Perception and memories in the fly brain

Abstract

The brain is an extremely complex organ that controls thoughts, memories, motor skills and every process that is required to maintain our body alive and healthy. Although this is common knowledge, the mechanisms by which the brain performs these tasks are currently not fully understood. <br /> In this thesis, I focused on how sensory information is represented in higher brain regions, and how these representations are used to create and consolidate memories related to them. Precisely, using <i>Drosophila melanogaster</i> as a model, I investigated the circuitry of the mushroom body calyx, the input region of a neuropil involved in stimuli discrimination and memory formation in the fly brain. In the calyx, olfactory projection neurons synapse onto mushroom body intrinsic cells, the Kenyon cells, via synaptic complexes known as microglomeruli. Each microglomerulus is a microcircuit of his own, constituted by a central projection neuron presynaptic bouton surrounded by several dendritic endings of different Kenyon cells. This structural organization is believed to facilitate stimuli discrimination by transforming highly overlapping representations at the level of the projection neurons into sparse, decorrelated responses at the Kenyon cells one. Moreover, structural changes at the microglomerular level following associative memory formation have been reported in insect brains over the years. Nevertheless, the exact processes underlying such phenomena have not been described yet. <br /> Here, I show that memory consolidation induces structural plasticity in a stimulus-specific way in the calyx. Specifically, I found that the microglomeruli involved in the representation of the stimulus presented in the behavioural task increased in number after long-term memory formation. This increase in microglomeruli was protein synthesis dependent and strictly linked to the consolidation of the memory, as control flies and mutants unable to consolidate memories did not show structural changes within the same time frame. <br /> Furthermore, in this thesis I analyse the role of inhibitory synapses in microglomeruli of the calyx. Inhibition at the mushroom bodies is provided by the APL neuron, whose presence is required to maintain Kenyon cells odour responses sparse, hence facilitating odours discrimination in the fly. Here, I show that via inhibitory and reciprocal synapses targeting both projection neurons boutons and Kenyon cells dendrites, APL normalizes odour-evoked representations in microglomeruli of the calyx. In particular, I observed that APL inhibition scaled with the inputs strength and localized to the regions where those inputs were located within the calyx, leading to more homogenous responses in Kenyon cells dendrites. I confirmed this hypothesis by inhibiting output from the APL, which led to more variable activities in Kenyon cells dendrites. <br /> Altoghether, this thesis provides insights on how stimuli are processed, represented and used to create associative memories in the fly brain. As similar network organizations can be found in brains of other species including humans, I believe that the principles here described can be potentially applied to all brain regions sharing conformational features with the <i>Drosophila</i> mushroom body.