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Can calcium ion contribute to morphological plasticity of a spine?
BMC Neurosciencevolume 9, Article number: P101 (2008)
Structural plasticity of a spine, which is a change in the spine morphology with synaptic stimulation, has been reported from several labs. Structural plasticity is thought to be a consequence of the induction of long-term potentiation. Some reports suggested the role of actin molecules in the structural plasticity, and the change in F-actin structure will play a pivotal role in the morphological change of a spine [1–4]. The structure of F-actin is controlled by complex mechanisms, and the molecular mechanisms which contribute to morphological plasticity of a spine are not understood yet. Here, we performed several simulations to see whether the intracellular calcium ion can trigger the structural plasticity of a spine. Simulation results have shown calcium could be a molecule triggering the morphological change of a spine. From these simulation results, we propose a hypothetical mechanism involved in the structural plasticity.
Morphological models including mushroom spines and filopodium with different size in head and neck diameter were constructed using A-Cell software [5, 6]. The 3D morphology was compartmentalized, and Ca2+ entry through NMDA receptors and medium- and low-affinity Ca2+ buffers were embedded to corresponding compartments. Ca2+ diffusion within a spine or filopodum was calculated using Fick's equation. Figure 1 shows the overall reaction schemes and the model morphology.
First we simulated the change in the concentration of intracellular calcium ion ([Ca2+]i) in filopodia. The peak [Ca2+]i was increased as the length of filopodium was increased as was expected (Fig. 2 left). However, it was saturated at the filopodium length longer than 1 μm and kept almost the same level. Next, the diameter of a spine head was changed with fixed length of spine neck. With the increase in the spine head diameter, the peak [Ca2+]i was decreased as was expected (Fig. 2 right). However, [Ca2+]i reached a minimum and it kept almost the same level even if the diameter was increased further.
The present simulation results have shown the change in [Ca2+]i with a change in the size of a filopodium and a spine. This suggests that [Ca2+]i can be a triggering molecule for the structural plasticity. The hypothetical mechanism is shown in Figure 3. First, calcium concentration in a localized region of a dendrite is increased forming a 'hot spot'. Second, actin polymerization begins at the 'hot spot' and the protrusion develops increasing the peak [Ca2+]i at its tip. Third, this increase in [Ca2+]i results in further actin polymerization and its bundling. Fourth, protrusion develops further and the peak [Ca2+]i increased. At some level of [Ca2+]i (threshold level), the actin structure at the tip of filopodium is changed from bundling to a meshwork forming a spine head.
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