Establishment of the circuit of the mushroom body calyx during development

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The correct evaluation of sensory information, the definition of an accurate behavioral goal, the coordinated control of movement, all depend upon carefully designed flows of information within the nervous system – guaranteed by the architecture of neuronal networks. During development, neurons migrate to defined target locations and differentiate their complex and neuron-type specific axon and dendrites. Having reached their appropriate target region, they face the major tasks of identifying their correct partners among many and of generating connections in appropriate numbers. With the level of resolution provided by electron microscopy-based reconstructions of neuronal circuits, the complexity of local microcircuit architecture has recently emerged even more clearly. Within the mushroom body (MB) calyx, sensory information is processed to elicit a sparse code of response by the Kenyon cells (KCs). Our ongoing work, funded by the FOR2705, indicates that this fundamental property of the MB (and of many circuits across evolution) relies on the architecture of the main structural unit of the MB calyx, the microglomeruli (MGs). We concentrate on the processing of olfactory information and have described how, within each MG, the axonal bouton of an olfactory projection neuron is surrounded by the dendrites of many KCs to form a spherical structure of highly interconnected elements. With the level of description we produced, MGs seem an ideal system to address how specific connections are formed during development. However, virtually nothing is known about how MGs arise. We propose here to reveal key molecular factors and the fundamental logic of how these complexes assemble by performing a classic genetic screen. Using transcriptomic data, we have defined a set of surface molecules expressed by projection neurons or by KCs as candidates for supporting neuron-neuron recognition in the calyx. We will screen by RNAi- mediated knock-down for conditions in which the MGs, the projection neuron boutons, the KC dendrites or their synaptic contacts are not correctly formed, maintained or positioned. The best molecular candidates will be thoroughly analyzed with a combination of genetics, high-resolution imaging and cell biology techniques. To support these studies and help clarifying how mutant phenotypes emerged, we will investigate with time-lapse imaging the dynamic behavior of individual axons and dendrites during development and address the impact of activity during the process. Finally, in addition to the local microcircuits represented by the MGs, we will address also the logic of the global organization of the MB calyx, by generating a map of sensory representation. We will address how this map emerges and its stereotypy among individuals. Taken together, we will lay the ground of the logic of developmental assembly of a key circuit in the adult fly brain – in the context of the functional properties of the completed circuit.