Neuronale Grundlagen von Antrieb und Antriebshemmung bei Drosophila melanogaster

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Abstract

It was the aim of this thesis to analyze the control of behavioral activity in response to environmental and internal stimuli in Drosophila melanogaster. An increase in behavioral activity in response to positive stimuli is anthropomorphically called enhanced motivation, whereas repeated or long-lasting stress or failure may lead to a decrease in behavioral activity and in the long run to major depression. The motivational state of a fly can reliably be quantified by its willingness to overcome broad gaps in a narrow catwalk by a complex climbing action. The motivational state of a fly can reliably be quantified by its willingness to overcome broad gaps in a narrow catwalk by a complex climbing action. On the other hand “learned helplessness“, an accepted animal model of major depression diminishes the motivation of flies to climb the gap. Learned helplessness can emerge by repeated stressful events unavoidable to the animal. A robust paradigm to generate learned helplessness in flies has been developed in the current study. Learned helplessness was reliably elicited by repeated, not foreseeable, unavoidable vibrations of 300 Hz and 20s duration during 8h per day and over the course of several days. In comparison to control flies not just the climbing activity of the treated flies was reduced but also their behavioral activity in walking and courtship; the term “depression-like state” seems therefore justified. A model for the regulation of behavioral activity by the mushroom bodies has been developed on basis of the experimental results of this thesis. Vibrational stress is mediated by reduced release of serotonin into the α-lobes of the mushroom bodies, whereas positive events, like sugar intake, are signaled by an overall increased release of this neuromodulator. The γ-lobes act antagonistically to the α-lobes, because artificial activation of the γ-Kenyon cells with their 5-HT1B receptors let the animals become „depressive“ more easily, whereas artificial inactivation of the same γ-Kenyon cells let the flies resist the depression-like state. A natural cause for the modulation of the serotonin release into the γ-lobes has yet to be found. Modulation of activity by attractive olfactory or visual stimuli, however, acts through the α-/β-Lobes, because only there the modulation could be stopped by blocking the chemical synapses.

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