RobustCircuit Project 3

Project 3 focuses on the role of morphological variability and positional strategies of dynamic axon-dendritic interactions to restrict an inherently imprecise capacity to form synapses between functionally specialized partners.

Imprecision: Drosophila photoreceptors exhibit stochastic filopodial exploration behavior and can promiscuously form synapses with wrong partners. At the same time, their post-synaptic partners are morphologically diverse, making it impossible to predict their exact tuning properties at a single cell level.

Robustness:  Photoreceptor subtypes detecting skylight polarization make synaptic connections with three distinct postsynaptic partner neuron types, while avoiding contacts with color-sensitive counterparts. On a neuron population level, skylight polarization is represented with robustness to variable neuronal morphologies and presumably also to difficult stimulus conditions.

Hypothesis: Restricted filopodial interactions in time and space ensure differential synapse formation of closely related color- and polarization-sensitive photoreceptor neurons that need not otherwise specify their partner choices. Heavily overlapping, morphologically diverse cell types ensure a robust distribution of synapses (and therefore skylight information) across the entire neuronal population.

Project Summary

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.

References

1. Kind, E., Kind E, Longden KD, Nern A, Zhao A, Sancer G, Flynn MA, Laughland CW, Gezahegn B, Ludwig HD, Thomson AG, Obrusnik T, Alarcón PG, Dionne H, Bock DD, Rubin GM, Reiser MB, Wernet MF. (2021). Synaptic targets of photoreceptors specialized to detect color and skylight polarization in Drosophila. elife 10:e71858.
2. Sancer, G. and Wernet, M.F. (2021). The development and function of neuronal subtypes processing color and skylight polarization in the optic lobes of Drosophila melanogaster. Arthropod Struct Dev. Mar;61:101012.
3. Mathejczyk, T.F., Wernet, M.F. (2020). Modular assays for the quantitative study of visually guided navigation in both flying and walking flies. J Neurosci Methods. 340:108747.
4. Sancer, G., Kind, E., Uhlhorn, J., Volkmann, J., Hammacher, J., Pham, T., Plazaola-Sasieta, H., Wernet, M.F. (2019) Cellular and synaptic adaptations of neural circuits processing skylight polarization in the fly. J Comp Physiol A doi: 10.1007/s00359-019-01389-3.
5. Mathejczyk, T.F., Wernet, M.F. (2019) Heading choices of flying Drosophila under changing angles of polarized light. Sci Rep 9(1):16773. doi: 10.1038/s41598-019-53330-y.
6. Sancer, G., Kind, E., Plazaola-Sasieta, H., Balke, J., Pham, T., Hasan, A., Münch, L.O., Courgeon, M., Mathejczyk, T.F., Wernet, M.F. (2019) Modality-Specific Circuits for Skylight Orientation in the Fly Visual System. Curr Biol 29(17):2812-2825.e4. doi: 10.1016/j.cub.2019.07.020.