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Synaptic plasticity is important for learning and memory formation and describes the strengthening or weakening of connections between synapses. The postsynaptic part of excitatory synapses resides in dendritic spines, which are small protrusions from the dendrites. One of the key features of synaptic plasticity is that it is correlated with the size of these spines. A long-lasting synaptic strength increase (long-term potentiation, LTP) is only possible through the reconfiguration of the actin spine cytoskeleton. Here, we developed an experimentally-informed three-dimensional computational model in a moving boundary framework, which describes the reactions between actin, and actin-binding proteins (ABPs) leading to the cytoskeleton recon-figuration, and their effect in the spine membrane shape, to examine the spine enlargement upon LTP. Our model predicts that spine enlargement during LTP is viscoelastic in nature. We found that volume increase in the spine was more efficient if the stimulus-triggered influx of actin and ABPs were spatially compartmentalized. In response to repeated stimuli, our model predicts that spine growth can be self-regulated by tuning the viscoelastic properties. Thus, we conclude that variation of the viscoelastic properties under different conditions hints at a mechanical regulation of spine expansion during LTP.1Significance StatementDendritic spines are small bulbous protrusions that receive stimulation from presynaptic neurons. Upon stimulation, the dendritic spines change their size, a feature which is hindered during disease. The change in spine size during stimulation is achieved by changes to the actin cytoskeleton and mediated by many actin-binding proteins. To investigate the fundamental mechanics of spine expansion, we developed a minimal 3D model that accounts for the dynamics of cytoskeleton-membrane interactions involved in spine shape changes. Our simulations predict that spine expansion due to actin remodeling can be captured using simple viscoelastic relationships. Additionally, we also found that these mechanical properties can change under different stimuli, allowing for mechanical tuning of spine growth. Thus, we find that spine growth is regulated by the mechanical properties of the spine. |
