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Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function.

Insufficient sleep impairs cognitive functions in humans and animals. However, whether long-term synaptic plasticity, a cellular substrate of learning and memory, is compromised by sleep loss per se remains unclear because of confounding factors related to sleep deprivation (SD) procedures in rodents. Using an ex vivo approach in C57BL/6J mice, we show that sleep loss rapidly and reversibly alters bidirectional synaptic plasticity in the CA1 area of the hippocampus. A brief (approximately 4 h) total SD, respecting the temporal parameters of sleep regulation and maintaining unaltered low corticosterone levels, shifted the modification threshold for long-term depression/long-term potentiation (LTP) along the stimulation frequency axis (1-100 Hz) toward the right. Reducing exposure to sensory stimuli by whisker trimming did not affect the SD-induced changes in synaptic plasticity. Recovery sleep reversed the effects induced by SD. When SD was combined with moderate stress, LTP induction was not only impaired but also occluded. Both electrophysiological analysis and immunoblotting of purified synaptosomes revealed that an alteration in the molecular composition of synaptically activated NMDA receptors toward a greater NR2A/NR2B ratio accompanied the effects of SD. This change was reversed after recovery sleep. By using an unparalleled, particularly mild form of SD, this study describes a novel approach toward dissociating the consequences of insufficient sleep on synaptic plasticity from nonspecific effects accompanying SD in rodents. We establish a framework for cellular models of cognitive impairment related to sleep loss, a major problem in modern society.

Animals↗

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

Animals↗

The role of extracellular adenosine in regulating mossy fiber synaptic plasticity.

Hippocampal mossy fiber synapses show unique molecular features and dynamic range of plasticity. A recent paper proposed that the defining features of mossy fiber synaptic plasticity are caused by a local buildup of extracellular adenosine (Moore et al., 2003). In this study, we reassessed the role of ambient adenosine in regulating mossy fiber synaptic plasticity in mouse and rat hippocampal slices. Synaptic transmission was highly sensitive to activation of presynaptic adenosine A1 receptors (A1Rs), which reduced transmitter release by >75%. However, most of A1Rs were not activated by ambient adenosine. Field potentials increased only by 20-30% when A1Rs were fully blocked with the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (1 microM). Moreover, blocking A1Rs hardly altered paired-pulse facilitation, frequency facilitation, or posttetanic potentiation. Frequency facilitation was similar in A1R-/- mice and when measured with NMDA receptor-mediated EPSCs in CA3 pyramidal cells in the presence of DPCPX. Additional experiments suggested that the results obtained by Moore et al. (2003) can partially be explained by their usage of a submerged recording chamber and elevated divalent cation concentrations. In conclusion, a reduction of the basal release probability by ambient adenosine does not underlie presynaptic forms of plasticity at mossy fiber synapses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Fornix lesions decouple the induction of hippocampal arc transcription from behavior but not plasticity.

The immediate-early gene (IEG) Arc is transcribed after behavioral and physiological treatments that induce synaptic plasticity and is implicated in memory consolidation. The relative contributions of neuronal activity and learning-related plasticity to the behavioral induction of Arc remain to be defined. To differentiate the contributions of each, we assessed the induction of Arc transcription in rats with fornix lesions that impair hippocampal learning yet leave cortical connectivity and neuronal firing essentially intact. Arc expression was assessed after exploration of novel environments and performance of a novel water maze task during which normal rats learned the spatial location of an escape platform. During the same task, rats with fornix lesions learned to approach a visible platform but did not learn its spatial location. Rats with fornix lesions had normal baseline levels of hippocampal Arc mRNA, but unlike normal rats, expression was not increased in response to water maze training. The integrity of signaling pathways controlling Arc expression was demonstrated by stimulation of the medial perforant path, which induced normal synaptic potentiation and Arc in rats with fornix lesions. Together, the results demonstrate that Arc induction can be decoupled from behavior and is more likely to indicate the engagement of synaptic plasticity mechanisms than synaptic or neuronal activity per se. The results further imply that fornix lesions may impair memory in part by decoupling neuronal activity from signaling pathways required for long-lasting hippocampal synaptic plasticity.

Animals↗

Malleability of spike-timing-dependent plasticity at the CA3-CA1 synapse.

The magnitude and direction of synaptic plasticity can be determined by the precise timing of presynaptic and postsynaptic action potentials on a millisecond timescale. In vivo, however, neural activity has structure on longer timescales. Here we show that plasticity at the CA3-CA1 synapse depends strongly on parameters other than millisecond spike timing. As a result, the notion that a single spike-timing-dependent plasticity (STDP) rule alone can fully describe the mapping between neural activity and synapse strength is invalid. We have begun to explore the influence of additional behaviorally relevant activity parameters on STDP and found conditions under which underlying spike-timing-dependent rules for potentiation and depression can be separated from one another. Potentiation requires postsynaptic burst firing at 5 Hz or higher, a firing pattern that occurs during the theta rhythm. Potentiation is measurable after only tens of presynaptic-before-postsynaptic pairings. Depression requires hundreds of pairings but has less stringent long timescale requirements and broad timing dependence. By varying these parameters, we obtain STDP curves that are long-term potentiation only, bidirectional, or long-term depression only. This expanded description of the CA3-CA1 learning rule reconciles apparent contradictions between spike-timing-dependent plasticity and previous work at CA3-CA1 synapses.

Animals↗

Plastic cup traps equipped with light-emitting diodes for monitoring adult Bemisia tabaci (Homoptera: Aleyrodidae).

Equipping the standard plastic cup trap, also known as the CC trap, with lime-green light-emitting diodes (LED-plastic cup trap) increased its efficacy for catching Bemisia tabaci by 100%. Few Eretmocerus eremicus Rose and Zolnerowich and Encarsia formosa Gahan were caught in LED-plastic cup traps. The LED-plastic cup traps are less expensive than yellow sticky card traps for monitoring adult whiteflies in greenhouse crop production systems and are more compatible with whitefly parasitoids releases for Bemisia nymph control.

Animals↗

Effects of UV-absorbing plastic films on greenhouse whitefly (Homoptera: Aleyrodidae).

Studies were conducted to investigate the effects of ultraviolet (UV)-absorbing plastic films on the orientation and distribution behavior of the greenhouse whitefly, Trialeurodes vaporariorum (Westwood). In field experiments, small tunnels were constructed and covered with either an UV-transmitting (Thermilux) or UV-absorbing (K-Rose) plastic film. Results show that significantly more whiteflies were recorded in the tunnels with high compared with those with low UV intensities. Moreover, whitefly penetration and dispersion were less inside the UV-deficient tunnels. These results suggest that the type of plastic film used for greenhouse covers may have a significant influence on both the initial immigration and distribution of T. vaporariorum into greenhouses. The possibilities of using UV-absorbing plastic films for whitefly integrated pest management in greenhouses are discussed.

Agriculture↗

The effects of scaling a titanium implant surface with metal and plastic instruments: an in vitro study.

The surface roughnesses of pure titanium implants were compared with scaling in vitro with curettes of dissimilar composition. Each of 10 transmucosal implant extensions (TIEs) was divided into three experimental surfaces and an untreated control surface. The three experimental surfaces were instrumented with either a titanium-alloy tipped curette, a curette of stainless steel, or a plastic curette. All experimental surfaces received 30 strokes with the designated curette within a 2 mm wide area. Alteration of the surfaces due to instrumentation was evaluated by a helium neon (HeNe) laser and reported as relative specular reflectance (RSR). Scanning electron microscopy (SEM) conformed the quantitative HeNe laser results. A significant decrease in mean RSR (greater roughness) was observed for surfaces treated by metal curettes compared to either untreated control surfaces (P less than 0.01) or surfaces treated by the plastic curette (P less than 0.01). No statistically significant difference was noted between untreated surfaces and those treated by the plastic curette. The titanium-alloy curette produced a significantly lower mean RSR (greater roughness) compared to those surfaces treated by the stainless steel curette (P less than 0.05). In summary, plastic instruments produced an insignificant alteration of the titanium implant surface following instrumentation, while metal instruments significantly altered the titanium surface.

Alloys↗

Neuronal plasticity, stress and depression: involvement of the cytoskeletal microtubular system?

In susceptible individuals, stressors can increase the risk of onset of depression and recent brain imaging studies have shown morphometric alterations in the limbic system of patients affected by depression. The volume loss observed in the hippocampus of depressed individuals suggests a possible involvement of structural neuronal plasticity in the pathogenesis of depression. Stressful conditions in animals can result in impaired structural neuronal plasticity in the hippocampus, characterised by retraction of apical dendrites and decreased neurogenesis. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal remodelling and plasticity. We have recently shown that both acute and chronic stress decrease microtubular dynamics in the rat hippocampus. Other authors have demonstrated that proteins functionally involved in the regulation of microtubule dynamics can be altered by stress in the rodent hippocampus. Furthermore, the existence of a link between stress-induced microtubular changes and depression is further strengthened by evidence showing that both acute and chronic treatment with antidepressant drugs can affect the expression of microtubular proteins. The present review will introduce a growing body of evidence suggesting that stress-induced alterations in neuronal plasticity might be considered the final result of activation and/or inhibition of molecular cascades regulating the dynamics of the microtubular system. In addition, the prospect of targeting microtubules as a pharmacotherapeutic approach to treat mood disorders will be discussed.

Animals↗

Brain plasticity in health and disease.

Research during the last decades has greatly increased our understanding of brain plasticity, i.e. how neuronal circuits can be modified by experience, learning and in response to brain lesions. Currently available neuroimaging techniques that make it possible to study the function of the human brain in vivo have had an important impact. Cross-modal plasticity during development is demonstrated by cortical reorganization in blind or deaf children. Early musical training has lasting effects in shaping the brain. Albeit the plasticity is largest during childhood, the adult brain retains a capacity for functional and structural reorganization that earlier has been underestimated. Recent research on Huntington's disease has revealed the possibility of environmental interaction even with dominant genes. Scientifically based training methods are now being applied in rehabilitation of patients after stroke and trauma, and in the sensory retraining techniques currently applied in the treatment of focal hand dystonia as well as in sensory re-education after nerve repair in hand surgery. There is evidence that frequent participation in challenging and stimulating activities is associated with reduced cognitive decline during aging. The current concept of brain plasticity has wide implication for areas outside neuroscience and for all human life.

Brain↗

Target-specific regulation of synaptic efficacy in the feeding central pattern generator of Aplysia: potential substrates for behavioral plasticity?

The contributions to this symposium are unified by their focus on the role of synaptic plasticity in sensorimotor learning. Synaptic plasticities are also known to operate within the central pattern generator (CPG) circuits that produce repetitive motor programs, where their relation to adaptive behavior is less well understood. This study examined divergent synaptic plasticity in the signaling of an influential interneuron, B20, located within the CPG that controls consummatory feeding-related behaviors in Aplysia. Previously, B20 was shown to contain markers for catecholamines and GABA (Díaz-Ríos et al., 2002), and its rapid synaptic signaling to two follower motor neurons, B16 and B8, was found to be mediated by dopamine (Díaz-Ríos and Miller, 2005). In this investigation, two incremental forms of increased synaptic efficacy, facilitation and summation, were both greater in the signaling from B20 to B8 than in the signaling from B20 to B16. Manipulation of the membrane potentials of the two postsynaptic motor neurons did not affect facilitation of excitatory postsynaptic potentials (EPSPs) to either follower cell. Striking levels of summation in B8, however, were eliminated at hyperpolarized membrane potentials and could be attributed to distinctive membrane properties of this postsynaptic cell. GABA and the GABAB agonist baclofen increased facilitation and summation of EPSPs from B20 to B8, but not to B16. The enhanced facilitation was not affected when the membrane potential of B8 was pre-set to hyperpolarized levels, but GABAergic effects on summation were eliminated by this manipulation. These observations demonstrate a target-specific amplification of synaptic efficacy that can contribute to channeling the flow of divergent information from an intrinsic interneuron within the buccal CPG. They further suggest that GABA, acting as a cotransmitter in B20, could induce coordinated and target-specific pre- and postsynaptic modulation of these signals. Finally, we speculate that target-specific plasticity and its modulation could be efficient, specific, and flexible substrates for learning-related modifications of CPG function.

Animals↗

Interaction between plastic catheter tubings and regular insulin preparations used for continuous subcutaneous insulin-infusion therapy.

In search of possible interactions between plastic tubings used for insulin-pump treatment and commercial regular insulin preparations, various catheter sets made from polyvinyl chloride (PVC), polyethylene (PE), and nylon plastics were perfused at 30 degrees C in a laboratory setting for up to 72 h. The perfused insulin solutions were analyzed by high-performance liquid chromatography and atomic absorption spectroscopy. Although no plasticizer, e.g., dioctyl phthalate, or nickel or chromium ions were found in the perfusates, substantial interactions between the plastics and the insulin solutions were detected, extraction of bacteriostatic additives from the insulin solutions in particular. The PVC retained up to 88% of the bacteriostatics from the insulin preparations, whereas PE tubings retained only 10-15%. Whether the loss of preservatives during perfusion through PVC catheters predisposes to cutaneous infections during insulin-pump therapy remains to be shown.

Catheterization↗

Inert plastics as indicators of physiological processes in the gastrointestinal tract of ruminants.

Various types of plastics with different physical properties have been useful in measuring rumination and passage events in the gastrointestinal tract (GIT) of ruminants. Plastic ribbons and monofilaments are available in different diameters, specific gravities and hardness and they can be cut to various lengths. Specific studies that are amenable to these materials include physical appetite control, regurgitation for rumination, passage from the rumen with or without rumination and passage through the entire GIT. Passage of particles through specific portions of the GIT can be measured in animals with various fistula preparations. The rumination of plastic ribbon in the rumen is similar to that of long forage. If the particle length is 7 cm or less, the particle can be regurgitated and produces normal rumination patterns. Movement of particles from one part of the rumen to another can be measured. Multiple sites can be studied in the same experiment by using particles of different colors. Isolating particles from ingesta or fecal residues usually starts with sieving to remove the small particles. Various subsequent separation schemes include flotation or sedimentation, air streams or acid digestion; when other methods fail, particles can be manually separated and counted. Plastic markers have several potential uses in ruminant research but they also have limitations. Because they are inert, they cannot undergo the hydration, density and size changes that occur with normal feed particles.

Animals↗

Nephrotoxicity of plasticizers investigated by 48 hours hypothermic perfusion of dog kidneys.

The possible nephrotoxicity of the plasticizers diethyl phthalate and di-2-ethylhexyl phthalate was tested in vitro using a 48 hours continuous pulsatile hypothermic perfusion of canine kidneys with a human albumin perfusion medium. Since polysorbate 80 was used to facilitate the solution of the plasticizers in the perfusion medium, this substance was also tested. Six groups containing 9--15 kidneys were perfused with different amounts of plasticizers and/or polysorbate 80 added. In perfusates containing polysorbate 80 either alone or with one of the two plasticizers, the LDH activity and the potassium concentrations rose significantly higher than in the control group (p less than 0.001). The kidney weight gain was also significantly greater in these groups. A "blind" histological examination of needle biopsies by light microscopy revealed no differences among the groups. Although the biochemical evidence of tissue damage was not tested by re-implantation of the kidneys, we suggest that caution should be exercised in the use of polysorbate 80 in organ perfusion systems.

Animals↗

Plasticity in the adult and neonatal central nervous system.

The adult nervous system is capable of plastic change; studies have shown that plasticity is part of normal adaptation to daily life as well as being part of the response to trauma. The structural substrates of plastic change are described, and the hypotheses for explaining functional recovery in adults following trauma are reviewed. Events in normal brain development are summarized, and experiments designed to investigate the processes involved are described. The brain of the neonate is a much more plastic structure than that of the adult, both in normal development and in response to trauma. Activity in pathways is an essential component for consolidation of connections, whether normal or compensatory. Experiments which elucidate the mechanisms of axonal/target recognition are described. Recent work on the possible development of therapeutic agents to enhance recovery from trauma, in both adults and neonates, is reviewed. An attempt is made to link the findings from basic research to the clinical field.

Adult↗

Tannic acid-iron alum reactions: stain of choice for macroscopic sections of brain to be embedded in plastic.

As a macroscopic stain for gross brain sections to be embedded in plastic, tannic acid-iron alum is superior to the generally recommended LeMasurier's variation of the Berlin blue technique because of its greater permanency in plastic. However, as originally adopted for use with brain tissue by Mulligan, the intense black staining of gray matter is too dark for plastic embedded specimens. A modification of this method designed to overcome this difficulty is described. Staining procedure: Wash formalin-fixed brain slices overnight in running water. Wash in distilled water, 2 changes, 30 minutes each. Place slices individually in Mulligan's solution at a temperature of 60-65 C for 4 minutes. Rinse in ice water for 10 seconds. Mordant in 0.4% tannic acid in distilled water for 1 minute. Wash in running tap water for 1 minute. Develop in 0.08% ferric ammonium sulfate in distilled water until gray matter is light gray, about 10-15 seconds. Wash in lukewarm running water for 1 hour, then gently hand-rub whitish film from myelinated surfaces. Store briefly in 3% formalin or 25% glycerine if necessary depending on plastic embedding procedure to be followed.

Aluminum↗

Safety evaluation of medical plastics.

At present, there is no evidence of toxicity from the use of PVC plasticized plastics in medical practice. The major components of plasticized PVC have been examined over a span of years and each passing year sees a confirmation of the lack of toxicity. From time to time, misconceptions of new workers in the field may raise issues that have been examined and found to no longer be issues. Considering all the factors of cost, convenience, and safety, it appears that plasticized PVC containers continue to have a valuable place in medical practice.

Animals↗

Relationship between plasticizer content and tensile bond strength of soft denture liners to a denture base resin.

The purpose of this study was to determine the influence of plasticizer content on the tensile bond strength of heat-cured acrylic soft denture liners to a denture base resin. Differences among materials were significant, except for 100 wt% Dibutyl Sebacate (DBS) and 80 wt% DBS of tensile bond strength. The bond strength of all materials to the denture base increased with an increase in thermal cycles significantly except for 40 wt% DBS. The tensile bond strength of soft denture liners to the denture base resin significantly decreased with an increase of plasticizer contents. Differences were found among the difference plasticizer contents in failure types between the denture base resin and soft denture liners. The results suggest that the tensile bond strengths of heat-cured acrylic soft denture liners to the denture base resin were lower with an increase in plasticizer content.

Acrylic Resins↗