Neural circuit plasticity underlying learning and memory in Drosophila melanogaster: from synaptic connections to behavior
by El Yazid Rachad
Date of Examination:2023-03-17
Date of issue:2023-05-12
Advisor:Prof. Dr. André Fiala
Referee:Prof. Dr. André Fiala
Referee:Prof. Dr. Ralf Heinrich
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Name:Doctoral Thesis - Yazid .pdf
EnglishUnderstanding the principles behind olfactory higher-order associative chains formation in Drosophila is one step further into unraveling the essence of learning and memory. However, the rationale behind such mechanisms sprouts since the development of the young brain to its full potential and its ability form complex and intermingled connections governing this type of higher-order learning. First, we took a developmental approach to assess the activity behind neuronal development of the center of olfactory learning in the fruit fly, the mushroom body (MB). We could demonstrate that pruning and remodelling of the the MB, that are necessary for its healthy development, occur by its hyperpolarisation by cell-autonomous and external factors. The interruption of such processes leads to the poor development of the MB along with its synaptic partners, thus translating to a potential deficit in olfactory memory formation in the adult stage. Then, we worked towards scrutinizing the synaptic plasticity underlying olfactory learning in the context of a classical aversive conditioning paradigm in the second manuscript. We show that association of a conditioned stimulus (i.e. odor) with a punishment (i.e. electric shocks) leads to localized synaptic changes between odor encoding cells (Kenyon cells KCs) and behavioral mediating output neurons (MB output neurons MBONs) in one distinct compartment of the MB, the γ1. In the third and last manuscript, we designated second-order conditioning (SOC) as a higher-order form of learning to unravel and get one step closer to understanding the principles of associative chains in learning. SOC can be achieved when a previously conditioned stimulus (CS1) is paired with a second-conditioned stimulus (CS2), eliciting a conditioned response to the CS2. This type of conditioning offers the opportunity to examine how the internal transfer of information from CS1 to CS2 occurs on cellular and molecular levels. Therefore, investigating the yet unclear neuronal microcircuit that underlies this behavior is of importance. By thermo-genetically manipulating MB neuronal populations, we could show distinct microcircuits that are implicated in this higher-order form of aversive olfactory learning during different phases of training and test in SOC. Then, functional imaging along with connectomics analysis procured a better understanding of the dynamics between the candidate neurons, from which emerges a proposed model for SOC. We suggest that two parallel MB compartments work in synergy allowing a previously conditioned odor through bidirectional feedback loops to hijack the punishment-mediating dopaminergic neurons, and thus formation of higher-order associations.
Keywords: Drosophila, Olfactory learning, Second-order conditioning, Mushroom body, Synaptic plasticity, Pruning.; Drosophila, Olfactotion, Learning and memory, Second-order conditioning, Mushroom body, Synaptic plasticity, Development, Pruning.