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? The specificity of innumerable synaptic contacts is of central importance to the study of brain development and function. In contrast, terms like 'imprecision' and 'noise' are more commonly used in association with faulty development and reduced function. In most studies of neuronal development and function, imprecision only features as error bars and in the hope for significance between control and experimental averages. Yet, the development of neural circuits is in many aspects imprecise, and mature circuitry is often highly flexible and error-tolerant, i.e. robust. The core hypothesis of RobustCircuit is 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. In the proposed Research Unit, we intend to explore the different types of imprecision most commonly observed in neural circuit assembly and to interrogate their nature, ranging from unavoidable noise to necessary contributors in development and function. Neural circuit assembly must deal with imprecision of different varieties: molecular noise, subcellular random dynamics, variability in axonal and dendritic shape, cellular heterogeneity, the imprecise encoding of a developmental event, e.g. synaptic partner choice, to name but a few. To ensure comparable and integrative insight from these different types of imprecision, we propose to harness the 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 individual neurons can reproducibly be manipulated and their development and activity observed with live imaging of whole brain explants as well as in behaving animals. The goal of RobustCircuit is to understand the roles of developmental imprecisions for robust outcomes by comparing and integrating examples across neuron types and scales from molecules to behavior. Our integrative approach is devised to provide both quantitative comparisons as well as analyses of shared computational models at the end of a first funding period. Our long-term perspective is expansion to other model systems.

• DFG Programme: Research Units
• International Connection: France

Projects

• Comparative Quantitative Image Acquisition, Analysis and Modeling (Applicants Baum, Daniel ;  Hiesinger, Peter Robin ;  Von Kleist, Ph.D., Max )
• Coordination Funds (Applicant Hiesinger, Peter Robin )
• Developmental noise aids robust motor pattern generation and behavior (Applicants Duch, Carsten ;  Ryglewski, Stefanie )
• From imprecise synapse seeding to robust synapse formation by stabilization mechanisms of early molecular scaffolds (Applicants Petzoldt, Astrid G. ;  Sigrist, Stephan J. )
• From spatiotemporal restriction of imprecise synaptic partner choice to a robust representation of navigational information in the fly brain (Applicant Wernet, Mathias )
• Imprecise connectivity of olfactory projection neurons in the lateral horn underlies robust innate behaviors (Applicant Martelli, Ph.D., Carlotta )
• Robust axonal branch patterning through stochastic filopodial dynamics (Applicant Hiesinger, Peter Robin )
• Robust network states from variable ion channel composition and connectivity: a mathematical approach in a Drosophila motocircuit (Applicant Schreiber, Susanne )
• Sex-specific differences in the variability of Dorsal Cluster Neuron branching lead to sexually dimorphic wiring asymmetry and behavior (Applicant Linneweber, Ph.D., Gerit )
• Variability and robustness of functional neuronal properties in visual motion-detection circuitry (Applicant Silies, Marion )

• Spokesperson: Professor Dr. Peter Robin Hiesinger