exposed to the toxin, and certain neurotoxins show cognitive lifespan selectivity. There appears to be a basic sequence of events underlying neural development and information storage, and neurotoxins may disrupt this neuronal sequel critical for the storage or expression of "ancestral" or "environmental" memories. Certain primary rules govern the orderly development of the nervous system; these rules or mechanisms allow the expression of "ancestral memories" concerning neuronal differentiation and primitive behaviors. Following birth, these same mechanisms have been retained in a less robust form to allow learning and information storage, or the retention of "environmental memories." Neurotoxins which disrupt learning and memory capacities appear to interfere in this basic sequence of events, with the specific outcome depending on when during lifespan development the neurotoxin intervenes.

Animals↗
PubMed1989

Synaptic structural plasticity: role of synaptic shape.

Recent research has indicated that synaptic curvature is an important and potentially critical plastic feature of the synapse. Alterations in synaptic shape are related to synaptic function, being found both during maturation and in adulthood following neuronal activation. In this paper we review the evidence supporting synaptic shape as a plastic feature of synaptic structure. We also propose several mechanisms which might underlie these changes in shape. Finally, we suggest the possible functional role of alterations in synaptic curvature, including its potential in altering synaptic transmission efficacy.

Aging↗
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↗
PubMed1988

The neurobiology of learning and memory: elucidation of the mechanisms of cognitive dysfunction.

This paper reviews evidence which suggests that there is a series of events at the synaptic level, beginning with synaptic activation, responsible for the formation of memories. Synaptic use above routine levels activates NMDA receptors which allows calcium influx into the neuron. Calcium appears to trigger changes in synapse and synaptic terminal shape (via cytoskeletal activation), and an increase in synaptic size (via new protein synthesis). New synapses ultimately form either de novo or by splitting, and new dendritic spines and dendritic length is added. Several forms of cognitive dysfunction, such as Downs syndrome, aging and Alzheimer's disease, and exposure to the neurotoxins lead or aluminum appear to involve, at least in part, disruptions in this process. Evidence is reviewed to support the theory that memories may involve alterations in specific sets of synapses located at specific dendritic locations; this theory may explain some of the learning and memory deficits seen in conditions resulting in cognitive dysfunction.

Cognition Disorders↗
PubMed1987

Neocortical synaptogenesis, aging, and behavior: lifespan development in the motor-sensory system of the rat.

Little evidence presently exists on the development and aging of synaptic contacts and their relationship to behavior, particularly in nonvisual brain areas. To investigate this interrelationship, rats at a series of developmental ages [postnatal day 1 (P1) to P90] were initially examined on a battery of motor tasks. The battery, ranging from simple reflexive tests to tests of complex locomotor capacities, consisted of tactile-induced forelimb placing, chin-induced placing, body righting, climbing an inclined plane, traversing a narrow beam, and keeping up with a revolving wheel. Following completion of the behavioral testing, the animals, together with an additional group of aged (28- to 29-month-old) rats, were killed and their motor-sensory cortex was removed, stained with osmium tetroxide or ethanol phosphotungstic acid (EPTA), and examined under electron microscopy for density of synaptic contacts. Simple motor abilities such as tactile-induced placing was present by the end of the first postnatal week, with locomotor performance reaching a mature level by the end of the third postnatal week, and intermediate task abilities maturing within this range. Paralleling the development of complex locomotor skills was a sharp increase in synaptic density in the molecular layer of the motor-sensory cortex, commencing in the second postnatal week and peaking at P30. After P30 there was a sharp decline in synaptic density as well as a decline in performance on some motor tasks, although these two functions seemed to be occurring independently. There was a continued, but less dramatic synaptic loss evident in the aged rats.

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↗
PubMed1986

Differential survival of fetal and adult neurons and non-neuronal cells exposed chronically to ethanol in cell culture.

Neural cell cultures of dissociated dorsal root ganglia (DRG) were used to investigate the effect of chronic ethanol exposure on the differential survival of fetal and adult neurons and non-neuronal cells. After 12 days of culture in ethanol (20 DIV), counts were made of both neurons and non-neural cells. Unexpectedly, the adult neurons showed a slightly greater degeneration with increasing ethanol than fetal neurons; the adult and the fetal neurons had LD50s of 1.78 and 2.08 gm% respectively. In contrast, for the non-neuronal cells the differential response was reversed; the fetal non neuronal cells were more affected than the adult non neuronal cells with LD50s of 0.7 gm% and 0.94 gm% for fetal and adult non-neuronal cells respectively. Also independent of developmental stage, the non-neuronal cells were 2 to 3 times more sensitive (in terms of survival) to increasing ethanol than the neurons. Electron microscopic examination suggested an increased amount of lipofuscin and dilated endoplasmic reticulum in the adult neurons exposed to ethanol. The possible significance of the results to fetal alcohol syndrome (FAS) is discussed.

Age Factors↗
PubMed1986

The effects of lead exposure on field potentials of CA3 pyramidal cells from mossy fiber stimulation in rat hippocampus.

Previous anatomical evidence indicates that lead (Pb) alters development of the hippocampus and electrophysiological data suggest that Pb interferes with several neuronal systems outside the hippocampus. The present research was undertaken to examine the possibility that exposure to Pb early in development induces electrophysiological alterations in field potentials of CA3 pyramidal cells. Rat pups were exposed to Pb for the first 25 days of age via maternal milk. During this period, dams were fed diets containing either 4% PbCO3 or a Na2CO3 control diet. At 39-54 days of age, 15 sec trains of 20 Hz electrical stimuli at near-maximal intensities were delivered to the dentate granule cells of anaesthetized rats. No significant differences between Pb-treated and control animals were detected for the evoked responses during or after the stimulus trains. However, spreading depression was observed in a greater proportion of Pb-treated animals and more frequently within single Pb-treated animals than in controls. Repetitive bursting, which followed termination of most 20-Hz trains, was significantly longer for Pb-treated animals. The duration of single bursts and the interval between bursts in a given episode were also longer in Pb-treated animals. These data support the hypothesis that developmental Pb exposure alters the electrophysiological properties of CA3 pyramidal cells.

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↗
PubMed1985

Establishment of status epilepticus by limbic system stimulation in previously unstimulated rats.

A syndrome of convulsive status epilepticus developed in 4 of 18 rats which had been treated with continuous sine wave stimulation incrementally raised to 40 microA through limbic system electrodes. The syndrome was characterized by recurrent behavioral seizures, continuous EEG spiking, and marked neuropathology. In three other animals, the stimulation treatment produced a syndrome of nonconvulsive status epilepticus manifested by an electrophysiologic record of continuous seizure activity, without accompanying tonic-clonic movements. The poststimulatory effect was correlated with the animals' response to the stimulation, and was independent of whether the electrode was positioned in the hippocampus or amygdala. If an animal developed repeated convulsive seizures during the stimulation, such seizures were likely to persist after the stimulation offset. These results indicate that persistent limbic system activation can produce a syndrome of recurrent seizures similar to that caused by either neurotoxic drugs or by limbic system activation in kindled rats.

Amygdala↗
PubMed1985

Postnatal lead exposure and the cholinergic system.

Previous reports have suggested that the behavioral effects of early lead (Pb) exposure may be due to an underlying deficiency in cholinergic function. To further examine 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 (High Pb), 0.4% PbCO3 (low Pb) or a Na2CO3 control diet throughout this period. Beginning at 65 days of age, animals were tested on behavioral tasks sensitive to both Pb exposure and cholinergic deficiency. Exposure to both levels of Pb impaired passive avoidance acquisition and produced lower rates of spontaneous alternation. Pb, however, had no clear effects on open field activity. The cholinergic agonist physostigmine (0.05 and 0.075 mg/kg) did not affect the behavior of control animals on any task, but in both Pb exposed groups physostigmine improved passive avoidance acquisition, increased the rate of spontaneous alternation and lowered open field activity scores. The cholinergic antagonist scopolamine (0.4 mg/kg) impaired passive avoidance acquisition, lowered the rate of spontaneous alternation and increased open field activity scores in control animals. Consistent with behavior characteristic of an inverted U shaped response curve, scopolamine (0.2 and 0.4 mg/kg) improved passive avoidance acquisition in both Pb exposed groups and decreased open field activity scores in the High Pb group. In all cases, the behavioral response of the Pb exposed animals may be interpreted as responses characteristic of cholinergically deficient animals. These results thus provide further evidence for cholinergic system involvement in the behavioral changes observed following early exposure to Pb.

Animals↗