Drosophila motor neuron boutons remodel through membrane blebbing coupled with muscle contraction

Wired neurons form new presynaptic boutons in response to increased synaptic activity, however the mechanism(s) by which this occurs remains uncertain. Drosophila motor neurons (MNs) have clearly discernible boutons that display robust structural plasticity, being therefore an ideal system in which to study activity-dependent bouton genesis. Here, we show that in response to depolarization and in resting conditions, MNs form new boutons by membrane blebbing, a pressure-driven mechanism that occurs in 3-D cell migration, but to our knowledge not previously described to occur in neurons. Accordingly, F-actin is decreased in boutons during outgrowth, and non-muscle myosin-II is dynamically recruited to newly formed boutons. Furthermore, muscle contraction plays a mechanical role, which we hypothesize promotes bouton addition by increasing MN confinement. Overall, we identified a mechanism by which established circuits form new boutons allowing their structural expansion and plasticity, using trans-synaptic physical forces as the main driving force. Neuronal remodeling is critical for neuronal function. Here, the authors report that motor neurons use membrane blebbing coupled to muscle contraction as a mechanism for synaptic bouton formation, suggesting that mechanical force plays a key role in neuronal remodeling.