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Wiring Specificity Through Imprecise Partner Choice A comparative analysis of visual neurons with highly divergent selectivity profiles

Subject Area Developmental Neurobiology
Term since 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 453877723
 
The series of developmental events leading to wiring specificity in the outcome can be subdivided into the moment when two neurons form a synapse and the developmental periods before and after this 'moment of choice'. Prior to synapse formation, neuronal morphogenesis and the precise localization of axons and dendrites restrict availability of synaptic partners, which significantly influences wiring specificity in the outcome. At the actual moment of choice, a neuron may have the capacity to form a synapse promiscuously or more selectively based on constraints that may include selective adhesion, molecular competency to form a synapse, and the kinetics of interaction. To what extent different neurons are selective or promiscuous at the moment of choice in the context of normal brain development is unknown for most neuron types. In the previous funding period, we studied the development of a single neuron type, dorsal cluster neurons (DCNs), before and up to the moment of synaptic partner choice. The most recent connectomics analysis shows that medulla-innervating DCNs are presynaptic to 186 different neuron types, suggesting non-selectivity. In contrast, photoreceptor neurons 1-6 (R1-6) are on the other end of the spectrum with few postsynaptic partners and high wiring specificity. How different or similar are the moments of choice for the presynaptic axons of these two neuron types? In the first aim of this proposal, we will test the hypothesis that DCNs employ a strategy of imprecise partner choice resulting in synapse formation with a large number of available partners. In the second aim, we propose to apply the same theoretical and experimental framework to R1-6. Our previous work has revealed that R1-6 presynaptic terminals are developmentally sorted together with specific partner neurons prior to synapse formation, which could in principle allow for intrinsically imprecise partner choice, similar to DCNs, and yet result in highly specific R1-6 synaptic connectivity with available partners. When this work is concluded, we will have quantitatively tested the mechanistic similarities of how two very different neuron types with highly divergent specificity profiles in the adult outcome select their partners at the moment of choice.
DFG Programme Research Units
International Connection France
 
 

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