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Search Results: 1 - 10 of 298027 matches for " Jürgen Sandkühler "
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Understanding LTP in pain pathways
Jürgen Sandkühler
Molecular Pain , 2007, DOI: 10.1186/1744-8069-3-9
Abstract: Long-term potentiation (LTP) is a much studied cellular model of synaptic plasticity. It is generally defined as the long-lasting but not necessarily irreversible increase in synaptic strength [1,2]. At least two different stages of LTP can be distinguished depending upon its duration and the signal transduction pathways involved. Early phase LTP is independent of de-novo protein synthesis and lasts for up to three hours. Late phase LTP involves protein synthesis and lasts longer than three hours, up to the life span of an animal and may involve structural changes at synapses [3]. Short-term potentiation of synaptic strength lasts less than half an hour. Synaptic strength is the magnitude of the post-synaptic response (i.e. the post-synaptic potential or the post-synaptic current, but not action potential firing, see below) in response to a pre-synaptic action potential. LTP can be expressed pre- and/or postsynaptically, i.e. synaptic strength can increase if the release of neurotransmitter(s) is enhanced and/or if the postsynaptic effects of the neurotransmitter(s) become stronger [4]. LTP at synapses in hippocampus is the prime model for learning and memory formation [1]. Recent studies have shown that LTP can also be induced in pain pathways and may contribute to hyperalgesia caused by inflammation, trauma or neuropathy. This review deals with the latter form of LTP."Central sensitisation" is used in the literature in at least two mutually exclusive definitions. Some of the authors use "central sensitisation" as an umbrella term for all forms of changes within the central nervous system which ultimately lead to enhanced pain perception. If using this definition of "central sensitisation" one should keep in mind that none of the presently known phenomena in the central nervous system (CNS) which can be observed in experimental or clinical models of hyperalgesia or allodynia has a proven, causative role for the perception of pain. Thus, all presently proposed mecha
Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo
Ruth Drdla, Jürgen Sandkühler
Molecular Pain , 2008, DOI: 10.1186/1744-8069-4-18
Abstract: LTP at the first synapse in pain pathways is considered to underlie some forms of pain amplification e.g. after trauma, inflammation or nerve injury [1]. A strong rise in postsynaptic calcium ion concentration triggering Ca2+-dependent signal transduction pathways is required for LTP induction [2-4]. Consequently, high-frequency (~100 Hz), burst-like stimulation protocols were previously used to induce LTP at virtually all synapses studied so far.Low-level activity between 1–10 imp·s-1 rather than high frequency bursts are, however, typical for C-fibre discharges during inflammation, trauma or wound healing. Presynaptic activity at these low frequencies is considered inadequate to cause a sufficiently strong rise in postsynaptic [Ca2+]i for potentiation of synaptic strength. In fact, low-level presynaptic activity was either ineffective or induced synaptic long-term depression (LTD) rather than LTP in previous studies.We have recently discovered that in a spinal cord slice preparation with long dorsal roots intact LFS of dorsal roots at C-fibre intensity induces LTP which involves a rise in postsynaptic [Ca2+]i and Ca2+-dependent signal transduction pathways [4]. In the intact animal spinal dorsal neurons are, however, under a powerful tonic inhibition arising from supraspinal, descending pathways [5,6]. This inhibition is inevitably lost in the in vitro situation and could thereby facilitate LTP-induction. And indeed, removal of descending, putatively inhibitory pathways by spinalisation is required for the induction of LTP by either pinching or noxious heating of the skin [7]. On the other hand, we have shown recently that in the intact animal, LTP can be induced by LFS as well as by subcutaneous capsaicin or formalin injections also [4]. Here, we further characterised this novel LFS-induced LTP at C-fibre synapses in the intact animal.After obtaining approval from the Institutional Animal Care Comitee (Austrian Federal Ministry for Education, Science and Culture)
Effects of peripheral inflammation on the blood-spinal cord barrier
Dimitris N Xanthos, Isabella Püngel, Gabriele Wunderbaldinger, Jürgen Sandkühler
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-44
Abstract: After peripheral carrageenan inflammation, but not capsaicin inflammation, immunohistochemistry shows occludin protein in lumbar spinal cord to be significantly altered at 72?hours post-injection. In addition, there is also significant immunoglobulin G detected in lumbar and thoracic spinal cord at this timepoint in both male and female rats. However, acute administration of sodium fluorescein or Evans Blue dyes is not detected in the parenchyma at this timepoint.Our results show that carrageenan inflammation induces changes in tight junction protein and immunoglobulin G accumulation, but these may not be indicative of a blood-spinal cord barrier breakdown. These changes appear transiently after peak nociception and may be indicative of reversible pathology that resolves together with inflammation.
Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy
Ruth Ruscheweyh, Oliver Wilder-Smith, Ruth Drdla, Xian-Guo Liu, Jürgen Sandkühler
Molecular Pain , 2011, DOI: 10.1186/1744-8069-7-20
Abstract: Pain arising from impending or actual tissue injury has an important physiological role, protecting the body from injury and promoting healing once injury has occurred. Pain persisting in the absence of ongoing nociceptive input from the periphery, or exceeding the pain normally caused by ongoing nociceptive input, has lost its physiological function and is therefore called maladaptive or dysfunctional [1]. Dysfunctional pain is thought to arise from altered processing of nociceptive information in the central nervous system.One of the symptoms of clinically relevant pain is hyperalgesia, i.e. increased pain perception in response to painful stimuli [1,2]. This implies the presence of a mechanism that amplifies nociceptive excitation somewhere along the central nociceptive system. A synaptic amplifier of nociception has been identified at the synapses between primary afferent C-fibres, many of which are nociceptive, and neurons in the superficial dorsal horn of the spinal cord in rodents [3,4]. Amplification of nociceptive signals at this site can be "switched on" by noxious stimulation ("conditioning stimulation") of the associated nociceptive primary afferents. The underlying cellular mechanism is long-term potentiation (LTP) of synaptic strength, a mechanism also described in cortical regions like the hippocampus where it is thought to be the basis of memory formation [5].Therefore, LTP at the first nociceptive synapse is currently regarded as a cellular model of hyperalgesia induced by noxious stimulation. As general anaesthesia without additional analgesia is not sufficient to protect the spinal cord from intraoperative noxious input [6,7], LTP in spinal nociceptive pathways may heighten acute postoperative pain. Moreover, in many patients with chronic dysfunctional pain, pain started to develop following an initial strong noxious input. Examples are chronic postoperative pain following intraoperative noxious input, chronic back pain developing from acute lumba
Central nervous system mast cells in peripheral inflammatory nociception
Dimitris N Xanthos, Simon Gaderer, Ruth Drdla, Erin Nuro, Anastasia Abramova, Wilfried Ellmeier, Jürgen Sandkühler
Molecular Pain , 2011, DOI: 10.1186/1744-8069-7-42
Abstract: Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia.The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.Mast cells are primarily known for their role in Immunoglobulin E (IgE)-dependent hypersensitivity reactions, although their role in a wide range of physiological functions including neuroimmune interactions has been increasingly appreciated [1]. Activation of mast cells usually results in their degranulation, releasing preformed mediators, most notably histamine and chemokines while longer lasting activation results in the release of newly formed mediators such as cytokines, prostaglandins, and leukotrienes [2]. Mast cells are often found in proximity to sensory nerve endings and vasculature and their degranulation can modulate the excitability of nociceptive nerve endings [3]. They can themselves be activated by neurogenically-generated mediators such as substance P [4], various antigens, and inflammatory mediators released in pathophysiological states [5].Peripheral mast cell activation is generally considered pro-inflammatory and pro-nociceptive
Impaired Excitatory Drive to Spinal Gabaergic Neurons of Neuropathic Mice
J?rg Leitner, S?ren Westerholz, Bernhard Heinke, Liesbeth Forsthuber, Gabriele Wunderbaldinger, Tino J?ger, Doris Gruber-Schoffnegger, Katharina Braun, Jürgen Sandkühler
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073370
Abstract: Adequate pain sensitivity requires a delicate balance between excitation and inhibition in the dorsal horn of the spinal cord. This balance is severely impaired in neuropathy leading to enhanced pain sensations (hyperalgesia). The underlying mechanisms remain elusive. Here we explored the hypothesis that the excitatory drive to spinal GABAergic neurons might be impaired in neuropathic animals. Transgenic adult mice expressing EGFP under the promoter for GAD67 underwent either chronic constriction injury of the sciatic nerve or sham surgery. In transverse slices from lumbar spinal cord we performed whole-cell patch-clamp recordings from identified GABAergic neurons in lamina II. In neuropathic animals rates of mEPSC were reduced indicating diminished global excitatory input. This downregulation of excitatory drive required a rise in postsynaptic Ca2+. Neither the density and morphology of dendritic spines on GABAergic neurons nor the number of excitatory synapses contacting GABAergic neurons were affected by neuropathy. In contrast, paired-pulse ratio of Aδ- or C-fiber-evoked monosynaptic EPSCs following dorsal root stimulation was increased in neuropathic animals suggesting reduced neurotransmitter release from primary afferents. Our data indicate that peripheral neuropathy triggers Ca2+-dependent signaling pathways in spinal GABAergic neurons. This leads to a global downregulation of the excitatory drive to GABAergic neurons. The downregulation involves a presynaptic mechanism and also applies to the excitation of GABAergic neurons by presumably nociceptive Aδ- and C-fibers. This then leads to an inadequately low recruitment of inhibitory interneurons during nociception. We suggest that this previously unrecognized mechanism of impaired spinal inhibition contributes to hyperalgesia in neuropathy.
The bulge in the basal plane area of cuprate superconductors - evidence for 3a singlet hole pairs
Jürgen R?hler
Physics , 2006, DOI: 10.1016/j.physc.2007.03.054
Abstract: The bulge in the doping dependence of the basal plane area in hole doped cuprate superconductors is connected with a non-double-occupancy constraint for the oxygen cages in the CuO_2 lattice. This constraint favors the formation of 3a hole pairs growing to filaments with gapless excitations along the (pi, pi) direction. Thus in the pseudogap regime a nodal metal of hole pairs is created. Densest packed 3a hole pairs stabilize the optimum doped state at n =1/6 ~ 0.16.
Nonlinear Doping of Cuprate Superconductors -- The case of Bi_2Sr_{2-x}La_xCuO_{6+δ}
Jürgen R?hler
Physics , 2009, DOI: 10.1016/j.physc.2009.11.027
Abstract: We analyze the hole doping mechanism in Bi_2Sr_{2-x}La_xCuO_{6+\delta} (BSLCO). The singular optimum around x=0.35 is found to be connected with a feedback between the doped CuO_2 layers and its dopant reactant [La^{3+}/Bi^{3+}-O_\delta] locking the number of doped holes preferentially on to the universal optimum n_opt=0.16.
A Reverse Approach to Superconductivity  [PDF]
Shuiquan Deng, Claudia Felser, Jürgen K?hler
Journal of Modern Physics (JMP) , 2013, DOI: 10.4236/jmp.2013.46A003

In contrast to the normal operator approach, our reverse approach starts from the state vector in the Hilbert space. In this work, we give a concise introduction to our recent work in this aspect. By postulating a superconducting state (SCS) to be a generalized coherent state (GCS) constructed by pure group theory, we show that some important properties such as the Cooper pairs of the SCS naturally appear in this new framework without resorting to the microscopic origin. This latter characteristic renders this theory a more universal feature in comparison with other theories developed by the operator approach. The studies on the residue of the pair-wise constraint due to the collapse of the GCS lead to a “flat/steep” band model for searching new superconductors.

Deconstructing Insight: EEG Correlates of Insightful Problem Solving
Simone Sandkühler, Joydeep Bhattacharya
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001459
Abstract: Background Cognitive insight phenomenon lies at the core of numerous discoveries. Behavioral research indicates four salient features of insightful problem solving: (i) mental impasse, followed by (ii) restructuring of the problem representation, which leads to (iii) a deeper understanding of the problem, and finally culminates in (iv) an “Aha!” feeling of suddenness and obviousness of the solution. However, until now no efforts have been made to investigate the neural mechanisms of these constituent features of insight in a unified framework. Methodology/Principal Findings In an electroencephalographic study using verbal remote associate problems, we identified neural correlates of these four features of insightful problem solving. Hints were provided for unsolved problems or after mental impasse. Subjective ratings of the restructuring process and the feeling of suddenness were obtained on trial-by-trial basis. A negative correlation was found between these two ratings indicating that sudden insightful solutions, where restructuring is a key feature, involve automatic, subconscious recombination of information. Electroencephalogram signals were analyzed in the space×time×frequency domain with a nonparametric cluster randomization test. First, we found strong gamma band responses at parieto-occipital regions which we interpreted as (i) an adjustment of selective attention (leading to a mental impasse or to a correct solution depending on the gamma band power level) and (ii) encoding and retrieval processes for the emergence of spontaneous new solutions. Secondly, we observed an increased upper alpha band response in right temporal regions (suggesting active suppression of weakly activated solution relevant information) for initially unsuccessful trials that after hint presentation led to a correct solution. Finally, for trials with high restructuring, decreased alpha power (suggesting greater cortical excitation) was observed in right prefrontal area. Conclusions/Significance Our results provide a first account of cognitive insight by dissociating its constituent components and potential neural correlates.
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