From spatiotemporal restriction of imprecise synaptic partner choice to a robust representation of navigational information in the fly brain

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Closely related neuronal subtypes neighboring each other in the adult brain often exhibit highly specific, divergent connectivity. Modality-specific photoreceptor neurons and their synaptic partners in the Drosophila visual system represent an instance of this phenomenon: While the main portion of the eye and underlying optic neuropils process motion- and color-specific visual input, the dorsal rim area (DRA) processes skylight polarization, ultimately leading to a representation of navigational information in the central brain that is robust over a variety of stimulus conditions. P3 is motivated by our recent team effort of RobustCircuit PIs which discovered that color-sensitive R7 neurons readily form synaptic connections with incorrect partners upon contact, ensuring synaptic specificity in the developing wild type brain by separated synaptogenic interactions in time and space. In P3, we therefore directly compare the selective targeting of DRA photoreceptors R7 and R8 to their specific downstream neurons which process skylight cues, to their color-sensitive counterparts. Based on our preliminary data on neurons in the DRA region, we hypothesize that the robust representation of information processed by DRA neurons are based on their ability to form synapses promiscuously through the differential regulation of synaptogenic encounters in space and time. P3 is devised to test this hypothesis using three complementary approaches: (i) the quantitative investigation of filopodial dynamics of both pre- and postsynaptic cell types via multi-photon ex vivo imaging; (ii) the quantification of variability of neuronal morphology and synaptic distribution by EM-based connectomics; (iii) the quantification of variability and imprecision for creating robust cellular responses, both on a single cell-, as well as on a bulk level, using optophysiology (calcium imaging). Both (i) and (iii) will include wild type brains, as well as targeted manipulations to disrupt filipodial dynamics and neuronal encounters. We will then expand these studies towards neurons that connect the optic lobes with the central brain leading to a robust topographic representation of skylight information there. When these studies are concluded, we will have established a complete 4-dimensional description of the mechanisms for the development of a robust representation of navigational information based on stochastic dynamics in an intact brain.