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Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing.

AIMS/HYPOTHESIS: Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. METHODS: Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocin-diabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). RESULTS: Statistically significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218% of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92%). In non-diabetic aged rats synaptic responses were 149 and 93% of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75% in aged diabetic rats. CONCLUSION/INTERPRETATION: Both diabetes and ageing affect learning and hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact.

Aging↗

Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical studies.

RATIONALE: Research over the past decade demonstrating that NMDA receptor antagonists have the ability to inhibit opiate tolerance, sensitization and physical dependence has led to the suggestion that NMDA receptors may have a critical role in opiate-induced neural and behavioral plasticity. However, there have been suggestions that the effects of NMDA receptor antagonists on these phenomena result from non-specific behavioral or pharmacological effects, rather than from a specific inhibition of plasticity. OBJECTIVES: To review the literature in order to explore whether the effects of NMDA receptor antagonists on opiate-induced changes in behavior are best accounted for by an inhibition of neural and behavioral plasticity, or if alternative explanations might better account for the results. RESULTS: The effects of NMDA receptor antagonists on the development of tolerance to opiate analgesia and the development of opiate physical dependence do not appear to be due to confounding behavioral effects produced by high doses of NMDA receptor antagonists, "side-effects" of a particular drug or drug class, blockade of associative learning processes, or state-dependency. Results on tolerance and sensitization to the locomotor effects of morphine are more mixed and controversial; however, there is evidence suggesting that NMDA receptor antagonists may inhibit these phenomena in a similar manner. CONCLUSIONS: NMDA receptor antagonists appear to inhibit the neural plasticity underlying some forms of opiate tolerance, sensitization and physical dependence, suggesting that NMDA receptors are involved in the development of these drug-induced changes in behavior. Further research will help to determine the neural mechanisms responsible for these phenomena, and the therapeutic potential for drugs acting on the NMDA receptor complex in the treatment of pain and addiction.

Animals↗

Properties of long-term synaptic plasticity and metaplasticity in organotypic slice cultures of rat hippocampus.

The aim of this study was to investigate whether synaptic plasticity and metaplasticity in slice cultures of the young rat hippocampus were comparable to previously reported synaptic plasticity and metaplasticity in acute adult hippocampal slices. This is relevant since differences do exist between the preparations as a result of age and the ex vivo maintenance. We prepared and maintained slice cultures from 5- to 6-day-old rats according to the porous membrane method. After 12-16 days in vitro, extracellular low-frequency stimulation (LFS) and high-frequency stimulation (HFS) protocols were applied to the Schaffer collaterals, and extracellular field potentials were recorded in area CA1. LFS and HFS induced long-term depression (LTD) and long-term potentiation (LTP), respectively. LTP could be reversed by LFS, as could LTD by HFS 60 min after induction. Plotting the amount of LTD and LTP versus stimulation protocol demonstrated frequency-dependence of the sign and extent of plasticity. Priming activation of group 1 metabotropic glutamate receptors (mGluRs) with DHPG facilitated subsequent LTP, revealing a metaplastic effect similar to that observed in acute slices. Immunohistochemistry for group 1 mGluR subtypes mGluR1alpha and mGluR5 showed both receptors to be present in these cultures. We conclude that synaptic plasticity and mGluR-mediated metaplasticity are largely comparable to those effects found in acute in vitro techniques.

Animals↗

Induction of plasticity in the dominant and non-dominant motor cortices of humans.

There are clear hemispheric differences in the human motor system. Studies using magnetic resonance morphometry have shown that representation of hand muscles is larger in the dominant hemisphere than the non-dominant hemisphere. There is some limited evidence of electrophysiological differences between hemispheres. For example, it has been reported recently that there is less intracortical inhibition in the dominant hemisphere than the non-dominant hemisphere, and it has been hypothesised that this reduction in inhibition may facilitate use-dependent plasticity in the dominant motor cortex. In the present study we examined this hypothesis in human subjects by examining plasticity induction in both dominant and non-dominant hemispheres using an experimental paradigm known to induce motor cortical plasticity, namely paired associative stimulation (PAS). Additionally, we investigated changes in dominant and non-dominant hand performance on a simple ballistic training task. Short-interval intracortical inhibition (SICI) was also measured for both dominant and non-dominant hands at a range of conditioning intensities. There was significantly less SICI in the dominant motor cortical hand area than in the non-dominant hand area. PAS induced a significant, and similar, increase in motor cortical excitability in both the dominant and non-dominant hemispheres. Motor training resulted in significant performance improvement in both dominant and non-dominant hands. However, there was significantly more improvement in the non-dominant hand. The results from these studies provide some further evidence of electrophysiological differences between the motor cortices of the two hemispheres. Additionally, these findings offer no support for the hypothesis that the dominant hemisphere is positioned more favourably, due to decreased inhibitory tone, than the non-dominant hemisphere for use-dependent plasticity.

Adolescent↗

The scientific contributions of British Plastic Surgeons to the Revue de Chirurgie Plastique and the Revue de Chirurgie Structive, Brussels (1931-1938).

In 1931, Maurice Coelst, M.D. from Brussels started the publication of the first international journal of plastic surgery ever published: the Revue de Chirurgie Plastique (1931-1934), which eventually became the Revue de Chirurgie Structive (1935-1938). In 1936, he established the first European Society of Structive Surgery, which held its first congress in Brussels. Further congresses were held in London in 1937 and in Milan in 1938. It is the collaboration and the participation of British plastic surgeons in this Society, this journal, and these meetings that I want to stress, because I am firmly convinced that these documents fill a gap in the history of Plastic Surgery in Great Britain, since--as far as I know--no detailed information concerning this period was ever published in Plastic Surgery literature.

Belgium↗

U.S. plastic surgeons who contributed to the Revue de Chirurgie Plastique and the Revue de Chirurgie Structive (1931-1938): "Giants" in our specialty.

The Revue de Chirurgie Plastique and the Revue de Chirurgie Structive, Brussels (1931-1938), edited by Maurice Coelst, M.D. from Brussels, were the first, full-fledged medical publications specifically devoted to plastic, reconstructive, and aesthetic surgery. Publishing original articles by J.W. Maliniac, J. Eastman Sheehan, and brief summaries of papers read at plastic surgery societies by C.R. Straatsma, L.A. Peer, G. Aufricht, and other well-known American plastic surgeons, these Revues drew attention to surgeons, most of whom were responsible for organizing the American Society of Plastic and Reconstructive Surgeons in 1931, the same year in which the Revue de Chirurgie Plastique first appeared.

Belgium↗

Plastic solutions for orthopaedic problems.

INTRODUCTION: Infection and exposure of the implant may occur in 1-12% of patients operated on for arthroplasty or osteosynthesis. Variables such as tissue viability, presence of infection, exposure of osteosynthesis material and patient-related factors contribute to the lack of general consensus regarding the management of these defects. MATERIALS AND METHODS: Between January 1999 and January 2001, six patients were treated for complex soft-tissue defects following various orthopaedic procedures at the Department of Plastic Surgery in the Slotervaartziekenhuis in Amsterdam, a rheuma-orthopaedic orientated hospital. All patients were initially treated by radical debridement and vacuum-assisted closure (VAC) system of the wound. After 1 week, this was followed by transplantation of a pedicled or free flap to cover the defect. We studied the medical history, initial orthopaedic procedure, wound treatment, transplanted flap and outcome of plastic surgery in this group. RESULTS: Plastic surgical intervention led to wound closure in all cases. In only one case was the osteosynthesis material removed because of osteomyelitis. CONCLUSIONS: We conclude that the earlier coverage with vital tissue is obtained, the lower the incidence of infection. Early consultation by a plastic surgeon will increase a positive outcome of treatment of complex tissue defects.

Adult↗

Spike timing and synaptic plasticity in the premotor pathway of birdsong.

The neural circuits of birdsong appear to utilize specific time delays in their operation. In particular, the anterior forebrain pathway (AFP) is implicated in an approximately 40- to 50- ms time delay, DeltaT, playing a role in the relative timing of premotor signals from the nucleus HVc to the nucleus robust nucleus of the archistratium (RA) and control/learning signals from the nucleus lateral magnocellular nucleus of the anterior neostratium (lMAN) to RA. Using a biophysical model of synaptic plasticity based on experiments on mammalian hippocampal and neocortical pyramidal neurons, we propose an understanding of this approximately 40- to 50- ms delay. The biophysical model describes the influence of Ca2+ influx into the postsynaptic RA cells through NMDA and AMPA receptors and the induction of LTP and LTD through complex metabolic pathways. The delay, DeltaT, between HVc --> RA premotor signals and lMAN --> RA control/learning signals plays an essential role in determining if synaptic plasticity is induced by signaling from each pathway into RA. If DeltaT is substantially larger than 40 ms, no plasticity is induced. If DeltaT is much less than 40 ms, only potentiation is expected. If DeltaT approximately 40 ms, the sign of synaptic plasticity is sensitive to DeltaT. Our results suggest that changes in DeltaT may influence learning and maintenance of birdsong. We investigate the robustness of this result to noise and to the removal of the Ca2+ contribution from lMAN --> RA NMDA receptors.

Action Potentials↗

Local learning rules: predicted influence of dendritic location on synaptic modification in spike-timing-dependent plasticity.

Recent indirect experimental evidence suggests that synaptic plasticity changes along the dendrites of a neuron. Here we present a synaptic plasticity rule which is controlled by the properties of the pre- and postsynaptic signals. Using recorded membrane traces of back-propagating and dendritic spikes we demonstrate that LTP and LTD will depend specifically on the shape of the postsynaptic depolarization at a given dendritic site. We find that asymmetrical spike-timing-dependent plasticity (STDP) can be replaced by temporally symmetrical plasticity within physiologically relevant time windows if the postsynaptic depolarization rises shallow. Presynaptically the rule depends on the NMDA channel characteristic, and the model predicts that an increase in Mg(2+) will attenuate the STDP curve without changing its shape. Furthermore, the model suggests that the profile of LTD should be governed by the postsynaptic signal while that of LTP mainly depends on the presynaptic signal shape.

Action Potentials↗

A model of activity-dependent anatomical inhibitory plasticity applied to the mammalian auditory system.

We construct a model of activity-dependent, anatomical inhibitory plasticity. We apply the model to the mammalian auditory system. Specifically, we model the activity-dependent topographic refinement of inhibitory projections in the auditory brain stem, and we construct an anatomically abstract model of binaural band formation in the primary auditory cortex involving the segregation of different populations of inhibitory and excitatory afferents. Issues raised and predictions made include the nature of interactions between excitatory and inhibitory afferents innervating the same population of target cells, and the possibility that pharmacological manipulations of the developing primary auditory cortex might induce a shift in the periodicity of binaural bands. Any model of inhibitory plasticity must confront the issue of postulating mechanisms underlying such plasticity. In order to attempt to understand, at least theoretically, what the mechanisms underlying inhibitory plasticity might be, we propose the existence of a new class of neurotrophic factors that promote neurite outgrowth from and mediate competitive interactions between inhibitory afferents. We suppose that such factors are up-regulated by hyperpolarisation and down-regulated by depolarisation. Furthermore, we suppose that their activity-dependent release from target cells depends on Cl- influx. Such factors are therefore assumed to be the physiological inverse of such factors as nerve growth factor and brain-derived neurotrophic factor, which are up-regulated by depolarisation and down-regulated by hyperpolarisation, with their activity-dependent release depending on Na+, and not Ca2+, influx.

Animals↗

Stability of complex spike timing-dependent plasticity in cerebellar learning.

Dynamics of spike-timing dependent synaptic plasticity are analyzed for excitatory and inhibitory synapses onto cerebellar Purkinje cells. The purpose of this study is to place theoretical constraints on candidate synaptic learning rules that determine the changes in synaptic efficacy due to pairing complex spikes with presynaptic spikes in parallel fibers and inhibitory interneurons. Constraints are derived for the timing between complex spikes and presynaptic spikes, constraints that result from the stability of the learning dynamics of the learning rule. Potential instabilities in the parallel fiber synaptic learning rule are found to be stabilized by synaptic plasticity at inhibitory synapses if the inhibitory learning rules are stable, and conditions for stability of inhibitory plasticity are given. Combining excitatory with inhibitory plasticity provides a mechanism for minimizing the overall synaptic input. Stable learning rules are shown to be able to sculpt simple-spike patterns by regulating the excitability of neurons in the inferior olive that give rise to climbing fibers.

Action Potentials↗

Metal-enhanced fluorescence from plastic substrates.

We report the first findings of Metal-Enhanced Fluorescence (MEF) from modified plastic substrates. In the past several years our laboratories have reported the favorable effects of fluorophores in close proximity to silver nanoparticles. These effects include, enhanced fluorescence intensities, (increased detectability), and reduced lifetimes, (enhanced fluorophore photostability). All of these reports have featured silver nanostructures and fluorophores which have been immobilized onto clean glass or quartz surfaces. In this report we show how plastic surfaces can be modified to obtain surface functionality, which in turn allows for silver deposition and therefore metal-enhanced fluorescence of fluorophores positioned above the silver using a protein spacer. Our findings show that plastic substrates are ideal surfaces for metal-enhanced phenomena, producing similar enhancements as compared to clean glass surfaces. Subsequently, we speculate that plastic substrates for MEF will find common place, as compared to the more expensive and less versatile traditional silica based supports.

Fluorescence↗

New concepts in surgery of WHO grade II gliomas: functional brain mapping, connectionism and plasticity--a review.

Despite a recent literature supporting the impact of surgery on the natural history of low-grade glioma (LGG), the indications of resection still remain a matter of debate, especially because of the frequent location of these tumors within eloquent brain areas - thus with a risk to induce a permanent postoperative deficit. Therefore, since the antagonist nature of this surgery is to perform the most extensive glioma removal possible, while preserving the function and the quality of life, new concepts were recently applied to LGG resection in order to optimize the benefit/risk ratio of the surgery.First, due to the development of functional mapping methods, namely perioperative neurofunctional imaging and intrasurgical direct electrical stimulation, the study of cortical functional organization is currently possible for each patient - in addition to an extensive neuropsychological assessment. Such knowledge is essential because of the inter-individual anatomo-functional variability, increased in tumors due to cerebral plasticity phenomena. Thus, brain mapping enables to envision and perform a resection according to individual functional boundaries.Second, since LGG invades not only cortical but also subcortical structures, and shows an infiltrative progression along the white matter tracts, new techniques of anatomical tracking and functional mapping of the subcortical white matter pathways were also used with the goal to study the individual effective connectivity - which needs imperatively to be preserved during the resection.Third, the better understanding of brain plasticity mechanisms, induced both by the slow-growing LGG and by the surgery itself, were equally studied in each patient and applied to the surgical strategy by incorporating individual dynamic potential of reorganization into the operative planning. The integration of these new concepts of individual functional mapping, connectivity and plastic potential to the surgery of LGG has allowed an extent of surgical indications, an optimization of the quality of resection (neuro-oncological benefit), and a minimization of the risk of sequelae (benefit on the quality of life). In addition, such a strategy has also fundamental applications, since it represents a new door to the connectionism and cerebral plasticity.

Brain Mapping↗

Effects of synaptic antagonists on perforant path paired-pulse plasticity: differentiation of pre- and postsynaptic antagonism.

The effects of different synaptic antagonists on paired-pulse plasticity of medial perforant path responses were studied in rat hippocampal slices. Baclofen reduces the response to activation of the perforant path, but does not have the same net effect on the first and second responses to paired stimulation: baclofen lessens the percent paired-pulse depression of medial perforant path responses. Furthermore, at doses that reduced the control medial perforant path response by half, paired-pulse plasticity changed from paired-pulse depression to paired-pulse potentiation. A similar effect on medial perforant path paired-pulse plasticity is produced by decreasing extracellular calcium concentration. Kynurenic acid reduces the first and second responses to paired stimulation proportionately the same, and, therefore, has no effect on the percent paired-pulse depression. These results suggest that baclofen acts presynaptically to reduce the synaptic response, whereas kynurenate acts postsynaptically. Adenosine was also found to be a potent antagonist of medial perforant path responses, with effects on paired-pulse plasticity similar to baclofen: a new synaptic antagonist, N-p-chlorobenzoyl-piperazine-2,3-dicarboxylate, was found to have effects like kynurenate, suggesting that it is also a postsynaptic receptor blocker.

Adenosine↗

Robust synaptic plasticity of striatal cells following partial deafferentation.

Partial ablation of the cerebral cortical input to the neostriatum generates a rapid lasting effect on the size of remaining synaptic sites. The neocortex was lesioned in adult rats and the neostriatum was analyzed for effects on remaining spines of principal cells during the period from 2 to 40 days. There was an increase in the size of spine heads, boutons and synaptic contact sites. The spine heads became very complex and a corresponding bouton enlargement was accompanied by an increase in the number of synaptic vesicles. By two days, the average profile length of postsynaptic membrane densities (PSDs) had increased by 25% representing an equivalent 50% increase in synaptic contact area. The number of synaptic sites was reduced on each principal neuron of the lesioned group. Comparison of the number of sites per unit volume to their average contact area revealed a reciprocal relationship indicating a conservation in the total synaptic contact area on each neuron. This effect was consistent for all postsurgical days. The lack of a significant return of synaptic number by 40 days indicates that axonal sprouting is not a major factor in neuronal plasticity in the adult striatum. The rapid increase in the size of spines, boutons and synaptic sites at remaining connections suggests that dendrites are the first to initiate the plasticity response in adult neurons through postsynaptic attachments and their corresponding receptor structure. The underlying mechanism of this plasticity may be through a conservation of macromolecules forming postsynaptic membrane specializations on target neurons. Remaining axons appear to follow the dendritic response with a plasticity generating presynaptic appositional specializations to match the contact area of the postsynaptic site.

Animals↗

Structure and plasticity of newly formed adult synapses: a morphometric study in the rat hippocampus.

Increasing evidence suggests that synaptic structure represents a plastic feature of the neuron, although the plastic nature of newly formed and existing adult synapses has not yet been fully characterized. Following ipsilateral entorhinal cortical lesions, the rat dentate gyrus offers an excellent model for studying synaptogenesis and plasticity in the adult central nervous system. Unilateral entorhinal lesions were performed in young adult male rats. Synaptic counts and structural features were quantified at 3, 6, 10, 15, and 30 days post-lesion. The lesions resulted in an 88% synaptic loss in the denervated dentate middle molecular layer, which was followed by a period of rapid synaptogenesis. Synaptic element size decreased during the period of maximal synaptogenesis, which was associated with a peak in the presence of non-vesicular and perforated synapses. Following this period, synapses showed a gradual increase in the size of their pre- and postsynaptic elements. These data support the suggestion that newly formed adult synapses have smaller synaptic components than existing adult synapses (resembling synapses seen during development), and increase in size over time with usage. The results are discussed in terms of synaptic structural development and plasticity in the adult central nervous system.

Animals↗

Kinetics of the aeration of ethylene-oxide sterilized plastics.

The aeration of ethylene-oxide (EO) sterilized medical plastic materials is dealth with mathematically, and subsequently the model found is used for calculation of the EO diffusion coefficient in various plastics with the composition and temperature as variables. Absorption and dissolution of EO in various plastic materials are measured at varying concentrations of EO, temperatures and compositions of plastics. The mathematical model is used to evaluate the EO desorption from medical devices under different physico-chemical conditions as well as in vivo. EO analysis methods are evaluated on the basis of the model and are compared with experimental results.

Diffusion↗

Surface spectroscopic characterization of titanium implants after separation from plastic-embedded tissue.

The method of plastic embedding of tissue and implant and subsequent separation of plastic and implant for preparing sections of tissue adjacent to solid metallic implants relies on a successful separation of the embedment and the implant. In this work, the surface of machined Ti implants has been analysed in order to investigate to what extent plastic remnants exist on the implant after separation. SEM and AES analyses show that at least 70% of the implant surface is free of plastic remnants to a proximity of 10 nm or less from the implant surface. The method is simple and suitable for both light and transmission electron microscopy of the interface tissue.

Bone Screws↗