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Title: Molecular and neural mechanisms of olfactory decision making in Drosophila melanogaster
Author: Ferreira, Clara Howcroft
ISNI:       0000 0004 5346 3164
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Traditional studies of simple perceptual choice tasks in vertebrates identified behavioural characteristics of deliberate decision-making that guided the development of general mathematical models, and the search for neurophysiological correlates. Current experimental and modelling efforts aim to uncover biophysical and circuit level mechanisms of decision-making processes. However, genetic manipulability constraints and lack of high-throughput assays make further progress in vertebrate studies a steep endeavour. In this thesis I studied decision-making in Drosophila melanogaster in trained two-alternative forced-choice olfactory tasks with varying stimulus contrast, using a high-resolution single fly behavioural assay. Analysing accuracy and reaction time as a function of task difficulty (i.e., stimulus contrast) showed that flies display behavioural characteristics of evidence accumulation processes, a signature of vertebrate decision-making: reaction times increased and perceptual accuracy declined as stimulus contrast decreased. Mutants for the gene encoding the transcription factor FoxP took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult tasks. Using the putative FoxP promoter to ascertain FoxP expression identified subsets of mushroom body intrinsic Kenyon cells, in αβ core and γ neurons, as potential sites of FoxP action. Disrupting FoxP expression or decreasing neuronal excitability specifically in αβ core neurons mimicked the phenotype observed in FoxP mutants. FoxP expression therefore affects the development or function of αβ core neurons in the progression of a decision process towards commitment. To identify molecular processes involved in evidence integration regulated by FoxP I further screened 2nd and 3rd chromosome deficiency lines in a sensitised FoxP mutant background, uncovering genomic regions of interest for further study. Finally, analysing naive performance in tasks of increasing difficulty showed that naive discriminations are faster and less accurate than trained ones, pointing to the existence of two decision-making systems. FoxP mutants appear to engage the slower, more accurate decision making system and the mushroom body seems to be involved in naive discriminations. The molecular and neuronal players involved in olfactory decision making in Drosophila melanogaster uncovered in this thesis will allow researching decision making systems to an unprecedented level of detail.
Supervisor: Miesenbö ck, Gero Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Physiology and anatomy ; Neuroscience ; Neurogenetics ; Decision-making ; olfaction ; Drosophila melanogaster