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At least 775 records · Page 43Linked to original sources
PubMed1993

Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state.

Brain cholinergic neurons are critical for memory function and their loss may contribute to memory impairment in Alzheimer's disease. One role of cholinergic neurons is to elicit an oscillatory activity called theta rhythm in the hippocampus, a brain region involved in memory processing. Theta rhythm occurs during periods of learning, but its effect on the synaptic plasticity that underlies learning remains unclear. We have studied synaptic plasticity in hippocampal slices during theta-frequency oscillations induced by a cholinergic agonist. Here we report that during these oscillations, synapses are in a state of heightened plasticity and can be modified by what would otherwise be ineffective stimulation. This heightened plasticity is sensitive to the timing of incoming stimuli with respect to the oscillatory activity. The results suggest that cholinergic systems may affect memory formation through the induction of an oscillatory state in which the requirements for synaptic plasticity are dramatically altered.

Animals↗
PubMed2005

Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2.

Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2(-/-) mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2(-/-) slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2(-/-) mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2(-/-) mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway.

Animals↗
PubMed2003

Long-term depression induced by sensory deprivation during cortical map plasticity in vivo.

Cortical map plasticity is thought to involve long-term depression (LTD) of cortical synapses, but direct evidence for LTD during plasticity or learning in vivo is lacking. One putative role for LTD is in the reduction of cortical responsiveness to behaviorally irrelevant or unused sensory stimuli, a common feature of map plasticity. Here we show that whisker deprivation, a manipulation that drives map plasticity in rat somatosensory cortex (S1), induces detectable LTD-like depression at intracortical excitatory synapses between cortical layer 4 (L4) and L2/3 pyramidal neurons. This synaptic depression occluded further LTD, enhanced LTP, was column specific, and was driven in part by competition between active and inactive whiskers. The synaptic locus of LTD and these properties suggest that LTD underlies the reduction of cortical responses to deprived whiskers, a major component of S1 map plasticity.

Animals↗
PubMed2006

AMPA receptors regulate transcription of the plasticity-related immediate-early gene Arc.

Learning and memory depend critically on long-term synaptic plasticity, which requires neuronal gene expression. In the prevailing view, AMPA receptors mediate fast excitatory synaptic transmission and effect short-term plasticity, but they do not directly regulate neuronal gene expression. By studying regulation of Arc, a gene required for long-term plasticity, we uncovered a new role for AMPA receptors in neuronal gene expression. Spontaneous synaptic activity or activity induced by brain-derived neurotrophic factor (BDNF) elicited Arc expression in cultures of rat cortical neurons and in organotypic brain slices. Notably, inhibiting AMPA receptors strongly potentiated activity-dependent Arc expression. We found that AMPA receptors negatively regulate Arc transcription, but not translation or stability, through a mechanism involving a pertussis toxin-sensitive G protein. These results provide insights into the activity-dependent mechanisms of Arc expression and suggest that, in addition to effecting short-term plasticity, AMPA receptors regulate genes involved in long-term plasticity.

Animals↗
PubMed2005

The autofluorescence of plastic materials and chips measured under laser irradiation.

Plastic materials have the potential to substitute for glass substrates used in microfluidic and microTAS systems adding flexibility in materials' choices. Optical quality plastic materials with a low autofluorescence are crucial for optimal detection by fluorescence and laser induced fluorescence techniques. This paper summarizes a series of optical investigations on commercially available plastic chip materials (PMMA, COC, PC, PDMS) and chips made from those materials. Intrinsic optical constants of plastic materials-refractive index for bulk materials-determined by spectroscopic ellipsometry and transmission spectroscopy in the visible range are presented. The laser-induced autofluorescence of materials and chips was assessed at four laser wavelengths, namely, 403, 488, 532 and 633 nm. Considerable bleaching of the autofluorescence was observed under continuous laser illumination. Overall, the longer wavelength laser excitation sources yielded less autofluorescence. PDMS exhibited the least autofluorescence and was comparable to BoroFloat glass. In all cases, chips exhibited slightly higher autofluorescence than the raw plastic materials from which they had been made.

Equipment Failure Analysis↗
PubMed1999

Syk and paxillin are differentially phosphorylated following adhesion to the plastic substrate in rat alveolar macrophages.

Adhesion is associated with tyrosine phosphorylation in many types of cells. Although macrophages are known to adhere and phagocytose foreign particles, the signal transduction pathway of macrophages in response to adhesion to the foreign substrate has not been fully investigated. In the present study we investigated tyrosine-phosphorylated proteins and phosphorylation of paxillin in alveolar macrophages (AMs) following adhesion to a plastic substrate. Adhesion to a plastic dish resulted in tyrosine phosphorylation of a 68 000 MW protein, which was shown, by immunoprecipitation and immunoblotting in the present study, to be a rat Syk kinase. Treatment with erbstatin reduced both tyrosine phosphorylation of Syk and adherence of AMs, while treatment with cytochalasin B inhibited spreading of AMs but did not inhibit tyrosine phosphorylation of Syk. These results suggest that tyrosine phosphorylation of Syk plays an important role in adhesion of AMs to the plastic substrate, but not in AM spreading. Paxillin is known to be tyrosine phosphorylated following adhesion to the extracellular matrix in many types of cells. However, paxillin appeared to be serine/threonine phosphorylated rather than tyrosine phosphorylated following adhesion of AMs to the plastic substrate. Treatment with A23187 (a calcium ionophore), but not phorbol 12-myristate 13-acetate (PMA; a protein kinase C stimulator), induced tyrosine phosphorylation of Syk in non-adherent AMs. Treatment with either A23187 or PMA caused electromobility changes of paxillin that were mainly a result of serine/threonine phosphorylation. These results suggest that adhesion to the plastic substrate leads to two differently regulated events in AMs: tyrosine phosphorylation of Syk and serine/threonine phosphorylation of paxillin, both of which are probably mediated by an increase in intracellular calcium.

Animals↗
PubMed2003

Comparative retrospective study on the use of plastic prostheses and self-expanding metal stents in the palliative treatment of malignant strictures of the esophagus and cardia.

Palliative treatment of malignant strictures of the esophagus and cardia is usually carried out by the endoscopic placement of a prosthesis. The aim of this retrospective study was to evaluate short- and long-term outcomes of the use of expandable stents, compared with conventional plastic prostheses. One hundred and thirteen endoscopic intubations were carried out in 120 patients affected by malignant stenosis of the esophagus and cardia using plastic prosthesis and self-expanding metal stents. Dysphagia was scored according to Atkinson and Ferguson's classification and the preoperative median score (3.6) was comparable in both groups. The technical success rate was 94.4% with plastic prosthesis and 93.7% with self-expanding metal stent while the functional success rate was, respectively, 85.2% and 88.8%. Three deaths occurred with plastic prostheses (4.4%), while no deaths were observed with metal stents. A comparative analysis of the results of this study suggests that the endoscopic placement of self-expanding metal stents is effective and safe and has to be preferred to the conventional plastic prosthesis for easier implantation and lower morbidity.

Adenocarcinoma↗
PubMed2000

The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord.

Activity-dependent synaptic plasticity has been proposed as a contributory factor in the patterning of rhythmic network activity. However, its role has not been examined in detail. Here, paired or triple intracellular recordings have been made from identified neurons in the lamprey locomotor network to examine the potential relevance of activity-dependent synaptic plasticity in segmental and intersegmental spinal networks. Segmental inputs from glutamatergic excitatory interneurons (EIN) to ipsilateral glycinergic crossed caudal (CC) interneurons were facilitated or depressed during spike trains at 5-20 Hz. Connections between EINs were depressed. Glycinergic inputs from small ipsilateral inhibitory interneurons were depressed in motor neurons, but were facilitated in CC interneurons. Excitatory inputs from small crossing interneurons to motor neurons were depressed, whereas inhibitory inputs were unaffected. With the exception of connections between EINs, significant effects occurred with stimulation that mimicked interneuron spiking during network activity. Intersegmental EIN synaptic properties were also investigated. EIN inputs did not differ significantly when examined from zero to four segments rostral to motor neurons or CC interneurons. However, caudally located EINs evoked greater activity-dependent facilitation than did rostral EINs. Whilst the amplitude or plasticity of EIN inputs in the rostral or mid-trunk regions of the spinal cord did not differ, EINs in the caudal trunk region evoked greater facilitation. Synaptic transmission between locomotor network neurons thus exhibits activity-dependent plasticity in response to physiologically relevant stimulation. Activity-dependent plasticity could thus contribute to the patterning of the rhythmic network output.

Action Potentials↗
PubMed1994

Characteristics of white cell-reduced red cells stored in tri-(2-ethylhexyl)trimellitate plastic.

BACKGROUND: Standard blood storage containers contain extractable plasticizers that accumulate in blood during storage and are an unintended transfusion product. However, extractable plasticizers have a protective effect on the red cell membrane and improve red cell storage variables. Prestorage white cell reduction also improves selected red cell storage variables. STUDY DESIGN AND METHODS: The study evaluated whether the beneficial effect of prestorage white cell reduction would offset the negative effect of the absence of extractable plasticizer in red cells stored in AS-3 for 42 days at 4 degrees C. Filtered red cells stored in polyvinylchloride containers with the nonextracting plasticizer, tri-(2-ethylhexyl)trimellitate (TEHTM), were compared to unfiltered red cells stored in polyvinylchloride containers with the extractable plasticizer di-(2-ethylhexyl)phthalate (DEHP). RESULTS: Poststorage supernatant potassium and red cell osmotic fragility were significantly higher in white cell-reduced TEHTM units than in unfiltered DEHP units. The mean 24-hour recovery of the filtered TEHTM red cells was significantly lower than that of the unfiltered DEHP red cells (69.1 +/- 7.4% vs. 77.1 +/- 5.1%, p < 0.05, n = 8). CONCLUSION: These data demonstrate that white cell reduction before 42-day storage in TEHTM containers with currently approved preservatives does not yield an acceptable red cell component.

Adenosine Triphosphate↗
PubMed2004

Amphetamine enhances training-induced motor cortex plasticity.

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.

Adult↗
PubMed2005

[Synaptic plasticity and neuropathology: new approaches in drug discovery].

Neuronal plasticity is now known to be very important in the adult, both in the formation of new synaptic connections and of new neurones (neurogenesis) and of glial cells. However, old age and stress can inhibit this plasticity and lead to cerebral atrophy. The time course of changes in neuronal plasticity involves, in the first milliseconds to seconds, changes in synaptic strength (long term potentialisation, LTP, or long term depression, LTD), then, over minutes to hours, changes in the number of synaptic connections (linked to changes in neurotrophic factors), and over weeks to months, to changes in neuronal reconfiguration. These changes in brain systems are particularly targeted in psychiatric disorders to the areas which are sensitive to stress and play roles in memory and emotion (hippocampus, amygdala and prefrontal cortex). The discovery and development of drugs modifying neuronal plasticity and neurotrophins production has been a priority for Servier research for the last ten years; Servier has a clinically effective antidepressant, tianeptine (Stablon), with a favourable side effect profile, but which does not inhibit the uptake of serotonin, or other monoamines. However, this drug can reverse the deleterious effects of stress on neuronal plasticity, thereby acting on the causes of psychiatric disorders. Furthermore, a new research area is being investigated - facilitation of AMPA receptors, favouring the production of neurotrophic factors.

Animals↗
PubMed2002

The influence of plasticizer loss on the viscoelasticity of temporary soft liners.

PURPOSE: This study examined the changes in mechanical properties of temporary soft liners introduced by the differential loss of alcohol and plasticizer in different storage media. MATERIALS AND METHODS: Four brands of temporary soft liners were used to prepare 128 specimens on Lucite LS substrates. Each group of specimens was stored in a different medium (air, 10% ethanol, water, and artificial saliva), selected to affect the levels of plasticizer and alcohol over time. Data on weight changes, plasticizer leaching, and recovery rate were recorded at the following intervals: baseline, 2, 7, 14, 28, 56, and 176 days. The storage media were periodically renewed except during the drying stage between day 56 and 176. Two-way analysis of variance and Duncan multiple-range tests were performed. RESULTS: Plasticizer leaching occurs at higher levels in artificial saliva than in other storage media (P <.0001). The mean recovery rates exhibited a statistically significant increase (indicating reduced viscoelasticity) in more of the artificial saliva specimens than in all other test groups (P <.0001). Comparatively, the rates of recovery were lower in the 10% ethanol storage medium (except Lynal) with a statistically significant difference attained with the higher air-stored specimens in Tempo and Coe-Comfort (P <.0001). During the drying phase, weight changes in the 10% ethanol group were higher than those in the other storage media. CONCLUSIONS: The study supports the contention that alcohol may have been retained in the 10% ethanol group in a manner that extended the viscoelasticity of the material. The roles of alcohol and plasticizer content in the mechanical properties of temporary soft liners depend on the type of temporary soft liners and on the nature/duration of service desired. Storing dentures lined with tissue conditioners under dry conditions and those lined with true soft-liners in an ethanol humidor may be justified to extend serviceability by minimizing the loss of the component most relevant to viscoelasticity.

Air↗
PubMed2000

Assessing adolescents and young girls for plastic surgical intervention: pre-surgical appearance ratings and appearance-related burdens as reported by adolescents and young adults, parents and surgeons.

Currently available research on psychological aspects of plastic surgery offers little basis for clinical decision making in the plastic surgeon's assessment of adolescents and young adults applying for surgery. Therefore, the research aims were to study: first, how these adolescents and young adults estimate their appearance as compared to their parents and plastic surgeons to determine the reality of their own appearance perception; second, what appearance-related burdens they experience to determine the urgency of their request for surgery; and third, the surgeons' considerations for the operation. Data were obtained from 184 plastic surgical patients aged 12-22 years (71.2% girls), 172 of their parents and 37 surgeons from 16 hospitals in The Netherlands, using appearance rating scales and to surgeons and parents, and reported substantial appearance-related suffering. There was a moderate to large overlap between the adolescent- and parent-reported burdens. In their assessment, surgeons took psychological and social impediments into consideration. In conclusion, plastic surgeons may rightfully assume that adolescents and young adults have a realistic view of their appearance and that they suffer from significant appearance-related burdens. Parents prove to be an important additional source of information.

Adolescent↗
PubMed2001

Theory for normal and impaired experience-dependent plasticity in neocortex of adult rats.

We model experience-dependent plasticity in the cortical representation of whiskers (the barrel cortex) in normal adult rats, and in adult rats that were prenatally exposed to alcohol. Prenatal exposure to alcohol (PAE) caused marked deficits in experience-dependent plasticity in a cortical barrel-column. Cortical plasticity was induced by trimming all whiskers on one side of the face except two. This manipulation produces high activity from the intact whiskers that contrasts with low activity from the cut whiskers while avoiding any nerve damage. By a computational model, we show that the evolution of neuronal responses in a single barrel-column after this sensory bias is consistent with the synaptic modifications that follow the rules of the Bienenstock, Cooper, and Munro (BCM) theory. The BCM theory postulates that a neuron possesses a moving synaptic modification threshold, theta(M), that dictates whether the neuron's activity at any given instant will lead to strengthening or weakening of its input synapses. The current value of theta(M) changes proportionally to the square of the neuron's activity averaged over some recent past. In the model of alcohol impaired cortex, the effective theta(M) has been set to a level unattainable by the depressed levels of cortical activity leading to "impaired" synaptic plasticity that is consistent with experimental findings. Based on experimental and computational results, we discuss how elevated theta(M) may be related to (i) reduced levels of neurotransmitters modulating plasticity, (ii) abnormally low expression of N-methyl-d-aspartate receptors (NMDARs), and (iii) the membrane translocation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in adult rat cortex subjected to prenatal alcohol exposure.

Action Potentials↗
PubMed2002

Permissive proteolytic activity for visual cortical plasticity.

The serine protease, tissue-type plasminogen activator (tPA) is a key regulator of extracellular proteolytic cascades. We demonstrate a requirement for tPA signaling in the experience-dependent plasticity of mouse visual cortex during the developmental critical period. Proteolytic activity by tPA in the binocular zone was typically increased within 2 days of monocular deprivation (MD). This regulation failed to occur in glutamic acid decarboxylase (GAD) 65 knockout mice, an animal model of impaired ocular dominance plasticity because of reduced gamma-aminobutyric acid (GABA)-mediated transmission described previously. Loss of responsiveness to the deprived eye consequent to MD was conversely suppressed in mice lacking tPA despite normal levels of neuronal activity. Plasticity was restored in a gene dose-dependent manner, or by direct tPA infusion. Permissive amounts of tPA may, thus, couple functional to structural changes downstream of the excitatory-inhibitory balance that triggers visual cortical plasticity. Our results not only support a molecular cascade leading to neurite outgrowth after sensory deprivation, but also identify a valuable tool for further proteomic and genomic dissection of experience-dependent plasticity downstream of electrical activity.

Animals↗
PubMed2002

Dynamical model of long-term synaptic plasticity.

Long-term synaptic plasticity leading to enhancement in synaptic efficacy (long-term potentiation, LTP) or decrease in synaptic efficacy (long-term depression, LTD) is widely regarded as underlying learning and memory in nervous systems. LTP and LTD at excitatory neuronal synapses are observed to be induced by precise timing of pre- and postsynaptic events. Modification of synaptic transmission in long-term plasticity is a complex process involving many pathways; for example, it is also known that both forms of synaptic plasticity can be induced by various time courses of Ca(2+) introduction into the postsynaptic cell. We present a phenomenological description of a two-component process for synaptic plasticity. Our dynamical model reproduces the spike time-dependent plasticity of excitatory synapses as a function of relative timing between pre- and postsynaptic events, as observed in recent experiments. The model accounts for LTP and LTD when the postsynaptic cell is voltage clamped and depolarized (LTP) or hyperpolarized (LTD) and no postsynaptic action potentials are evoked. We are also able to connect our model with the Bienenstock, Cooper, and Munro rule. We give model predictions for changes in synaptic strength when periodic spike trains of varying frequency and Poisson distributed spike trains with varying average frequency are presented pre- and postsynaptically. When the frequency of spike presentation exceeds approximately 30-40 Hz, only LTP is induced.

Long-Term Potentiation↗
PubMed2002

Quality and safety aspects of reusable plastic food packaging materials: influence of reuse on intrinsic properties.

The aim of the project was to develop a comprehensive package of quality assurance criteria for use by the industry and by regulatory authorities to ensure the quality and safety-in-use (sensory, microbiological and chemical safety) of reused plastics for food packaging. The paper describes the investigations into potential adulteration effects by reuse on the intrinsic properties of plastics in more detail. The plastic articles investigated were bottles of polyethylene terephthalate (PET) or polycarbonate (PC) and vending cups of polypropylene (PP). The influence of repeated use on the migration of plastic constituents, degradation products of plastic additives, barrier properties and surface characteristics were investigated. The overall conclusion was that the investigated intrinsic properties of the refillable articles were not significantly influenced by repeated use. Only the hydrophobicity of the refillable PC and PP articles seemed to be influenced by repeated washing. PC bottles washed 15 times were significantly less hydrophobic than unwashed bottles.

Consumer Product Safety↗
PubMed2005

Non-targeted multi-component analytical surveillance of plastic food contact materials: Identification of substances not included in EU positive lists and their risk assessment.

A procedure used by the Norwegian Food Safety Authority for surveillance of contaminants from plastic food contact materials (polyolefin drinking bottles, water boilers, polyamide cooking utensils and plastic multi-layer materials) is described. It is based on gas chromatographic-mass spectrometric (GC/MS) analysis of food simulants exposed to plastic materials. Most migrants were substances not-intentionally added to the plastic (degradation products, impurities) or originated from non-plastic components, such as printing inks, adhesives, not-listed additives, solvents and coatings. Hence, the majority of the identified migrants were regulated by the general statements in the EU Framework Regulation, which neither specify limits nor requirements regarding risk assessment, rather than by specific migration controls. Risk assessment has been carried out for selected non-authorized substances. The analysis and the management of these substances and materials with respect to safety represents a challenge to the food authorities.

Aniline Compounds↗