Die Neurone der medialen Amygdala spielen eine wichtige Rolle bei der Verarbeitung von unkonditionierter Angst und aggressivem Verhalten (Nelson and Trainor, 2007). Ihre Erregbarkeit wird höchstwahrscheinlich durch eine Hintergrundleitfähigkeit von K2P-Kanälen und ihrem molekularen Korrelat reguliert. Bisher sind 15 dieser K2P-Kanäle bekannt. In der hier vorliegenden Arbeit wurden die Expression und die physiologische Funktion des TASK-3, einem säure-sensitivem K2P-Kanal, in dieser Gehirnregion untersucht. Bisher konnte die TASK-3-Expression durch in situ-Hybridisierungen in erwachsenen Ratten gezeigt werden (Karschin et al., 2001). Entsprechend konnten wir einen, dem TASK-3 ähnlichen Strom, durch elektrophysiologische Ganzzellmessungen in akuten Hirnschnitten nachweisen. Um die Beteiligung des TASK-3 an diesem Gesamtstrom zu überprüfen, verwendeten wir den selektiven TASK-3 Antagonisten Ruthenium Rot oder veränderten den extrazellulären pH-Wert auf pH 6,4. Ruthenium-Rot- bzw. pH-sensitive Neurone zeigten ein negativeres Ruhemembranpotential (-56.31 mV ± 1.51; n = 17) als die Neurone, die nicht sensitive für Ruthenium-Rot oder pH-Veränderungen waren (-48.39 mV ± 1.55; n = 13; p = 0.001). Zusätzlich verstärkte Ruthenium Rot die Aktionspotenzialfrequenz und die Aktionspotenzialbreite bei Stromapplikation in den Zellen mit einem positiveren Ruhemembranpotenzial. Unsere in situ-Hybridisierungen in C57/Bl6 Mäusen zeigten eine starke Expression des TASK-3-Kanals in den Neuronen der medialen Amygdala. Darum wurde die Erregbarkeit von TASK-3 Wildtypneuronen mit denen von TASK-3-Knockoutneurone verglichen. Wir konnten einen säuresensitiven Kaliumstrom in den TASK-3 Wildtypzellen identifizieren, welche in den TASK-3 Knockoutzellen abwesend war. Überraschenderweise tauchten keine Unterschiede in der Aktionspotenzialform, dem Ruhemembranpotenzial oder des Rheobasestrom auf. Verhaltenstests zeigten, dass TASK-3 Wildtyp Mäuse auf die Präsentation von TMT, ein Duftstoff aus den Fäkalien von Füchsen, stärker freezen, als TASK-3 Knockoutmäuse. Dies zeigt, dass ein Fehlen des TASK-3 zu einer geringeren Furchtantwort beiträgt. Zusammengefasst zeigen diese Daten, dass TASK-3 bei der zellulären Erregbarkeit von Neuronen der medialen Amygdala von Ratten eine große Rolle spielt. Diese TASK-3-Kanäle sind in der medialen Amygdala von Mäusen ebenso exprimiert, wo sie zur Verarbeitung von Furchtverhalten beitragen. / Neurones of the medial amygdala play an important role in processing unconditioned fear and aggressive behaviour (Nelson and Trainor, 2007). Their excitability is supposed to be regulated by a background conductance with two-pore domain potassium channels (K2P) as its molecular correlate. So far, there are 15 K2P channels known. In this thesis the expression and the physiological function of TASK-3, an acid-sensitive K2P-channel, in this brain region was investigated. Previously, there was a TASK-3 channel expression in the medial amygdala from adult rats demonstrated by in situ-hybridisation (Karschin et al., 2001). Correspondingly, we also detected a TASK-3-like current by electrophysiological whole-cell measurements in acute brain slices. To identify the contribution of TASK-3 to the standing outward current (IKso) upon depolarising pulses we used the selective TASK-3 antagonist ruthenium red (RR) or acidification to pH 6.4. RR- or pH-sensitive neurones showed a more hyperpolarised resting membrane potential (-56.31 mV ± 1.51; n = 17) compared to neurones lacking TASK-3-like currents (-48.39 mV ± 1.55; n = 13; p = 0.001). In addition, Ruthenium Red enhanced action potential frequency and action potential width during current injections in the more hyperpolarised cells. Our in situ-hybridizations in C57/Bl6 mice indicate that the same member of the K2P, acid sensitive TASK-3 channel, is also strongly expressed in neurones of the medial amygdala of mice. We therefore compared medial amygdaloid excitability in TASK-3 wildtype and TASK-3 knockout mice. We could detect an acid sensitive potassium current in the TASK-3 wildtype mice, which was absent in the TASK-3 knockout mice. Surprisingly, we could not detect significant differences in parameters defining the shape of an action potential, the resting membrane potential or the rheobase current. Behavioural tests analyzing the freezing behaviour showed that TASK-3 wildtype mice do react stronger to the frightful odour of TMT than TASK-3 knockout mice. Indicating, that TASK-3 knockout mice do have less fear response. Taken together, these data suggest that TASK-3 channels are very important in controlling cellular excitability of medial amygdaloid neurones in rats. These TASK-3 channels are also expressed in mice where they contribute to the fear behaviour of freezing.

Diss. Stockholm : Stockholms universitet, 2009.

This dissertation is a comparative study which traces the development of a distinctive aesthetics in the late twentieth century novels of the Austrian writer, Christoph Ransmayr. The three novels, Die Schrecken des Eises und der Finsternis, Die letzte Welt and Morbus Kitahara, while quite different in terms of spatial and temporal orientation, share several key features which contribute to the operation of what I define and examine as the aesthetics of humility in the texts. These recurrent thematic, structural and symbolic elements in the three novels relate to the texts??? critique of scientific modernity, their privileging of myth (both thematically and stylistically), the representation of nature and the texts??? readings of apocalypse and transformation. The theory of myth developed by Hans Blumenberg in Arbeit am Mythos provides an interpretative framework to explain the re-emergence of myth as a contemporary response to the ???absolutism of reality??? which the systems and technologies of scientific modernity have produced in the twentieth century. The first part of this thesis examines the representation in individual novels of the collapse and breakdown of selected metanarratives of modernity. The second part consists of an examination of three core myths which function to restructure the narrative of human existence in each novel. This thesis determines that the development of the aesthetics of humility in Ransmayr???s novels is dependent on the reader???s recognition of the changed perspective and the changed perception which characters in each novel experience. To different extents the characters in each novel abandon a rational perception of reality. The aesthetics of reality acknowledges a textual consciousness and privileging of the projected Other of reason; nature, myth, fantasy, irrationality and barbarity. The human subject no longer occupies the privileged central position in humanist cosmology. Displaced from the centre to the periphery of civilization, the human subject is also represented as having lost control of its physical and psychical environment. Human pretensions to power and influence over itself and its environment are negated in the texts??? revelation of the transience of life. This loss of status and place is related on a seemingly moral level to the novels??? representation of the human potential for brutality and cruelty. The ultimate disappearance of the human subject in each novel is related to the subject???s gradual objectification in the text and the final dissolution of its identity.

This dissertation is a comparative study which traces the development of a distinctive aesthetics in the late twentieth century novels of the Austrian writer, Christoph Ransmayr. The three novels, Die Schrecken des Eises und der Finsternis, Die letzte Welt and Morbus Kitahara, while quite different in terms of spatial and temporal orientation, share several key features which contribute to the operation of what I define and examine as the aesthetics of humility in the texts. These recurrent thematic, structural and symbolic elements in the three novels relate to the texts??? critique of scientific modernity, their privileging of myth (both thematically and stylistically), the representation of nature and the texts??? readings of apocalypse and transformation. The theory of myth developed by Hans Blumenberg in Arbeit am Mythos provides an interpretative framework to explain the re-emergence of myth as a contemporary response to the ???absolutism of reality??? which the systems and technologies of scientific modernity have produced in the twentieth century. The first part of this thesis examines the representation in individual novels of the collapse and breakdown of selected metanarratives of modernity. The second part consists of an examination of three core myths which function to restructure the narrative of human existence in each novel. This thesis determines that the development of the aesthetics of humility in Ransmayr???s novels is dependent on the reader???s recognition of the changed perspective and the changed perception which characters in each novel experience. To different extents the characters in each novel abandon a rational perception of reality. The aesthetics of reality acknowledges a textual consciousness and privileging of the projected Other of reason; nature, myth, fantasy, irrationality and barbarity. The human subject no longer occupies the privileged central position in humanist cosmology. Displaced from the centre to the periphery of civilization, the human subject is also represented as having lost control of its physical and psychical environment. Human pretensions to power and influence over itself and its environment are negated in the texts??? revelation of the transience of life. This loss of status and place is related on a seemingly moral level to the novels??? representation of the human potential for brutality and cruelty. The ultimate disappearance of the human subject in each novel is related to the subject???s gradual objectification in the text and the final dissolution of its identity.