FOR 5289:  From Imprecision to Robustness in Neural Circuit Assembly

• Subject Area: Medicine ; Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 453877723

Why imprecision and robustness? With this question we introduced our concept-driven research unit for its first funding period, and it remains upfront as we are preparing to harness the continually growing collaborations, conceptual advances and momentum in a second funding period. The relevance of approaches to understand how inherently imprecise processes control the development of both precise and variable brain wiring has become more prominent during the first funding period, partly due to findings, publications and presentations of the RobustCircuit consortium. The core hypothesis of RobustCircuit states that imprecisions of distinct processes at lower scales (from molecules to cells) enable robustness of circuit assembly and function at higher scales (from cells to behavior). While numerous examples support this notion, we are not aware of any concerted effort akin to RobustCircuit, with a focus on the importance of imprecise development for robust neural circuit connectivity and function. For the RobustCircuit team, the collaborative interrogation of a shared concept has transformed approaches and, in some cases, the very thinking about the problems we are studying. On this basis, we plan to continue to explore the different types of imprecisions observed in neural circuit assembly and to interrogate their nature, ranging from unavoidable noise to necessary contributors in development and function. The project proposals for a second funding period build on the successes and lessons of our findings until now. Neural circuit assembly must deal with numerous imprecisions: molecular noise, random subcellular dynamics, cellular (morphological) heterogeneity, the imprecision of developmental events, e.g. synaptic partner choice, to name but a few. To ensure comparable and integrative insight, we have decided to continue to harness our momentum in the study of selected neural circuits in a single model organism, Drosophila melanogaster. In the fly, neural circuit connectivity has been documented in great detail and the newly published connectomes (with the contribution of several RobustCircuit PIs), provide quantitative measures for stereotypy and variability of the developmental outcomes. However, the goal of RobustCircuit is an understanding of fundamental roles of developmental imprecisions for robust outcomes that apply to any species with a brain.

• DFG Programme: Research Units
• International Connection: France

Projects

• Coordination Funds (Applicant Hiesinger, Peter Robin )
• Developmental noise aids robust motor pattern generation and behavior (Applicants Duch, Carsten ;  Ryglewski, Stefanie )
• Harnessing promiscuous synaptogenic potential during the assembly of visual navigation circuitry (Applicant Wernet, Mathias )
• Mechanisms for robust odour coding based on variable circuit architectures (Applicant Martelli, Ph.D., Carlotta )
• Metabolic Regulation of Probabilistic Axon Growth Leads to Robust Sex-Specific Brain Asymmetry and Behavior (Applicant Linneweber, Ph.D., Gerit )
• Origin and function of imprecise connectivity in motion-detection circuits (Applicant Silies, Marion )
• Quantitative Data Analysis and Computational Modelling (Applicants Baum, Daniel ;  von Kleist, Max )
• Robust computational network phenotypes from the heterogeneity of ion channel types, neuronal morphology, and temperature (Applicants Schleimer, Jan-Hendrik ;  Schreiber, Susanne )
• Stochastic early assembly as the molecular basis of robust active zone formation (Applicants Petzoldt, Astrid G. ;  Sigrist, Stephan J. )
• Wiring Specificity Through Imprecise Partner Choice A comparative analysis of visual neurons with highly divergent selectivity profiles (Applicants Hassan, Ph.D., Bassem ;  Hiesinger, Peter Robin )

• Spokesperson: Professor Dr. Peter Robin Hiesinger