What an Insect Brain Can Tell Us: The Impact of Intrinsic and Extrinsic Factors on Long-Term Memory in Drosophila melanogaster Larvae
by Hanna Rebekka Franz
Date of Examination:2024-06-13
Date of issue:2025-01-10
Advisor:Dr. Annekathrin Widmann
Referee:Dr. Annekathrin Widmann
Referee:Prof. Dr. Ernst A. Wimmer
Persistent Address:
http://dx.doi.org/10.53846/goediss-10967
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Abstract
English
Learned associations can be consolidated into long-lasting memory traces, influenced by the relevance and abundance of information, as well as internal states of the animal. In adult Drosophila two distinct forms of consolidated memory have been identified: anesthesia resistant memory (ARM) and long-term memory (LTM). The formation of both memory forms relies on different structural and molecular mechanisms, with LTM exhibiting slower consolidation, higher energy expenditure, and increased persistence compared to ARM. While recent studies have shown that Drosophila larvae are endowed with the ability to form both consolidated memory forms, little is known about the factors determining the formation of a larval LTM. To address this gap, tailored aversive olfactory associative conditioning protocols were utilized to investigate the influence of external and genetic variables on ARM and LTM of Drosophila larvae. Thereby, the presence of a larval LTM was confirmed and its retention over several hours following aversive olfactory spaced conditioning was demonstrated for the first time. To analyze the effect of a decreased energetic state, a method for enduring starvation was developed, revealing that food restriction primarily affects the formation of larval LTM. Furthermore, the newly established starvation technique unveiled a previously unreported LTM impairment in an eye-color mutant widely used as a genetic background strain. Drosophila is endowed with a sophisticated brain compartment known as the mushroom body, which integrates sensory stimuli to drive olfactory associative learning and memory. Investigating whether the function of extracellular signal-related kinase (Erk) and Akt kinase within the mushroom body is implicated in larval memory formation was the central question of a second project. These kinases have been shown to influence memory formation in mammalian species, and evidence exists for an involvement of Erk in LTM formation of adult Drosophila. Furthermore, Erk and Akt are components of the insulin signaling cascade, rendering them intriguing candidates for linking an animal's energy level with the gating process between memory forms, which differ in their energetic requirements. By downregulating Erk and Akt expression within the mushroom body evidence was provided for their specific implication in larval LTM formation. The performance of immunohistochemical stainings verified the presence of activated forms of both kinases within the mushroom body. In one side project, a broader insight is provided into the utility of the Drosophila larva for neuroscientific research. By performing associative olfactory conditioning, deteriorative effects of exposure to the neonicotinoid insecticide imidacloprid on adult memory were found, with the severity of the memory impairment depending on whether the insecticide was applied during larval or adult stages. Moreover, structural and functional alterations in olfactory signal transmission were detected through the monitoring of synaptic connections between specific neuronal populations and the in vivo analysis of fluorescent acetylcholine sensor activity. In summary, this thesis applied multifaceted approaches to study Drosophila memory with a focus on its larval stage, aiming to pave its way to become a popular model not only for learning but also for memory formation.
Keywords: Drosophila melanogaster; Associative conditioning; Long-term memory; Larva; Learning and memory; Mushroom body; Olfaction; Erk; Akt; White mutant; Imidacloprid
