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Synaptic plasticity with discrete state synapses.

Experimental observations on synaptic plasticity at individual glutamatergic synapses from the CA3 Shaffer collateral pathway onto CA1 pyramidal cells in the hippocampus suggest that the transitions in synaptic strength occur among discrete levels at individual synapses [C. C. H. Petersen, Proc. Natl. Acad. Sci. USA 85, 4732 (1998); O'Connor, Wittenberg, and Wang, D. H. O'Connor, Proc. Natl. Acad. Sci. USA (to be published); J. M. Montgomery and D. V. Madison, Trends Neurosci. 27, 744 (2004)]. This happens for both long term potentiation (LTP) and long term depression (LTD) induction protocols. O'Connor, Wittenberg, and Wang have argued that three states would account for their observations on individual synapses in the CA3-CA1 pathway. We develop a quantitative model of this three-state system with transitions among the states determined by a competition between kinases and phosphatases shown by D. H. O'Connor, to be determinant of LTP and LTD, respectively. Specific predictions for various plasticity protocols are given by coupling this description of discrete synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligand gated ion channel conductance changes to a model of postsynaptic membrane potential and associated intracellular calcium fluxes to yield the transition rates among the states. We then present various LTP and LTD induction protocols to the model system and report the resulting whole cell changes in AMPA conductance. We also examine the effect of our discrete state synaptic plasticity model on the synchronization of realistic oscillating neurons. We show that one-to-one synchronization is enhanced by the plasticity we discuss here and the presynaptic and postsynaptic oscillations are in phase. Synaptic strength saturates naturally in this model and does not require artificial upper or lower cutoffs, in contrast to earlier models of plasticity.

Action Potentials↗

Production of prostaglandin E2 and interleukin 1 by mouse peritoneal macrophages stimulated with beta-1,3-D-glucan derivatized plastic beads.

Fluorescein-labelled plastic microbeads, with or without covalently attached beta-1,3-D-glucan, were injected into the peritoneal cavity of mice. Peritoneal cells were subsequently analysed by flow cytometry according to fluorescence and light scatter and separated into fluorescence positive and negative cells. We report that cells from animals treated with glucan-plastic beads produced large amounts of prostaglandin E2 (PGE2) whether the cells actually contained beads or not. On the other hand, cells from animals treated with glucan-plastic beads produced less thymocyte-stimulatory activity--presumably corresponding to interleukin 1 (IL-1)--than cells from control animals treated with commercial latex beads. However, when indomethacin was added, either in vivo or in vitro, cells from animals treated with glucan-plastic beads produced more thymocyte-stimulatory activity than controls. We interpret this to mean that glucan-plastic beads stimulate both IL-1 and PGE2, but that under circumstances where the cellular cyclo-oxygenase is not inhibited, the PGE2 will block IL-1 production.

Animals↗

Platelet function of room temperature platelet concentrates stored in a new plastic material with high gas permeability.

In vitro platelet function during 7 days of storage at room temperature was studied in a conventional polyvinylchloride plastic bag F 76 and in a new plastic bag F 702 which contained as plasticizer a phtalateester analogue. This new material has increased permeability to oxygen and carbon dioxide, and therefore a pH decrease does not occur during 7 days of platelet storage. The decrease of plasma glucose concentration and the increase of plasma lactate in the new bag is less than in the standard plastic currently in use. In vitro platelet function measured as hypotonic shock reaction, aggregation response to ADP and collagen and 14C-serotonine uptake was better than that found with the standard material. The data indicate that the use of the new platelet storage container F702 will permit satisfactory storage for at least 5 days at 22 degrees C. It is suggested that it will even improve the quality, as measured by in vitro tests, of platelets stored up to 72 h compared to the standard plastic.

Blood Platelets↗

Involvement of serotonin in developmental plasticity of kitten visual cortex.

During a critical period of postnatal development, neuronal connections in the kitten visual cortex are susceptible to experience-dependent modifications. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine; 5-HT), the other major neuromodulator in the cerebral cortex, also plays a role in developmental plasticity, we investigated whether interference with serotoninergic transmission in the kitten visual cortex affects ocular dominance (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the serotonin receptor blockers ketanserin and methysergide were infused into the visual cortex of kittens undergoing monocular deprivation. We found that both methods of disrupting serotoninergic transmission reduced OD plasticity. However, to be effective, the receptor blockers ketanserin and methysergide had to be applied in combination, suggesting that coactivation of serotonin receptor subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide hydrolysis, our data suggest that second messengers from the phospholipid pathway may play an important role in developmental plasticity of visual cortex.

5,7-Dihydroxytryptamine↗

Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice.

The cAMP-dependent protein kinase (PKA) signalling pathway has been shown to play an important role in long-term potentiation (LTP) and depression (LTD), and ocular dominance plasticity in the visual cortex. In order to investigate further the involvement of individual PKA subunits in visual cortical plasticity, LTP and LTD in vitro and ocular dominance plasticity in vivo in the developing visual cortex were examined in mice lacking the RII alpha subunit of PKA. Here we show that LTP in layers II/III was decreased in RII alpha knockout mice, but LTD was almost unaffected, and the ocular dominance shift induced by monocular deprivation was also partially blocked. These data provide evidence that RII alpha is involved in LTP and ocular dominance plasticity, and further suggest that different afferent inputs could selectively activate particular subunits of PKA and thereby direct specific aspects of visual cortical plasticity.

Action Potentials↗

Learning in realistic networks of spiking neurons and spike-driven plastic synapses.

We have used simulations to study the learning dynamics of an autonomous, biologically realistic recurrent network of spiking neurons connected via plastic synapses, subjected to a stream of stimulus-delay trials, in which one of a set of stimuli is presented followed by a delay. Long-term plasticity, produced by the neural activity experienced during training, structures the network and endows it with active (working) memory, i.e. enhanced, selective delay activity for every stimulus in the training set. Short-term plasticity produces transient synaptic depression. Each stimulus used in training excites a selective subset of neurons in the network, and stimuli can share neurons (overlapping stimuli). Long-term plasticity dynamics are driven by presynaptic spikes and coincident postsynaptic depolarization; stability is ensured by a refresh mechanism. In the absence of stimulation, the acquired synaptic structure persists for a very long time. The dependence of long-term plasticity dynamics on the characteristics of the stimulus response (average emission rates, time course and synchronization), and on the single-cell emission statistics (coefficient of variation) is studied. The study clarifies the specific roles of short-term synaptic depression, NMDA receptors, stimulus representation overlaps, selective stimulation of inhibition, and spike asynchrony during stimulation. Patterns of network spiking activity before, during and after training reproduce most of the in vivo physiological observations in the literature.

Action Potentials↗

Plasticity-related regulation of the hippocampal proteome.

Plasticity of glutamatergic synapses is considered to be a pivotal mechanism underlying the ability of the CNS to re-configure its neural circuits. A large number of studies have focused on investigating how individual proteins, biochemical pathways and structural processes alter both the induction and maintenance of synaptic plasticity. However, it is likely that synaptic plasticity involves temporally and spatially coordinated regulation of multiple protein complexes within the activated neural circuit. By using a global proteomics-based approach we have now been able to reveal that highly diverse protein classes exhibit altered expression in response to both the activation of glutamate receptors and the induction of long-term potentiation (LTP) of glutamatergic synaptic strength in the hippocampus; a brain area where plastic synaptic modification is believed to be key to cognitive processes, such as spatial learning. Of the 2946 resolvable protein spots detected in this study, 79 (2.7%) were significantly altered in abundance in response to 100 microM glutamate application (all P < 0.05). The majority (56 out of 79) of these changes were due to the activation of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor. Likewise, the induction of LTP was associated with an altered abundance of 2.4% of the detectable proteome during the early (10 min) phase and 1.7% during the late (4 h) phase of its development. Observed changes in temporal and protein class-specific patterns of expression depict a widespread shift from metabolic to structural protein alteration as the plasticity process matures.

2-Amino-5-phosphonovalerate↗

Use of yellow plastic food wrap to retard composite resin polymerization.

BACKGROUND: Dental chair lights can rapidly polymerize light-reactive composites beyond the point of workability, preventing adequate time for the shaping and sculpting of large direct composite restorations. PURPOSE: The purpose of this study was to determine whether yellow plastic food wrap placed over a dental chair light would perceptibly retard the polymerization rate of a light-cured composite (Esthet-X, shade A1, Dentsply/Caulk, Milford, DE, USA). MATERIALS AND METHODS: Zero, one, and two thicknesses of yellow plastic food wrap (Reynolds Metals Company, Richmond, VA, USA) were, in turn, used in the following scenarios: (1) placed in a spectrophotometer and compared for percentage transmission of 470 nm light; (2) placed over a curing unit light wand and compared for milliwatts of output on a radiometer; (3) placed over a dental chair light positioned 64 cm from 0.22 mm thick composite specimens, with Fourier Transform Infrared Spectrometry readings made every 40 seconds to measure degree of composite polymerization; (4) placed over a dental chair light positioned 64 cm from a direct veneer preparation (clinical simulation), which was then restored by four experienced clinicians who reported working times. RESULTS: Results for the scenarios were as follows: (1) zero sheets 100%, one sheet 34%, two sheets 6%; (2) zero sheets 580 mW, one sheet 190 mW, two sheets 20 mW; (3) percent conversion at 80 seconds--zero sheets 8%, one sheet 0.65%, two sheets 0.76%; percent conversion at 120 seconds--zero sheets 19.11%, one sheet 12.22%, two sheets 0.42%; (4) mean working times--zero sheets 34 seconds, one sheet 72 seconds, two sheets 155 seconds. CONCLUSIONS: Yellow plastic food wrap placed over a dental chair light markedly extended the working time of a light-cured composite in each of four assessments performed. Two sheets of plastic wrap were more than twice as effective as one sheet. CLINICAL SIGNIFICANCE: The suggested filtering technique with yellow plastic wrap placed over a dental chair light is a highly effective, expedient, and inexpensive method for increasing the working time of light-cured composites.

Color↗

Presynaptic plasticity at two giant auditory synapses in normal and deaf mice.

Large calyceal synapses are often regarded as simple relay points, built for high-fidelity and high-frequency synaptic transmission and a minimal requirement for synaptic plasticity, but this view is oversimplified. Calyceal synapses can exhibit surprising activity-dependent developmental plasticity. Here we compare basal synaptic transmission and activity-dependent plasticity at two stereotypical calyceal synapses in the auditory pathway, the endbulb and the calyx of Held. Basal synaptic transmission was more powerful at the calyx than the endbulb synapse: the amplitude of evoked AMPA receptor-mediated excitatory postsynaptic currents (eEPSCs) was significantly greater at the calyx, as were the release probability, and the number of release sites. The quantal amplitude was smaller at the calyx, consistent with the smaller amplitude of spontaneous miniature EPSCs at this synapse. High-frequency trains of stimuli revealed that the calyx had a larger readily releasable pool of vesicles (RRP), less tetanic depression and less asynchronous transmitter release. Activity-dependent synaptic plasticity was assessed in congenitally deaf mutant mice (dn/dn). Previously we showed that a lack of synaptic activity in deaf mice increases synaptic strength at the endbulb of Held via presynaptic mechanisms. In contrast, we have now found that deafness does not affect synaptic transmission at the calyx synapse, as eEPSC and mEPSC amplitude, release probability, number of release sites, size of RRP, tetanic depression and asynchronous release were unchanged compared to normal mice. Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse.

Animals↗

A conducting plastic simulating brain tissue.

A new conducting plastic has been composed which accurately simulates the photon and neutron absorption properties of brain tissue. This tissue-equivalent (TE) plastic was formulated to match the hydrogen and nitrogen constituents recommended by ICRU Report #44 for brain tissue. Its development was initiated by the inability of muscle tissue-equivalent plastic to closely approximate brain tissue with respect to low-energy neutron interactions. This new plastic is particularly useful as an electrode in TE dosimetry devices for boron neutron capture therapy (BNCT), which utilizes low-energy neutrons for radiotherapy of the brain. Absorbed dose measurements in a clinical BNCT beam using a proportional counter constructed from this TE plastic show good agreement with Monte Carlo calculations.

Boron Neutron Capture Therapy↗

Monte Carlo calculations of the absorbed dose and energy dependence of plastic scintillators.

Detector systems using plastic scintillators can provide instantaneous measurements with high spatial resolution in many applications including small field and high dose gradient field applications. Energy independence and water equivalence are important dosimetric properties that determine whether a detector will be useful in a clinical setting. Using Monte Carlo simulations, we calculated the energy dependence of plastic scintillators when exposed to photon beams in the radiotherapeutic range. These calculations were performed for a detector comprised of a BC-400 plastic scintillator surrounded by a polystyrene wall. Our results showed the plastic scintillation detector to be nearly energy independent over a range of energies from 0.5 to 20 MeV. The ratio of the dose absorbed by the scintillator to that absorbed by water was nearly a constant, approximately equal to 0.98 over the entire energy range of interest. These results confirm the water equivalence of the plastic scintillation detector and are in very good agreement with earlier results obtained using Burlin cavity theory.

Computer Simulation↗

Requirement for alpha-CaMKII in experience-dependent plasticity of the barrel cortex.

The mammalian sensory neocortex exhibits experience-dependent plasticity such that neurons modify their response properties according to changes in sensory experience. The synaptic plasticity mechanism of long-term potentiation requiring calcium-calmodulin-dependent kinase type II (CaMKII) could underlie experience-dependent plasticity. Plasticity in adult mice can be induced by changes in the patterns of tactile input to the barrel cortex. This response is strongly depressed in adult mice that lack the gene encoding alpha-CaMKII, although adolescent animals are unaffected. Thus, alpha-CaMKII is necessary either for the induction or for the expression of plasticity in adult mice.

Animals↗

Plasticizers increase adhesion of the deteriogenic fungus Aureobasidium pullulans to polyvinyl chloride.

Initial adhesion of fungi to plasticized polyvinyl chloride (pPVC) may determine subsequent colonization and biodeterioration processes. The deteriogenic fungus Aureobasidium pullulans was used to investigate the physicochemical nature of adhesion to both unplasticized PVC (uPVC) and pPVC containing the plasticizers dioctyl phthalate (DOP) and dioctyl adipate (DOA). A quantitative adhesion assay using image analysis identified fundamental differences in the mechanism of adhesion of A. pullulans blastospores to these substrata. Adhesion to pPVC was greater than that to uPVC by a maximum of 280% after a 4-h incubation with 10(8) blastospores ml(-1). That plasticizers enhance adhesion to PVC was confirmed by incorporating a dispersion of both DOA and DOP into the blastospore suspension. Adhesion to uPVC was increased by up to 308% in the presence of the dispersed plasticizers. Hydrophobic interactions were found to dominate adhesion to uPVC because (i) a strong positive correlation was observed between substratum hydrophobicity (measured by using a dynamic contact angle analyzer) and adhesion to a range of unplasticized polymers including uPVC, and (ii) neither the pH nor the electrolyte concentration of the suspension buffer, both of which influence electrostatic interactions, affected adhesion to uPVC. In contrast, adhesion to pPVC is principally controlled by electrostatic interactions. Enhanced adhesion to pPVC occurred despite a relative reduction of 13 degrees in the water contact angle of pPVC compared to that of uPVC. Furthermore, adhesion to pPVC was strongly dependent on both the pH and electrolyte concentration of the suspension medium, reaching maximum levels at pH 8 and with an electrolyte concentration of 10 mM NaCl. Plasticization with DOP and DOA therefore increases adhesion of A. pullulans blastospores to pPVC through an interaction mediated by electrostatic forces.

Ascomycota↗

Exposure to styrene and chronic health effects: mortality and incidence of solid cancers in the Danish reinforced plastics industry.

OBJECTIVES: To study the occurrence of non-malignant diseases and solid cancers in workers exposed to styrene in the Danish reinforced plastics industry. METHODS: All 36,610 workers of 386 reinforced plastics companies and 14,293 workers not exposed to styrene from similar industries were followed up from 1970 to 1990. This industry is characterised by simple exposure conditions, exposure to high concentrations of styrene, and a high proportion of small companies, and the exposure assessment was based on experts' classification on a company level. The mortality from non-malignant causes and the incidence of solid cancers were compared with the national rates. Poisson models were used for internal comparisons. RESULTS: A total of 3031 deaths and 1134 newly diagnosed cases of solid cancer were reported in the workers in the reinforced plastics industry. In companies where 50% or more of the workers produced reinforced plastics an increased mortality rate ratio (MRR) for degenerative disorders of the nervous system (multiple sclerosis, parkinsonism, and motor neurone disease; MRR 1.8, 16 cases, 95% confidence interval (95% CI) 0.9-3.8) and an increased incidence rate ratio (IRR) for pancreatic cancer (IRR 2.2, 17 cases, 95% CI 1.1-4.5) was found. For both disease categories increased occurrence was also found among long term workers, workers of the 1960s (the period with the highest exposure to styrene), and workers with a latent period of more than 10 years after the start of employment. No other non-malignant diseases or solid cancers showed these patterns. CONCLUSION: The findings have to be interpreted with caution, due to the company based exposure assessment, but the possible association between exposures in the reinforced plastics industry, mainly styrene, and degenerative disorders of the nervous system and pancreatic cancer, deserves attention.

Cause of Death↗

Synaptic plasticity and memory: an evaluation of the hypothesis.

Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.

Amygdala↗

Cerebellum-dependent learning: the role of multiple plasticity mechanisms.

The cerebellum is an evolutionarily conserved structure critical for motor learning in vertebrates. The model that has influenced much of the work in the field for the past 30 years suggests that motor learning is mediated by a single plasticity mechanism in the cerebellum: long-term depression (LTD) of parallel fiber synapses onto Purkinje cells. However, recent studies of simple behaviors such as the vestibulo-ocular reflex (VOR) indicate that multiple plasticity mechanisms contribute to cerebellum-dependent learning. Multiple plasticity mechanisms may provide the flexibility required to store memories over different timescales, regulate the dynamics of movement, and allow bidirectional changes in movement amplitude. These plasticity mechanisms must act in combination with appropriate information-coding strategies to equip motor-learning systems with the ability to express learning in correct contexts. Studies of the patterns of generalization of motor learning in the VOR provide insight about the coding of information in neurons at sites of plasticity. These principles emerging from studies of the VOR are consistent with results concerning more complex behaviors and thus may reflect general principles of cerebellar function.

Animals↗

Endocannabinoid-mediated synaptic plasticity in the CNS.

Changes in synaptic efficacy are thought to be crucial to experience-dependent modifications of neural function. The diversity of mechanisms underlying these changes is far greater than previously expected. In the last five years, a new class of use-dependent synaptic plasticity that requires retrograde signaling by endocannabinoids (eCB) and presynaptic CB1 receptor activation has been identified in several brain structures. eCB-mediated plasticity encompasses many forms of transient and long-lasting synaptic depression and is found at both excitatory and inhibitory synapses. In addition, eCBs can modify the inducibility of non-eCB-mediated forms of plasticity. Thus, the eCB system is emerging as a major player in synaptic plasticity. Given the wide distribution of CB1 receptors in the CNS, the list of brain structures and synapses expressing eCB-mediated plasticity is likely to expand.

Animals↗

Common bile duct obstruction due to malignancy: treatment with plastic versus metal stents.

PURPOSE: To compare the clinical efficacy and treatment costs of plastic versus metal biliary stents. MATERIALS AND METHODS: In a randomized trial, 101 patients with malignant common bile duct obstruction underwent transhepatic stent implantation and were followed up until death. Patients were stratified into risk and nonrisk groups. Forty-nine patients received 12-F plastic stents, and 52 received expandable metal stents. Plastic endoprostheses were placed in a two-step procedure; metal stent, in a single procedure. Kaplan-Meier analyses were used to compare patient survival and stent patency rates. RESULTS: The 30-day mortality rate was significantly lower for metal stents (five of 52 [10%]) than plastic stents (12 of 49 [24%]; P = .05). The obstruction rate was 19% (10 of 52; median patency, 272 days) for metal stents and 27% for plastic stents (13 of 49; median patency, 96 days; P < .01). Median time until death or obstruction was longer for metal stents (122 vs 81 days; P < .01). Placement of metal stents was associated with shorter hospital stay (10 vs 21 days; P < .01) and lower cost ($7,542 vs $12,129; P < .01). CONCLUSION: Use of self-expanding metal stents appears to show substantial benefits for patients and to be cost-effective.

Aged↗