Abstract
Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement.
Highlights
Neurons communicate through synapses, necessitating a system of checks and balances to achieve precise patterns of synaptic connectivity that execute neural circuit function
We identify pathways that regulate the formation and maintenance of synapses, the functional connections between neurons, in the nervous system of the nematode C. elegans
We address the role of a protein kinase gene TTBK-3 in maintaining synapse structure once synaptic components have reached the sites of new synapses
Summary
Neurons communicate through synapses, necessitating a system of checks and balances to achieve precise patterns of synaptic connectivity that execute neural circuit function. Large scale axonal growth and pruning mediate synapse formation with appropriate targets during development, shaping neuronal circuits during critical periods of plasticity [1]. The mechanisms underlying synapse assembly and elimination have been the subject of intense study for several decades, a majority of experimental models focused on synaptic plasticity that is coupled to neurite outgrowth and retraction [6, 7]. With recent advances in in vivo imaging techniques, instances of synaptic rewiring that are independent of large scale neurite rearrangement have been identified in the mammalian central nervous system [4, 8]. Elucidating the mechanisms underlying the cellular dynamics of such refinement, in pre-synaptic terminals, is of general significance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
