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bioRxiv · 10.1101/2022.11.06.515372

Biophysical modeling of actin-mediated structural plasticity reveals mechanical adaptation in dendritic spines

Bonilla-Quintana, M.·Rangamani, P.
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Abstract

Synaptic plasticity is important for learning and memory formation; it describes the strengthening or weakening of connections between synapses. The postsynaptic part of excitatory synapses resides in dendritic spines, which are small protrusions on the dendrites. One of the key features of synaptic plasticity is its correlation 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 develop an experimentally-informed three-dimensional computational model in a moving boundary framework to investigate this reconfiguration. Our model describes the reactions between actin and actin-binding proteins (ABPs) leading to the cytoskeleton remodeling and their effect on the spine membrane shape to examine the spine enlargement upon LTP. Moreover, we find that the incorporation of perisynaptic elements enhances spine enlargement upon LTP, exhibiting the importance of accounting for these elements when studying structural LTP. Our model shows adaptation to repeated stimuli resulting from the interactions between spine proteins and mechanical forces. Significance StatementDendritic spines are small protrusions that receive stimulation from presynaptic neurons. Upon stimulation, the dendritic spines change their size, an important feature of synaptic plasticity. This change is achieved by modifications to the actin cytoskeleton and mediated by many actin-binding proteins. To investigate the fundamental mechanics of spine expansion, we developed a 3D biophysical model that accounts for the dynamics of cytoskeleton-membrane interactions. Our simulations predict that spine expansion due to actin remodeling can be enhanced by including the interaction with perisynaptic elements that affect the spines mechanical properties. We also found that mechanical properties can control spine expansion after repeated stimuli, which ensures physiological size. Thus, we predict that spine growth is regulated by its mechanical properties.

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Bonilla-Quintana, M., Rangamani, P.. 2022-11-06. Biophysical modeling of actin-mediated structural plasticity reveals mechanical adaptation in dendritic spines. https://doi.org/10.1101/2022.11.06.515372

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