Changing expectations : cognitive flexibility and reward processing in larval Drosophila

Abstract

How brains function to generate appropriate behaviours is a key question for neuroscientists. The larva of Drosophila melanogaster is emerging as a powerful study case for investigating the neural circuits underlying behaviour. Critically, the numerical simplicity of the larval nervous system has recently allowed its complete synapse connectome to be reconstructed, revealing unexpected circuit complexity. Examining the functions of the newly discovered circuit motifs through learning tasks more complex than hitherto employed now represents a major step. The present thesis deals with this challenge. In the first part, I establish a reversal learning paradigm, a non-elemental learning task where larvae are trained to reverse their behaviour according to previously learned contingencies. Reversal learning is demonstrated in a surprisingly quick, one-trial contingency adjustment, both in the appetitive and aversive domain, providing a simple and genetically easily accessible study case of cognitive flexibility. In the second part, I study one of the most complex neurons in the larval brain, the GABAergic anterior paired lateral (APL) neuron. Although APL function has been extensively studied in adults, major differences in APL connectivity between larvae and adults may suggest different functions between developmental stages, calling for a detailed look into APL function in larvae. Using a combination of behavioural analysis, optogenetics, pharmacology, and connectomics, I aim to understand how APL modulates associative olfactory memory. I first provide a detailed account of the structure and connectivity of APL. I further reveal that, surprisingly, activating APL optogenetically has a rewarding effect. Specifically, driving APL together with the presentation of an odour can establish an odour-specific, short-term associative memory. Systemic pharmacological inhibition of dopamine signalling impairs this memory, suggesting the involvement of downstream dopaminergic neurons. These findings thus provide a study case of unexpected behavioural and circuit complexity in an animal as seemingly simple as the Drosophila larva.