@article{KollertDombertDoeringetal.2015,
  author    = {Kollert, Sina and Dombert, Benjamin and D{\"o}ring, Frank and Wischmeyer, Erhard},
  title     = {Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {12548},
  doi       = {10.1038/srep12548},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148312},
  year      = {2015},
  abstract  = {In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current component of the standing outward current IK\(_{SO}\). A prominent physiological role of TRESK has been attributed to pain sensation. During inflammation mediators of pain e.g. lysophosphatidic acid (LPA) are released and modulate nociception. We demonstrate co-expression of TRESK and LPA receptors in DRG neurons. Heterologous expression of TRESK and LPA receptors in Xenopus oocytes revealed augmentation of basal K\(^{+}\) currents upon LPA application. In DRG neurons nociception can result from TRPV\(_{1}\) activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV\(_{1}\) and hyperpolarising TRESK currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice displayed increased IK\(_{SO}\) after application of LPA whereas under these conditions IK\(_{SO}\) in neurons from TRESK[ko] mice remained unaltered. Under current-clamp conditions LPA application differentially modulated excitability in these genotypes upon depolarising pulses. Spike frequency was attenuated in TRESK[wt] neurons and, in contrast, augmented in TRESK[ko] neurons. Accordingly, excitation of nociceptive neurons by LPA is balanced by co-activation of TRESK channels. Hence excitation of sensory neurons is strongly controlled by the activity of TRESK channels, which therefore are good candidates for the treatment of pain disorders.},
  language  = {en}
}
@article{KohlGruendlerHuysetal.2015,
  author    = {Kohl, S. and Gruendler, T. O. J. and Huys, D. and Sildatke, E. and Dembek, T. A. and Hellmich, M. and Vorderwulbecke, M. and Timmermann, L. and Ahmari, S. E. and Klosterkoetter, J. and Jessen, F. and Sturm, V. and Visser-Vandewalle, V. and Kuhn, J.},
  title     = {Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder},
  series = {Translational Psychiatry},
  volume    = {5},
  journal   = {Translational Psychiatry},
  number    = {e675},
  doi       = {10.1038/tp.2015.171},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138300},
  year      = {2015},
  abstract  = {Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.},
  language  = {en}
}