87 research outputs found

    A transcription-dependent increase in miniature EPSC frequency accompanies late-phase plasticity in cultured hippocampal neurons

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    <p>Abstract</p> <p>Background</p> <p>The magnitude and longevity of synaptic activity-induced changes in synaptic efficacy is quantified by measuring evoked responses whose potentiation requires gene transcription to persist for more than 2-3 hours. While miniature EPSCs (mEPSCs) are also increased in amplitude and/or frequency during long-term potentiation (LTP), it is not known how long such changes persist or whether gene transcription is required.</p> <p>Results</p> <p>We use whole-cell patch clamp recordings from dissociated hippocampal cultures to characterise for the first time the persistence and transcription dependency of mEPSC upregulation during synaptic potentiation. The persistence of recurrent action potential bursting in these cultures is transcription-, translation- and NMDA receptor-dependent thus providing an accessible model for long-lasting plasticity. Blockade of GABA<sub>A</sub>-receptors with bicuculline for 15 minutes induced action potential bursting in all neurons and was maintained in 50-60% of neurons for more than 6 hours. Throughout this period, the frequency but neither the amplitude of mEPSCs nor whole-cell AMPA currents was markedly increased. The transcription blocker actinomycin D abrogated, within 2 hours of burst induction, both action potential bursting and the increase in mEPSCs. Reversible blockade of action potentials during, but not after this 2 hour transcription period suppressed the increase in mEPSC frequency and the recovery of burst activity at a time point 6 hours after induction.</p> <p>Conclusion</p> <p>These results indicate that increased mEPSC frequency persists well beyond the 2 hour transcription-independent phase of plasticity in this model. This long-lasting mEPSC upregulation is transcription-dependent and requires ongoing action potential activity during the initial 2 hour period but not thereafter. Thus mEPSC upregulation may underlie the long term, transcription-dependent persistence of action potential bursting. This provides mechanistic insight to link gene candidates already identified by gene chip analysis to long lasting plasticity in this in vitro model.</p

    First Magnetic Resonance Imaging-Guided Aortic Stenting and Cava Filter Placement Using a Polyetheretherketone-Based Magnetic Resonance Imaging-Compatible Guidewire in Swine: Proof of Concept

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    The purpose of this study was to demonstrate feasibility of percutaneous transluminal aortic stenting and cava filter placement under magnetic resonance imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI-compatible guidewire. Percutaneous transluminal aortic stenting and cava filter placement were performed in 3 domestic swine. Procedures were performed under MRI-guidance in an open-bore 1.5-T scanner. The applied 0.035-inch guidewire has a PEEK core reinforced by fibres, floppy tip, hydrophilic coating, and paramagnetic markings for passive visualization. Through an 11F sheath, the guidewire was advanced into the abdominal (swine 1) or thoracic aorta (swine 2), and the stents were deployed. The guidewire was advanced into the inferior vena cava (swine 3), and the cava filter was deployed. Postmortem autopsy was performed. Procedural success, guidewire visibility, pushability, and stent support were qualitatively assessed by consensus. Procedure times were documented. Guidewire guidance into the abdominal and thoracic aortas and the inferior vena cava was successful. Stent deployments were successful in the abdominal (swine 1) and thoracic (swine 2) segments of the descending aorta. Cava filter positioning and deployment was successful. Autopsy documented good stent and filter positioning. Guidewire visibility through applied markers was rated acceptable for aortic stenting and good for venous filter placement. Steerability, pushability, and device support were good. The PEEK-based guidewire allows either percutaneous MRI-guided aortic stenting in the thoracic and abdominal segments of the descending aorta and filter placement in the inferior vena cava with acceptable to good device visibility and offers good steerability, pushability, and device suppor

    Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability

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    Neuroprotection can be induced by low doses of NMDA, which activate both synaptic and extrasynaptic NMDA receptors. This is in apparent contradiction with our recent findings that extrasynaptic NMDA receptor signaling exerts a dominant inhibitory effect on prosurvival signaling from synaptic NMDA receptors. Here we report that exposure to low preconditioning doses of NMDA results in preferential activation of synaptic NMDA receptors because of a dramatic increase in action potential firing. Both acute and long-lasting phases of neuroprotection in the face of apoptotic or excitotoxic insults are dependent on this firing enhancement. Key mediators of synaptic NMDA receptor-dependent neuroprotection, phosphatidylinositol 3 kinase-Akt (PI3 kinase-Akt) signaling to Forkhead box subgroup O (FOXO) export and glycogen synthase kinase 3β (GSK3β) inhibition and cAMP response element-binding protein-dependent (CREB-dependent) activation of brain-derived neurotrophic factor (BDNF), can be induced only by low doses of NMDA via this action potential-dependent route. In contrast, NMDA doses on the other side of the toxicity threshold do not favor synaptic NMDA receptor activation because they strongly suppress firing rates below baseline. The classic bell-shaped curve depicting neuronal fate in response to NMDA dose can be viewed as the net effect of two antagonizing (synaptic vs extrasynaptic) curves: via increased firing the synaptic signaling dominates at low doses, whereas firing becomes suppressed and extrasynaptic signaling dominates as the toxicity threshold is crossed

    Eigenschaften und Auswirkungen von Oberflächenwellen auf die Litoralzone eines großen Sees (Bodensee)

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    This thesis is the first long-term investigation that gives a detailed characterization of the surface wave field including small-amplitude waves with a high temporal resolution in a lacustrine environment. In Lake Constance, wind as well as ship waves contribute to the overall wave field, whereas ship waves are as important as wind waves on an annual scale and even dominate the wave field during summer. The specific occurrence and properties of wind and ship waves cause different temporal patterns and have various implications on sediment resuspension and the underwater light climate, which in turn affect biotic processes in the littoral ecosystem.The results of this thesis demonstrate the strong linkages between physical processes and biological conditions, which supports the need of integrated research

    In-Situ Optical and Acoustical Measurements of the Buoyant Cyanobacterium P. Rubescens : Spatial and Temporal Distribution Patterns

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    Optical (fluorescence) and acoustic in-situ techniques were tested in their ability to measure the spatial and temporal distribution of plankton in freshwater ecosystems with special emphasis on the harmful and buoyant cyanobacterium P. rubescens . Fluorescence was measured with the multi-spectral FluoroProbe (Moldaenke FluoroProbe, MFP) and a Seapoint Chlorophyll Fluorometer (SCF). In-situ measurements of the acoustic backscatter strength (ABS) were conducted with three different acoustic devices covering multiple acoustic frequencies (614 kHz ADCP, 2 MHz ADP, and 6 MHz ADV). The MFP provides a fast and reliable technique to measure fluorescence at different wavelengths in situ , which allows discriminating between P. rubescens and other phytoplankton species. All three acoustic devices are sensitive to P. rubescens even if other scatterers, e.g., zooplankton or suspended sediment, are present in the water column, because P. rubescens containing gas vesicles has a strong density difference and hence acoustic contrast to the ambient water and other scatterers. After calibration, the combination of optical and acoustical measurements not only allows qualitative and quantitative observation of P. rubescens , but also distinction between P. rubescens , other phytoplankton, and zooplankton. As the measuring devices can sample in situ at high rates they enable assessment of plankton distributions at high temporal (minutes) and spatial (decimeters) resolution or covering large temporal (seasonal) and spatial (basin scale) scales
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