PT  - JOURNAL ARTICLE
AU  - Andreia R. Fernandes
AU  - César S. Mendes
AU  - Edgar R. Gomes
AU  - Rita O. Teodoro
TI  - Motor neuron boutons remodel through membrane blebbing
AID  - 10.1101/2021.03.07.434250
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.07.434250
4099  - http://biorxiv.org/content/early/2021/03/07/2021.03.07.434250.short
4100  - http://biorxiv.org/content/early/2021/03/07/2021.03.07.434250.full
AB  - Wired neurons form new presynaptic boutons in response to increased synaptic activity, but the mechanism by which this occurs remains uncertain. The neuromuscular junction (NMJ) is a synapse formed between motor neurons (MNs) and skeletal muscle fibers and is critical for control of muscle contraction. Because MNs have clearly discernible boutons and display robust structural plasticity, it is the ideal system in which to study bouton genesis. Here we show using ex-vivo and by live imaging that in response to depolarization, MNs form new boutons by membrane blebbing, a pressure-driven mechanism used in 3-D migration, but never described as a neuronal remodeling strategy. In accordance, F-actin is decreased during bouton growth (a hallmark of blebs) and we show that non-muscle myosin-II (a master regulator of blebbing) is recruited to newly formed boutons. Furthermore, we discovered that muscle contraction plays a mechanical role in activity-dependent plasticity, promoting bouton addition by increasing MNs confinement. Overall, we provide a novel mechanism by which established circuits create new boutons allowing their structural expansion and plasticity, using trans-synaptic physical forces as the main driving force. Understanding MN-muscle interplay during activity-dependent plasticity can help clarify the mechanisms leading to MN degeneracy observed in neuromuscular diseases.Competing Interest StatementThe authors have declared no competing interest.