Transient spine enlargement (3-5 min timescale) is an important event
associated with the structural plasticity of dendritic spines. Many of the
molecular mechanisms associated with transient spine enlargement have been
identified experimentally. Here, we use a systems biology approach to construct
a mathematical model of biochemical signaling and actin-mediated transient
spine expansion in response to calcium-influx due to NMDA receptor activation.
We have identified that a key feature of this signaling network is the
paradoxical signaling loop. Paradoxical components act bifunctionally in
signaling networks and their role is to control both the activation and
inhibition of a desired response function (protein activity or spine volume).
Using ordinary differential equation (ODE)-based modeling, we show that the
dynamics of different regulators of transient spine expansion including CaMKII,
RhoA, and Cdc42 and the spine volume can be described using paradoxical
signaling loops. Our model is able to capture the experimentally observed
dynamics of transient spine volume. Furthermore, we show that actin remodeling
events provide a robustness to spine volume dynamics. We also generate
experimentally testable predictions about the role of different components and
parameters of the network on spine dynamics
