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Biomedical subjects

C Pavlides

Publications and source records attributed to C Pavlides.

At least 19 recordsLinked to original sources
PubMed2001

Half-Fourier acquisition single-shot turbo spin echo imaging in the diagnosis of Morgagni hernia.

Magnetic resonance (MR) imaging with multi-planar, gated Half-Fourier Acquisition Single-Shot Turbo Spin-Echo (HASTE) imaging was performed to evaluate a woman with dysrhythmia. MR examination for right ventricular dysplasia revealed a Morgagni hernia. The HASTE images depicted well the diaphragmatic defect and the organs involved, yielding valuable diagnostic and pre-operative information. HASTE imaging may be beneficial in the evaluation of Morgagni hernia.

Female↗
PubMed2000

Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin(1A) receptors.

The hippocampus is a major limbic target of the brainstem serotonergic neurons that modulate fear, anxiety, and learning through postsynaptic serotonin(1A) receptors (5-HT(1A) receptors). Because chronic stress selectively down-regulates the 5-HT(1A) receptors in the hippocampus, we hypothesized that mice lacking these receptors may exhibit abnormalities reminiscent of symptoms of stress-related psychiatric disorders. In particular, a hippocampal deficit in the 5-HT(1A) receptor could contribute to the cognitive abnormalities often seen in these disorders. To test whether a deficit in 5-HT(1A) receptors impairs hippocampus-related functions, we studied hippocampal-dependent learning and memory, synaptic plasticity in the hippocampus, and limbic neuronal excitability in 5-HT(1A)-knockout (KO) mice. 5-HT(1A)-KO animals showed a deficit in hippocampal-dependent learning and memory tests, such as the hidden platform (spatial) version of the Morris water maze and the delayed version of the Y maze. The performance of KO mice was not impaired in nonhippocampal memory tasks such as the visible platform (nonspatial) version of the Morris water maze, the immediate version of the Y maze, and the spontaneous-alternation test of working memory. Furthermore, paired-pulse facilitation in the dentate gyrus of the hippocampus was impaired in 5-HT(1A)-KO mice. Finally, 5-HT(1A)-KO mice, as compared with wild-type animals, displayed higher limbic excitability manifested as lower seizure threshold and higher lethality in response to kainic acid administration. These results demonstrate that 5-HT(1A) receptors are required for maintaining normal hippocampal functions and implicate a role for the 5-HT(1A) receptor in hippocampal-related symptoms, such as cognitive disturbances, in stress-related disorders.

Animals↗
PubMed2000

Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety.

Anxiety is a common psychiatric illness often treated by benzodiazepines (BZs). BZs, such as Valium, bind to the alpha subunit of the pentameric GABA(A) receptor and increase inhibition in the CNS. There is considerable evidence for abnormal GABA(A) receptor function in anxiety, and a significant proportion of anxiety patients has a reduced sensitivity to BZs. Here, we show that serotonin(1A) (5-HT(1A)) receptor knock-out mice display BZ-resistant anxiety. Consistent with this finding, binding of both BZ and non-BZ GABA(A) receptor ligands were reduced and GABAergic inhibition was impaired in mutant mice. These changes were reflected by abnormal alpha subunit expression in the amygdala and hippocampus, two important limbic regions involved in fear and anxiety. These data suggest a pathological pathway, initiated by a 5-HT(1A) receptor deficit, leading to abnormalities in GABA(A) receptor composition and level, which in turn result in BZ-insensitivity and anxiety. This model mechanistically links together the 5-HT and GABA systems, which both have been implicated in anxiety. A related mechanism may underlie reduced BZ sensitivity in certain forms of anxiety.

Amygdala↗
PubMed2000

Long-term potentiation/depotentiation are accompanied by complex changes in spontaneous unit activity in the hippocampus.

Typically, long-term potentiation (LTP) has been assessed as long-lasting changes in field potentials or intracellularly recorded postsynaptic potentials evoked by activation of a set of afferents. In the present experiment, we determined changes in spontaneous unit activity in the dentate gyrus (DG) following high-frequency (HFS) or low-frequency stimulation (LFS) of the medial perforant pathway. Experiments were performed in anesthetized rats. Field potentials and unit recordings were obtained alternatively from the same recording electrode. Of 39 single units isolated (from 25 independent sessions), the spontaneous discharges of 13 units (33%) increased, while 7 units (18%) decreased their discharges following HFS that induced significant LTP of the field potentials. Such opposing modulations of unit discharges following HFS were observed on simultaneously recorded units. LFS applied following HFS also induced bi-directional effects on unit discharges. Of 20 single units isolated from a subset of recordings (12 experiments) to which LFS was applied, 6 units increased and 4 units decreased their discharges. LFS produced a long-lasting (>20 min) depotentiation, to the baseline level, on field potentials in four recording cases. The autocorrelation functions indicated that the isolated unit discharges were comparable to those of the putative DG granule cells and interneurons, shown in previous studies. The results suggest that changes in synaptic efficacy following HFS or LFS produce rather dynamic changes in cell activity in the DG.

Action Potentials↗
PubMed1999

Effects of mineralocorticoid and glucocorticoid receptors on long-term potentiation in the CA3 hippocampal field.

We have previously shown that the two types of adrenal steroid receptors, mineralocorticoid MR. and glucocorticoid GR. produce opposite effects on long-term potentiation LTP. in the dentate gyrus in vivo. and CA1 hippocampal field in vitro. More specifically, MR activation enhanced and prolonged LTP, whereas GR activation suppressed LTP in these areas and also produced a long-term depression LTD. of the synaptic response. In the present experiment we investigated acute effects of MR and GR activation on LTP induction in the mossy fiber and commissural associational input to the CA3 hippocampal field, since the mechanisms underlying LTP induction in these two pathways differ, the former being N-methyl-D-aspartate receptor NMDAR. independent while the latter being NMDAR-dependent. Rats were either adrenalectomized ADX or adrenally intact. ADX animals were acutely injected with either the specific MR agonist, aldosterone, the specific GR agonist RU 28362 or vehicle. One hour following the injection, the animals were prepared for electrophysiological recording stimulation. Field potential recordings were performed in the radiatum or laconosum moleculare layers of the CA3 field, with stimulation of either the mossy fibers or the commissural associational input from the contralateral hemisphere. We also replicated our previous findings by recording in the dentate gyrus with stimulation of the medial perforant pathway, in the same animals. As observed in our previous study in the dentate gyrus, we found an enhancement and a suppression of LTP with MR and GR activation, respectively. Similarly, for the commissural associational input to CA3, MR activation enhanced LTP, while GR activation reduced it. In contrast, for the mossy fiber input to CA3, neither MR nor GR activation significantly affected LTP induction. These results indicate that adrenal steroids may modulate LTP induction in the hippocampus via an interaction with glutamatergic NMDAR.

Adrenalectomy↗
PubMed1999

11beta-hydroxysteroid dehydrogenase functions reversibly as an oxidoreductase in the rat hippocampus in vivo.

The localization in the brain and metabolism of 3H-labeled corticosterone (B) and 11-dehydrocorticosterone (A) of high specific radioactivity was determined after stereotaxic injection into the hippocampus of anesthetized rats. [3H]B was cleared very rapidly with, on average, only about 7% being recovered after 5 min and 0.5% after 30 min. Most of this 3H-radioactivity was localized in the area surrounding the site of injection with little diffusion to adjacent areas. These findings make it possible to compare the short term metabolism of [3H]A and [3H]B in different lobes of the hippocampus in the same animal and establish their local equilibrium point in vivo. Under these conditions, about 5% conversion of each steroid to the other was observed in contrast to the situation in cultured hippocampal cells where 11beta-hydroxysteroid dehydrogenase (11-HSD) has been shown by others to act primarily as a reductase catalyzing the conversion of A to B. This method can also be used to study the effect of inhibitors such as 11alpha-hydroxyprogesterone, applied locally in the brain, on the metabolism of corticosteroids. The rate of conversion [3H]B or [3H]A to their dihydro- and tetrahydro-derivatives capable of modulating the GABAa receptor in the hippocampus was much lower than their interconversion. Thus, factors which influence the direction of the 11-HSD catalyzed reaction are important in regulating not only salt appetite and blood pressure but also the levels of neuroactive metabolites of corticosterone.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Neurobiological basis of motor learning in mammals.

Long-term potentiation (LTP) has been proposed as a model of learning and memory. There is still little evidence, however, linking LTP to cognitive processes. We have chosen to study motor learning, first, because it is relatively simpler than cognitive learning and second, because much of the circuitry involved in motor function is already known. In behavioral studies we determined that the sensory cortex is required for the acquisition of new motor skills. Once a skill is acquired, however, the sensory cortex is no longer necessary in the performance of that skill. In electrophysiological experiments we have shown that LTP can be induced in the motor cortex with stimulation of the sensory cortex (SCx) or associativly when stimulation was applied to both SCx and thalamus. We propose that motor learning involves the formation of loop circuits between the motor cortex and the periphery involving the SCx and the thalamus. At first these loop circuits are diffuse, producing contraction of unnecessary muscles, but become specific by producing LTP through practice.

Animals↗
PubMed1996

Role of adrenal steroid mineralocorticoid and glucocorticoid receptors in long-term potentiation in the CA1 field of hippocampal slices.

We previously demonstrated in the dentate gyrus (DG) of anesthetized and freely behaving rats that both acute as well as chronic administration of corticosterone produces a suppression in long-term potentiation (LTP). In subsequent studies we showed, again in the DG, that activation of the two types of adrenal steroid receptors (mineralocorticoid (MR) and glucocorticoid (GR)) produce biphasic effects on synaptic plasticity; activation of MR produces an enhancement while activation of GR produces a suppression in LTP. In a separate study, we further demonstrated in rats administered the specific GR agonist RU 28362 that high-frequency stimulation, which normally produces LTP, instead produced long-term depression (LTD) in these animals. In the present study we investigated the effects of MR and GR activation by adrenal steroids on synaptic plasticity of the hippocampal CA1 field, but we studied this ex vivo, in a slice preparation. The results indicate that, as in our studies in the DG, adrenal steroids produce biphasic effects: in ADX rats, aldosterone (a specific MR agonist) enhanced while RU 28362 suppressed synaptic plasticity. Unlike the in vivo preparation, however, rarely was LTD observed in the animals receiving RU 28362. Also, ADX itself did not produce noticeable effects on synaptic plasticity. The present results are in agreement with previous studies showing that elevations in corticosterone or an acute episode of experimentally induced stress in vivo causes a suppression in LTP in the hippocampal CA1 field, in vitro.

Adrenal Glands↗
PubMed1995

Opposing roles of type I and type II adrenal steroid receptors in hippocampal long-term potentiation.

Studies were performed in vivo on the dentate gyrus to investigate the possible involvement of Type I and Type II adrenal steroid receptors in the mediation of reported adrenal steroid effects on long-term potentiation, through the use of specific Type I and Type II receptor agonists and antagonists. In adrenalectomized rats, administration of aldosterone, a specific Type I agonist, produced a marked enhancement in long-term potentiation, in comparison to either the adrenalectomized or sham adrenalectomized controls. Administration of RU 28318, a Type I antagonist, which by itself had minimal effects, blocked the aldosterone enhancement. In contrast, administration of the specific Type II agonist, RU 28362, produced a marked decrement in the induction of long-term potentiation. The RU 28362 effect was blocked by a prior injection of the Type II antagonist, RU 38486. Neither adrenalectomy nor administration of any of the steroid agonists or antagonists had noticeable effects on neuronal excitability (as determined by the field potentials), nor on post-tetanic potentiation. These findings are consistent with other studies that have shown a biphasic effect of increasing levels of corticosterone on long-term or prime burst potentiation. Taken together, these studies suggest that Type I receptors, with a high affinity for corticosterone, and Type II receptors, having a lower affinity for corticosterone, form a two-level recognition system to modulate induced synaptic plasticity in opposite directions in the dentate gyrus and possibly also in Ammon's horn.

Adrenal Cortex Hormones↗
PubMed1995

Hippocampal homosynaptic long-term depression/depotentiation induced by adrenal steroids.

The effects of adrenal steroids on synaptic plasticity were investigated in the dentate gyrus of the hippocampus. Experiments were performed in either adrenalectomized or intact (non-adrenalectomized), anesthetized rats. High-frequency stimulation was applied to the medial perforant pathway at three different frequencies; 100, 200 or 400 Hz, either post- or pre- and post-administration of the specific Type-II adrenal steroid receptor agonist RU 28362. High-frequency stimulation prior to RU 28362 administration produced a frequency-dependent long-term potentiation of the population spike, with 100 Hz showing no long-term potentiation and 400 Hz the highest degree of potentiation. In contrast, following administration of RU 28362, high-frequency stimulation produced a long-term depression (in comparison to baseline). In the experiments in which high-frequency stimulation was applied both pre- and post-RU 28362 administration, the size of the population spike was initially potentiated and then depotentiated after the RU 28362 injection. This effect was also frequency dependent, although opposite to the long-term potentiation effect. That is, 400 Hz was the least effective frequency for inducing long-term depression/depotentiation, while 100 Hz was the most effective. Long-term depression/depotentiation was immediate following high-frequency stimulation and lasted for the extent of the recording session, in some cases longer than 1 h. Similar to the finding reported in the accompanying paper, induction of long-term potentiation was substantially suppressed by RU 28362. However, in a number of experiments long-term potentiation could still be induced after RU 28362 administration, even after long-term depression/depotentiation had been established. In these cases, stimulation at the higher frequencies was necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1994

Type I adrenal steroid receptors prolong hippocampal long-term potentiation.

The effects of Type I adrenal steroid receptors in prolonging synaptic plasticity in the dentate gyrus of freely behaving rats was investigated. Rats were implanted with chronic, bilateral stimulating and recording electrodes in the perforant pathway and dentate gyrus, respectively, and adrenalectomized (ADX). After a 2-3 day recovery period, baseline recordings of field potentials were made followed by administration of aldosterone or vehicle. One hour later, high frequency stimulation (HFS; chosen to produce comparable long-term potentiation (LTP) in the aldosterone-treated and control groups) was applied unilaterally and recording was continued for 1 h and again performed at 3, 24 and 48 h. LTP in ADX controls decayed significantly within 3 h, and returned to baseline levels at 24 h. In contrast, the aldosterone-treated animals showed enhanced LTP at 3, 24 and 48 h. These findings demonstrate that aldosterone both enhances and prolongs hippocampal plasticity.

Adrenal Glands↗
PubMed1993

Effects of glucocorticoids on hippocampal long-term potentiation.

The effects of chronic and acute corticosterone (CORT) administration were investigated on hippocampal long-term potentiation (LTP) in the dentate gyrus granule cell layer of the rat. Electrophysiological experiments were performed in vivo under urethane anesthesia. Chronic CORT treatment (40 mg/kg/day) over 21 days decreased LTP compared to vehicle controls, even when LTP was measured 48 hours after cessation of CORT treatment, when serum CORT levels had returned to baseline. A single injection of CORT also decreased LTP compared to vehicle controls, but only when CORT levels were high, since at 48 hours after a single acute CORT injection LTP was not depressed. The decrements in LTP were seen both for the slope of the excitatory postsynaptic potential and for the population spike. Yet CORT had no effects on posttetanic potentiation or neuronal excitability. These findings are consistent with previous reports showing a reduction in LTP in the CA1 field of animals exposed to stress or acute CORT administration.

Animals↗
PubMed1993

Projection from the sensory to the motor cortex is important in learning motor skills in the monkey.

1. The projection from the somatosensory cortex to the primary motor cortex has been proposed to play an important role in learning novel motor skills. This hypothesis was examined by studying the effects of lesions to the sensory cortex on learning of new motor skills. 2. We used two experimental paradigms to reveal the effects of lesions on learning of new motor skills. One task was to catch a food pellet falling at various velocities. The other task was to catch a food pellet from a rotating level. Both tasks required acquisition of novel motor skills. 3. The training was started after a lesion of the hand area in the somatosensory cortex of one hemisphere. In both tasks, monkeys had severe difficulty in learning the new skills with the hand contralateral to the ablated somatosensory cortex, compared with the hand contralateral to the intact hemisphere. 4. After acquisition of the motor skill in the hand contralateral to intact hemisphere, lesion of the somatosensory cortex hand area did not abolish the learned motor skill. 5. In control experiments, monkeys were trained to pick up a food pellet from a rotating board. This task did not necessitate acquisition of new motor skills, but could be performed by utilizing existing motor skills. Lesion in the somatosensory cortex before or after the training did not affect the execution of this task by either hand. 6. It is concluded that the corticocortical projection from the somatosensory to the motor cortex plays an important role in learning new motor skills, but not in the execution of existing motor skills.

Afferent Pathways↗
PubMed1991

Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning.

Excess thyroid hormone at an early stage of development produces marked neurochemical and morphological alterations in the rat hippocampal formation. In order to better understand the functional significance of these changes, we tested adult rats treated neonatally with triiodothyronine (T3), and their control litter mates, in a spatial learning task and for the induction of long-term potentiation (LTP) in the dentate gyrus (DG) of the hippocampal formation. The T3-treated rats were significantly impaired in their performance on the spatial task in comparison to their matched controls. Similarly, the efficacy of LTP induction was significantly attenuated in the T3-treated animals. Further, a significant correlation was obtained between LTP induction and performance on the spatial learning task. Thus, a brief neonatal excess of thyroid hormone produces impairments in spatial learning along with decreases in LTP, long held as a model of learning and memory. This relationship provides a unique opportunity to study associations between behavioral, physiological, pharmacological and morphological processes intimately associated with the hippocampal formation.

Animals↗
PubMed1991

Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents.

1. Intracellular recordings were obtained from neurons in the motor cortex (MCx), in which excitatory postsynaptic potentials (EPSPs) were evoked by microstimulation of the somatosensory cortex (SCx) and the ventrolateral nucleus (VL) of the thalamus. The effects of combined tetanic stimulation of SCx and VL on the amplitudes of these EPSPs were studied. 2. Amplitudes of both corticocortical (CC) and thalamocortical (TC) EPSPs were potentiated after combined tetanic stimulation. This potentiation occurred exclusively in neurons that were located in the superficial layers (II/III) and that received direct input from both the SCx and VL, with both inputs synapsing in close proximity to each other. In all cases, the potentiation lasted until the electrode went out of the cell (21 +/- 25 min, mean +/- SD) the longest being 90 min. We therefore refer to this potentiation as long-term potentiation (LTP). 3. Tetanic stimulation of the thalamus only did not produce LTP in neurons receiving direct input from the VL. 4. LTP was not induced in either CC or TC EPSPs in neurons located in layer V and/or in neurons receiving long-latency CC EPSPs. 5. It is concluded that TC input from the VL to the MCx is potentiated only when coactivated with the CC input from the SCx.

Animals↗
PubMed1990

On-line acquisition, analysis and presentation of neurophysiological data based on a personal microcomputer system.

A microcomputer based system is described for the acquisition, averaging, displaying, analysis and storage of electrophysiological (EPSP and post-stimulus histogram) data. The system consists of commercially available hardware (IBM-PC AT compatible, 80286 or 80386 based microcomputer, Burr-Brown analog-to-digital (A/D) converter), a custom built interface module, and a combination of commercially available and custom built software packages. The software operates within a Microsoft Windows environment and is comprised of custom built data acquisition and review modules which are linked to Microsoft's Excel program. The system is capable of four channel A/D conversion of EPSP's at a sampling frequency of up to 10 KHz (50 KHz single channel), the averaging of data including the addition and subtraction of various channels, the graphical display of data, the extraction of various data parameters, and the transfer of data to an Excel spreadsheet. The spreadsheet allows for the development of mathematical formulas for statistical analysis of data and presentation of the results in graphical form. Finally, data can easily be output to a laser printer or plotter. A sample experiment, illustrating system operation, is presented.

Electronic Data Processing↗