Project Details
Projekt
Harnessing promiscuous synaptogenic potential during the assembly of visual navigation circuitry
Applicant
Professor Dr. Mathias Wernet
Subject Area
Developmental Neurobiology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 453877723
The computation of distinct visual stimuli relies on synaptic connections between related, but distinct sets of specific partner neurons, thereby offering an opportunity to study the robustness of correct synaptic partner choices amongst closely related neurons. In P3, we use the functionally specialized ‘dorsal rim area’ (DRA) of the Drosophila visual system as a model for understanding the assembly of modality-specific circuits for processing one specific navigational cue (skylight polarization), while avoiding nearby color-sensitive inputs. In the previous funding period, our work had two foci: first, the developmental characterization of photoreceptors and their downstream interneurons; second, the characterization of stereotypy and variability in the outcome using connectomics. Our developmental studies largely confirmed the working hypothesis, that spatiotemporal separation of incorrect synaptic partners, while promoting the probabilistic dynamic interactions of correct partners, harnesses the inherently promiscuous synaptogenic potential of photoreceptor neurons. Collaborations within RobustCircuit allowed us to quantitatively model the underlying spatiotemporal cellular interactions and compare them to outcome analyses in the connectome. Similar to other RobustCircuit projects, we found evidence that spatiotemporal dynamics, synaptic competency and selective molecular adhesion contribute to the assembly of the modality-specific circuit. In the second funding period, we want to build on this evidence and quantitatively study the roles of interaction dynamics, synaptic competency and selective adhesion for the development of unidirectional connections downstream of the photoreceptors and their first interneurons in the medulla and the central brain. We hypothesize that unidirectional connectivity harnesses inherently promiscuous synapse formation by three mechanisms: (1) dynamic layer separation of cell types, (2) targeted localization of factors that enable synaptic competency, and (3) selective adhesion, filopodia stabilization and synaptotropic growth. The existence of closely related neuron types processing skylight polarization versus color will allow for a direct comparison between their developmental decisions. We will continue to use a combination of ex vivo live imaging, connectomic analysis, and targeted genetic perturbation to test this hypothesis. In preparation for a second funding period, we have further generated single cell transcriptomes and have established the necessary optophysiological techniques for testing the functional consequences. When these experiments are concluded, we will have characterized the probabilisitc basis for the robustness of developmental choices amongst closely related, but functionally distinct visual circuits.
DFG Programme
Research Units
