RobustCircuit Project 6

Project 6 focuses on the role of inherently imprecise synaptotropic dendrite growth and variable ionic current complements of an ensemble of wing depressor motoneurons, which robustly generates stereotypically patterned network output and robust flight motor behavior.

Imprecision: Neuronal development leads to morphologically and functionally noisy differentiation of a set of five interconnected motoneurons which comprise the central pattern generator for flight motor output.

Robustness: Flight is an essential motor behavior that relies on highly robust neural circuit output under changing conditions.

Hypothesis: Developmentally noisy establishment of synaptic connectivity, dendritic structure, and ionic currents benefit the robustness of robust adult circuit function and flight behavior.

Project Summary

Asynchronous insect flight is a prime example for robust motor pattern generation under variable conditions. In Drosophila, the motoneuron activation sequences required for robust yet adjustable wing power production are produced by a small central pattern generating (CPG) network that is comprised of five electrically coupled motoneurons, MN1-5. P6 is motivated by two recent discoveries that raise questions about the development of this system: First, correct CPG output requires balanced synaptic input to MN1-5. We previously showed that correctly balanced excitatory and inhibitory input to a single MN dendrite develops from probabilistic competition, but it remains unknown how the correct synaptic input balance across the MN1-5 ensemble develops. Second, our preliminary data for RobustCircuit show that CPG function requires differential electrical coupling weights between MN1-5 pairs and equally tuned membrane excitabilities of all five MNs, although ion channel expression is considerably variable.  How these imprecisions affect robustness of CPG development and function is unknown. Regarding the first open question, we hypothesize that MN1-5 acquire equal proportions of excitatory synaptic input through synaptotropic growth and competition, both of which are based on intrinsically noisy branching and synapse formation. Regarding the second open question, we hypothesize that imprecise ion channel regulation aids the robust tuning of MN excitability. Moreover, in collaboration with P7, we propose that the mature CPG requires firing pattern imprecision to re-establish preferred MN firing sequences upon perturbation.  When these studies are concluded, we will have characterized how intrinsically imprecise development and neuronal properties lead to stereotyped circuit output and robust behavior.

References

1. Krick N, Ryglewski S, Pichler A, Bikbaev A, Götz T, Kobler O, Heine M, Thomas U, Duch C. (2021). Separation of presynaptic Ca_v2 and Ca_v1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca²⁺ pump PMCA. Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2106621118.
2. Werner J, Arian J, Bernhardt I, Ryglewski S, Duch C. (2020). Differential localization of voltage-gated potassium channels during Drosophila metamophosis. J Neurogenet. 2020 Mar;34(1):133-150.
3. Heinrich L, Ryglewski S (2020). Different α2δ Accessory Subunits Regulate Distinctly Different Aspects of Calcium Channel Function in the Same Drosophila Neurons. Sci Rep 10(1):13670.
4. Schützler N, Girwert C, Hügli I, Mohana G, Roignant JY, Ryglewski S, Duch C (2019)Tyramine action on motoneuron excitability and adaptable tyramine/octopamine ratios adjust Drosophila locomotion to nutritional state. Proc Natl Acad Sci U S A 116(9):3805-3810.
5. Ryglewski S, Vonhoff F, Scheckel K, Duch C (2017)Intra-neuronal Competition for Synaptic Partners Conserves the Amount of Dendritic Building Material. Neuron 93(3):632-645.
6. Kadas D, Klein A, Krick N, Worrell JW, Ryglewski S, Duch C (2017)Dendritic and Axonal L-Type Calcium Channels Cooperate to Enhance Motoneuron Firing Output during Drosophila Larval Locomotion. J Neurosci 37(45):10971-10982.
7. Ryglewski S, Kadas D, Hutchinson K, Schuetzler N, Vonhoff F, Duch C. (2014). Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior. Proc Natl Acad Sci U S A. 111(50):18049-54.