Mechanisms underlying rapid activity-dependent structural plasticity at Drosophila neuromuscular junctions
Author(s)Piccioli, Zachary D. (Zachary David)
Massachusetts Institute of Technology. Department of Biology.
J. Troy Littleton.
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The Drosophila neuromuscular junction (NMJ) is capable of rapidly budding new presynaptic varicosities over the course of minutes in response to elevated neuronal activity. Using live imaging of synaptic growth, we characterized this dynamic process and demonstrate that rapid bouton budding requires retrograde BMP signaling and local alteration in the presynaptic actin cytoskeleton. BMP acts during development to provide competence for rapid synaptic growth by regulating the levels of the Rho GEF trio, a transcriptional output of BMP-Smad signaling. In a parallel pathway, we find that the BMP type 11 receptor Wit signals through the effector protein LIM domain kinasel (Limk) to regulate bouton budding. Limk interfaces with structural plasticity by controlling the activity of the actin depolymerizing protein Cofilin. Expression of constitutively active or inactive Cofilin in motor neurons demonstrates that increased Cofilin activity promotes rapid bouton formation in response to elevated synaptic activity. Correspondingly, overexpression of Limk, which inhibits Cofilin, inhibits bouton budding. Live imaging of the presynaptic F-actin cytoskeleton reveals that activity-dependent bouton addition is accompanied by formation of new F-actin puncta at sites of synaptic growth. Pharmacological disruption of actin turnover inhibits bouton budding, indicating local changes in the actin cytoskeleton at preexisting boutons precede new budding events. We propose that developmental BMP signaling potentiates NMJs for rapid activity-dependent structural plasticity that is achieved by muscle release of retrograde signals that regulate local presynaptic actin cytoskeletal dynamics.
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2014.Cataloged from PDF version of thesis.Includes bibliographical references.
DepartmentMassachusetts Institute of Technology. Department of Biology.; Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology