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Development and Function of Central Neuron Dendrites

Subject Area Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2016 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 327562957
 
Final Report Year 2022

Final Report Abstract

The main goal of this proposal was to utilize Drosophila as a genetic model organism to study specific aspects of dendritic differentiation in the central nervous system. Based on preliminary data we had hypothesized that Dscam1 is not employed as a nervous system wide code for dendritic self-avoidance in the central nervous system. We confirmed this by showing that Dscam1 is not required for dendrite spacing of all 5 different types of interneurons which we studied in the VNC and in the brain. By contrast, Dscam1 is required for dendrite but not for axonal differentiation in different types of efferent neurons in the VNC. There, Dscam1 is not employed for dendrite spacing only, but instead, takes on neuron type specific functions in arbor growth and branching. We made similar observations for the other 3 Dscam family members, Dscam2-4 (Wilhelm et al., in preparation). Together, these data highlight diverse neuron-type specific functions of all Dscam family members in the Drosophila central nervous system. We consider this an important extension to the common view that probabilistic Dscam1 isoform generation is employed for arbor spacing of all neurons through homophilic repulsion. As an alternative mechanism for dendrite spacing, we studied synaptotropic growth during dendritic differentiation of the identified flight motoneuron, MN5. We found that both GABAergic and cholinergic synaptic inputs cause postsynaptic dendritic branch stabilization in a synaptotropic manner via local dendritic calcium signals. We further found that competition of GABAergic and cholinergic synaptic partners for postsynaptic partner dendrites locally shapes the different dendritic input domains. Ultimately these mechanisms serve the correct allocation of different numbers of excitatory and inhibitory inputs to one postsynaptic target neuron. Mis-regulation causes dendrite shifts between different dendritic input domains, which in turn, impairs fine motor control neuron flight.

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