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P J Morgane

Publications and source records attributed to P J Morgane.

At least 19 recordsLinked to original sources

Effects of an every other day rapid kindling procedure in prenatally protein malnourished rats.

Prenatally protein (6/25) rats have been reported to require significantly more stimulations to attain a stage 5 seizure than well-nourished controls (25/25) when using either a traditional or rapid every day, kindling procedure. In the present study, a rapid kindling procedure was utilized where both prenatally malnourished and control rats received every other day perforant path kindling (50 Hz, 10 s train) 12 times a day at 5-min intervals. Using this procedure, stage 5 seizures and a fully state were attained in both nutritional groups at approximately the same rate. It is postulated that it is the every other day component of the present procedure which overcomes seizure-induced inhibition in the 6/25 subjects, thereby allowing them to attain stage 5 seizures at the same rate as controls.

Animal Nutritional Physiological Phenomena

Distribution of dopaminergic fibers and neurons in visual and auditory cortices of the harbor porpoise and pilot whale.

The distribution of putative dopaminergic fibers in two sensory cortical areas in the brain of the harbor porpoise (Phocoena phocoena) and pilot whale (Globicephala melaena) was analyzed at the light and electron microscopic levels using tyrosine hydroxylase (TH) immunohistochemistry. The quantitative analysis of the distribution of labeled fibers demonstrates that the primary visual cortex located in the lateral gyrus and entolateral sulcus contains a denser dopaminergic innervation than the auditory cortex within the posterior portion of the presylvian gyrus. In both areas, TH-immunoreactive fibers are densest in layer I, while layers IIIab and VI have intermediate densities and layers II and IIIc-V have the lowest fiber counts. Layer I is characterized by the presence of very thick TH-immunoreactive fiber populations, in addition to the thin and varicose fiber plexus observed throughout the cortical layers. Electron microscopic analyses demonstrated that some of these thick fibers represent the dendrites of TH-immunoreactive neurons located in the deep portion of layer I. The patterns observed in the present study suggest that the dopaminergic projections to the neocortex in whales have a different organization than in terrestrial mammals, particularly rodents and primates. These differences may reflect the fact that during evolution, the cetacean neocortex has retained many of the cytoarchitectonic features that are usually observed only in proisocortical regions in progressive terrestrial mammals.

Animals

Quantitative analysis of long-term potentiation in the hippocampal dentate gyrus of the freely-moving 15-day-old rat.

The magnitude and duration of long-term potentiation (LTP) of perforant path/dentate granule cell synapses was examined in freely moving rats beginning at 15 days of age. Measures of dentate granule cell population EPSP slope and population spike amplitude (PSA) obtained before and after tetanization were used to evaluate the level of LTP. Tetanization resulted in significant enhancement of both the population EPSP slope (approximately +75%) and PSA (approximately +40%) measures. This enhancement was maintained without significant change for 18 h, after which both measures began a steady and continuous rise. Daily input/output response measures from age-matched nontetanized animals were used to factor out enhancement related to normal development. Under this schema, tetanization-induced enhancement of both EPSP slope and PSA measures decayed slowly, beginning 18-24 h after tetanization, returning to baseline 5 days after tetanization. Enhancement obtained from 90-day-old animals decayed to baseline 24 h after tetanization. The longer duration of LTP obtained from preweanlings is discussed with regard to the development of inhibitory systems modulating granule cell excitability.

Animals

Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat.

The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of 1) the slope of the population excitatory postsynaptic potential (EPSP), and 2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day-old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Prenatal malnutrition and development of the brain.

In this review, we have summarized various aspects as to how prenatal protein malnutrition affects development of the brain and have attempted to integrate several broad principles, concepts, and trends in this field in relation to our findings and other studies of malnutrition insults. Nutrition is probably the single greatest environmental influence both on the fetus and neonate, and plays a necessary role in the maturation and functional development of the central nervous system. Prenatal protein malnutrition adversely affects the developing brain in numerous ways, depending largely on its timing in relation to various developmental events in the brain and, to a lesser extent, on the type and severity of the deprivation. Many of the effects of prenatal malnutrition are permanent, though some degree of amelioration may be produced by exposure to stimulating and enriched environments. Malnutrition exerts its effects during development, not only during the so-called brain growth spurt period, but also during early organizational processes such as neurogenesis, cell migration, and differentiation. Malnutrition results in a variety of minimal brain dysfunction-type syndromes and ultimately affects attentional processes and interactions of the organism with the environment, in particular producing functional isolation from the environment, often leading to various types of learning disabilities. In malnutrition insult, we are dealing with a distributed, not focal, brain pathology and various developmental failures. Quantitative assessments show distorted relations between neurons and glia, poor formation of neuronal circuits and alterations of normal regressive events, including cell death and axonal and dendritic pruning, resulting in modified patterns of brain organization. Malnutrition insult results in deviations in normal age-related sequences of brain maturation, particularly affecting coordinated development of various cell types and, ultimately, affecting the formation of neuronal circuits and the commencing of activity of neurotransmitter cell types and, ultimately, affecting the formation of neuronal circuits and the commencing of activity of neurotransmitter systems. It is obvious that such diffuse type "lesions" can be adequately assessed only by interdisciplinary studies across a broad range of approaches, including morphological, biochemical, neurophysiological, and behavioral analyses.

Animals

Calretinin-immunoreactive neurons in the primary visual cortex of dolphin and human brains.

A new class of gamma-aminobutyric acid (GABA)ergic neurons immunoreactive to the calcium-binding protein calretinin (CR) was demonstrated in primary visual cortices of the bottlenose dolphin (Tursiops truncatus) and humans (Homo sapiens). Comparative analysis revealed several differences between dolphin and human visual cortex in the laminar distribution of CR-positive perikarya, although general typology of the immunoreactive CR-positive neurons was similar in both species. Thus, in both human and dolphin primary visual cortex almost all CR-positive neurons are non-pyramidal, either fusiform or bipolar cells, oriented with their long axis along the radial axis of the cortex. Large multipolar stellate cells were also observed in layers I and VI. The CR-positive neurons in the dolphin visual cortex are concentrated almost exclusively in layer I and, to a lesser extent, in layer II. In all other layers (IIIa, b, IIIc/V and VI) of the dolphin visual cortex CR-positive neurons were only rarely seen. In the human primary visual cortex CR-positive neurons are located mainly in layers II, III and IVa, b, c, with considerably lower densities of these cells observed in layers V and VI. CR-positive neurons in layer I of the human visual cortex are represented by Cajal-Retzius horizontal cells, whereas no such cells were seen in layer I of the dolphin neocortex. The numerical density of CR-positive neurons in the dolphin primary visual cortex is significantly lower than in the area of cortex in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The primary auditory cortex in cetacean and human brain: a comparative analysis of neurofilament protein-containing pyramidal neurons.

To extend our investigation of the anatomy of sensory systems in highly adapted aquatic and terrestrial mammals, we have analyzed the distribution of a particular population of efferent neurons in the cetacean and human primary auditory cortex using an antibody to non-phosphorylated neurofilament protein (SMI32). The neurofilament protein triplet is differentially distributed within neuronal subpopulations in the primate and cetacean neocortex. In primates, it appears that the somatodendritic domain of a subset of pyramidal neurons furnishing specific corticocortical connections contains high concentrations of neurofilament protein. In the human primary auditory cortex these neurons are located in layers III, V and VI, whereas in cetaceans they are concentrated almost exclusively in the cortical efferent layer IIIc/V. Previous analyses have shown that SMI32 immunoreactivity in the cetacean neocortex is uniformly distributed among functionally different areas, while in human neocortex, the distribution of SMI32-positive neurons exhibit a high degree of regional and laminar specialization that is correlated with the functional and anatomical diversity of the cortical areas. In addition, the overall distribution of SMI32-immunoreactive neurons in the cetacean neocortex is comparable to that observed in paralimbic areas of the human, suggesting that the cetacean neocortex has retained many features of phylogenetically older cortical regions.

Animals

Prenatal protein malnutrition alters behavioral state modulation of inhibition and facilitation in the dentate gyrus.

We have examined the effects of prenatal protein malnutrition on interneuronally mediated inhibition and facilitation in the dentate gyrus of the rat using the paired-pulse technique. Field potentials were recorded in the dentate gyrus in response to paired stimuli delivered to the perforant path. The paired-pulse index (PPI) was used as a measure of the net short-term facilitation or interneuronally mediated inhibition effective at the time of the paired-pulse test and was computed by dividing the amplitude of the second population spike (p2) by the amplitude of the first population spike (p1). PPIs were classified according to p1 in order to compare PPIs between behavioral states and dietary treatments since population spike amplitudes in the dentate gyrus vary in relation to behavioral state. Testing was performed during 4 behavioral states: slow-wave sleep (SWS), paradoxical sleep (REM), immobile waking (IW) and exploratory locomotion (AW) using interpulse intervals (IPI) from 20 to 400 ms. The magnitude and duration of interneuronally mediated inhibition was significantly increased in prenatal protein malnourished animals when compared with controls. Paired-pulse tests performed using an IPI of 20 ms under the high p1 (p1 greater than median) condition showed significantly smaller PPIs in prenatal protein malnourished rats regardless of behavioral state. For IPIs greater than 20 ms PPIs were consistently smaller in prenatal protein malnourished rats during SWS and IW. These data indicate that both the magnitude and duration of interneuronally mediated inhibition are increased in prenatally malnourished rats. No consistent diet-related differences were found during AW and REM using IPIs greater than 20 ms because interneuronally mediated inhibition was relatively suppressed during these behavioral states for both dietary groups. There was no consistent behavioral state modulation of paired-pulse facilitation (IPI = 40 to 80 ms) or late inhibition (IPI = 400 ms) in either diet group. In addition, a new relation between PPI and IPI was found under the low p1 (p1 greater than median) condition. During AW the PPIs observed using IPIs of 40 and 50 ms were smaller than those observed using IPIs of 30 and 60 ms. This depression interrupts what is generally considered the "facilitatory" phase of paired-pulse response and may indicate an interaction between perforant path stimulation and hippocampal theta rhythm which is masked when p1 amplitude is high.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance

Effects of prenatal protein deprivation on postnatal development of granule cells in the fascia dentata.

The effect of prenatal protein deprivation on the postnatal development of granule cells in the fascia dentata in the rat was studied at 15, 30, 90, and 220 days of age. The granule cells showed a significant reduction in cell size, decreased number of synaptic spines throughout their dendritic extent, and reduced complexity of dendritic branching in the outer two-thirds of the molecular layer. All of these deficits were present at 15 days and persisted throughout the study (220 days). The least deficits in synaptic spine density occurred at 90 days and in dendritic branching at 30 days. Partial restitution of earlier, more severe deficits was associated primarily with maturational events occurring in the protein deprived rats, whereas later increases in deficits were related primarily to a failure of the protein deprived rats to keep pace with neuronal development occurring in the controls. The present results are similar to those noted in our previous study in this journal of the effect of a low protein diet (8% casein) on these neurons that extended from pregnancy until the time of sacrifice at 30, 90, and 220 days of age (Cintra et al., '90; 532:271-277). Taken together, these two studies suggest that the postnatal adaptation of the granule cells to prenatal protein deprivation is primarily due to events that occur during pregnancy and that the site of predilection for the deficit is their dendrites in the outer two-thirds of the molecular layer of the fascia dentata.

Aging

Effects of prenatal protein malnutrition on kindling-induced alterations in dentate granule cell excitability. I. Synaptic transmission measures.

The effects of prenatal protein malnutrition upon the efficacy of excitatory synaptic transmission at the level of the perforant path/dentate granule cell synapse were examined during development of perforant path kindling in chronically implanted adults rats. Rats born to dams fed a low protein (6% casein) or control protein (25% casein) diet were fostered to lactating dams fed the 25% casein diet 24 h after birth and were maintained on this diet throughout life following weaning. Beginning at 90-120 days of age, animals received daily kindling stimulations applied to the perforant path. Extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to single-pulse stimulation of the perforant path were analyzed to determine the effects of prenatal protein malnutrition on the efficacy of synaptic transmission during the kindling process. Measures used for these analyses included the EPSP slope, an indicator of the level of synaptic drive, the population spike amplitude which is a measure of postsynaptic activation and cellular firing, and the ratio of the population spike amplitude relative to the corresponding EPSP slope value, which was used to evaluate the overall efficacy of synaptic transmission. animals of the 6%/25% diet group were found to have significantly lower afterdischarge thresholds, yet required significantly more daily kindling stimulations to develop generalized motor convulsions (stage 5 seizure) than control animals. Examination of dentate field potentials obtained prior to kindling revealed no significant between group differences in measures of EPSP slope or population spike amplitude. Statistically significant increases in measures of both the population EPSP slope and population spike amplitude were observed in both diet groups 24 h after the first kindled afterdischarge. The degree of increase in both of these measures was significantly greater in animals of the 6%/25% group. Evaluation of input/output measures obtained during kindling revealed a steady increase in the population EPSP slope for both diet groups with animals of the 6%/25% group showing significantly greater levels of enhancement in this measure than controls. Enhancement of population spike amplitudes reached maximal values in animals of the 25%/25% group within the first few kindling stimulations and these levels remained unchanged until the first stage 5 seizure. In contrast, animals of the 6%/25% group showed a continuous increase in the population spike amplitude measure during the entire kindling process. Appearance of the first generalized motor convulsion (stage 5 seizure) resulted in a decrease in population spike amplitudes in both diet groups, with animals of the 6%/25% group showing a significantly greater decrease in this measure than controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging

Effects of prenatal protein malnutrition on kindling-induced alterations in dentate granule cell excitability. II. Paired-pulse measures.

The effects of prenatal protein malnutrition on kindling-induced changes in inhibitory modulation of dentate granule cell activity were examined by analysis of extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to paired-pulse stimulation of the perforant pathway in freely-moving rats. Since we have shown that kindling results in enhanced synaptic transmission at the level of the perforant path/granule cell synapse (see preceding paper), we sought to determine if the kindling process might induce changes in inhibitory modulation of granule cell excitability which could be involved in the slower acquisition of the kindled state we have previously reported in malnourished animals. Beginning at 120-150 days of age, the response of dentate granule cells to paired-pulse stimulation of the perforant path was examined at interpulse intervals (IPIs) ranging from 20-1000 ms. A paired-pulse index (PPI) was constructed based on the mean percent change in population spike amplitudes of the two responses resulting from application of the pulse pair. PPI measures obtained during the kindling process were compared with individual prekindling measures to determine the mean percent change in excitatory/inhibitory modulation of granule cell activity. Significant inhibition of the second population response was apparent at all IPIs tested for both diet groups following the first kindled afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Prenatal protein malnutrition and hippocampal function: rapid kindling.

A stimulation paradigm evoking rapidly recurring seizure activity from the hippocampal dentate gyrus was used to examine perforant path kindling in prenatally protein malnourished adult rats. Biphasic electrical stimulations (50 Hz) of five s duration were applied to the perforant path every five min for one hour over five consecutive days. Behavioral manifestations of seizure activity were assessed using the standard 0-5 scale. Prenatally malnourished rats exhibited significantly fewer convulsive seizures (stage 5) and required significantly more stimulations to attain the first stage 5 seizure than controls. Animals of the malnourished group also exhibited significantly more stage 1 seizures than control animals, indicating a significant retardation in the kindling rate of these animals. Additionally, 3 of the 11 malnourished animals failed to exhibit a single stage 5 seizure during the 60 stimulation test period. These findings parallel previous results reported for prenatally protein malnourished rats using the traditional one stimulation-per-day kindling paradigm and indicate that this rapid kindling paradigm can be effectively used to study the impact of various insults on seizure susceptibility and development in a shortened time frame.

Analysis of Variance

Effects of protein undernutrition on the dentate gyrus in rats of three age groups.

The effect of an 8% casein and a control 25% casein diet on the granule cells in the dorsal blade of the dentate gyrus of the rat hippocampal formation was studied at 30, 90 and 220 days of age. Female rats were fed either an 8% or 25% casein diet 5 weeks prior to conception and the litters were maintained on these respective diets until killed. In rapid-Golgi-impregnated cells, we measured major and minor axes of the soma of the dentate granule neurons, the number of spines on 50-microns segments of proximal, middle and terminal regions of the largest dendrite per granule cell and the number of dendrites intersecting 8 concentric rings 38 microns apart. At all 3 ages studied undernourished rats showed, when compared to controls, significant reductions of the major and minor axes of the somata and significant reductions in the number of spines on dendrites in the middle and terminal dendritic segments. Dendritic branching was significantly reduced in undernourished rats compared to controls in all but the 4th concentric rings, with the greatest effect being seen on the outer 3 concentric rings at 90 and 220 days of age. The location of the deficit in dendritic synaptic spines and the greatest deficit in dendritic branching correspond to the sites of termination of the lateral and medial perforant pathway projection to the dentate gyrus on the terminal and middle dendritic segments of the granule cells. The deficits noted in the granule cells of the dentate gyrus in this study were more severe than those found in our previous studies on the effect of the low protein diet in these same rats on visual cortical pyramidal cells and on the 3 cell types in the nucleus raphe dorsalis and nucleus locus coeruleus.

Analysis of Variance

Effects of prenatal protein malnutrition on perforant path kindling in the rat.

Rats born to dams fed either a 6% (malnourished) or 25% (control) casein diet during gestation were all fostered to lactating dams on the 25% casein diet 24 h after birth and were maintained on this diet throughout life following weaning. At 90-120 days of age electrographic and behavioral responses to electrical kindling of the medial perforant pathway were investigated in animals from both the straight 25% diet (designated 25%/25% for the pre- and postnatal periods) and the dietary rehabilitated (designated 6%/25% casein diet for the pre- and postnatal periods) groups. Animals of the dietary rehabilitated group (6%/25%) were found to: (1) require a significantly lower stimulus intensity to evoke afterdischarge activity in the ipsilateral dentate gyrus; (2) progress through the various behavioral stages of kindling in a markedly different manner from the 25%/25% group, and; (3) require significantly more daily kindling stimulations to attain the full motor convulsive stage indicative of the kindled state. These results indicate that dietary protein rehabilitation at birth is incapable of reversing or significantly ameliorating the effects of gestational protein deficiency on susceptibility to seizure activity and acquisition of the kindled state. These findings indicate that gestational protein deficiency results in long-lasting, if not permanent, changes in neuronal systems in the hippocampal formation which are involved in both the electrographic and behavioral correlates of the kindling process.

Animals

Effects of protein deprivation on pyramidal cells of the visual cortex in rats of three age groups.

The effect of protein deprivation on rapid Golgi impregnated pyramidal neurons in layers II/III and V of the rat visual cortex was studied at 30, 90, and 220 days of age using morphometric methods. In order to mimic human under-nutrition female rats were adapted to either an 8% or control 25% casein diet 5 weeks prior to conception and maintained on these diets during gestation and lactation. The pups were then weaned and maintained on their respective diets. The undernourished rats showed a significant decrease in brain weight only at 90 days, indicating that the protein deprivation had a mild effect on brain development. Correspondingly, the number of significant histological differences between the two diet groups were least at 30 and 220 days of age. The effect of the diet was greater on layer V than on layer II/III pyramids. At 30 days of age the effect of the diet was different on the pyramids of these two cell layers, at 90 days there was a mixture of similar and dissimilar effects, and at 220 days the pyramids of these two cell layers showed only minor differences between the two diet groups. Analysis of age-related changes indicated that the effect of the diet was different on layer II/III pyramids compared to layer V pyramidal cells. These different effects apparently accounted for the progression from a dissimilar effect of the diet at 30 days on the pyramids of the two cell layers to only minor differences between them at 220 days. Further analysis of these age-related changes shows that two prominent effects of protein deprivation are for age-related changes to occur in undernourished rats but not in controls and for age-related changes to be out-of-phase with each other in the two diet groups. From these findings, and a review of similar studies in the literature, we propose that these mechanisms are a prominent effect of undernutrition in the post-weaning period and help account for the unexpected increases in morphometric measurements noted in undernourished rats in this and other studies.

Aging

Ultrastructure of synapses and golgi analysis of neurons in neocortex of the lateral gyrus (visual cortex) of the dolphin and pilot whale.

Qualitative and computerized quantitative analyses of ultrastructural features of synapses in different layers of the primary visual cortex in the dolphin (Stenella coeruleoalba) and the pilot whale (Globicephala melaena) were carried out. Also, Golgi and cytoarchitectonic analyses were performed in the same species of cetaceans and, additionally, in Tursiops truncatus and Phocaena phocaena. It was found that on a synaptic level, as well as in cytoarchitectonic and Golgi features, the neocortex of cetaceans combines evolutionary progressive features and conservative features with a marked prevalence of the latter. Thus, the total number of synapses in visual neocortex in cetaceans is closer to this value in higher Primates. On the other hand, the laminar density of synapses per mm3 is generally the same in all layers in cetacean visual cortex and numerically is close to values found in small lissencephalic brains. Also, the synapse/neuron ratio in the dolphin visual cortex is of the same order as in cortices of rodents and lagomorphs and much higher than in cortices of advanced terrestrial mammals. Layers I and II contain approximately 70% of the total synapses in the cortical slab through visual cortex. Layer I also contains the extraverted dendrites of neurons of layer II and thus these two layers resemble a paleoarchicortical type of organization superimposed on a more typical neocortical organization of the lower cortical layers. In this respect the convexity neocortex of cetaceans is generally similar to the neocortices of phylogenetically ancient extant mammals such as basal Insectivora and Chiroptera.

Animals