3D Modeling of Dendritic Spines with Synaptic Plasticity

The protocol develops a three-dimensional (3D) model of a dendritic segment with dendritic spines for modeling synaptic plasticity. The constructed mesh can be used for computational modeling of AMPA receptor trafficking in the long-term synaptic plasticity using the software program Blender with CellBlender and MCell.

Transcript

Computational 3D Geometric Modeling of chemical species reaction through fusion. is a useful method for studying the mechanisms of receptor trafficking in and out of dendritic spine is doing synaptic plasticity. This technique has the advantage of creating a rich environment for making hypotheses and projections about nonlinear systems with a large number of variables.

To create a mesh of a single dendritic spine with a spine head and a spine neck using a modified sphere. First open Blender. With Cell Blender already installed and press 5 on the keypad, to change from the perspective to the orthogonal view.

Press 1 to change to front view and press Shift C to center the cursor. To create the spine head press Shift A to open the Mesh palette, and select the Mesh. Select UV Sphere and in the add UV Sphere, set the size to 0.25 and the rings to 32.

To make the top of the head flat press Tab to switch Blender from the Object mode to the Edit mode. Press B to select the top three quarters of the sphere and press Delete, select Vertices and Enter to remove the vertices. Press B and select the top of the sphere.

Press E, S, 0 and Enter to seal the top of the vertices still selected. And move the blue arrow down to align to the top of the spine head. To increase the mesh resolution at the top of the spine, select Tool and knife and use the knife to cut a circle around the center of the top.

Then select Tool and Loop cut and slide four times to create four concentric circles around the center of the top. To create the spine neck press B and select the bottom of the mesh. Press Delete Vertices and B and select the bottom of the mesh.

Press E and Z and select minus 0.45 to create an extrusion to the Z axis position, at minus 0.45 micro meters. To make the mesh compatible with M-cell press Ctrl T to triangulate the mesh and select Tool and Remove doubles. To create a multiple spine Dendrite press Shift A to open the Mesh palette and select Mesh and Cylinder.

In the Add Cylinder menu, set the radius 0.3 micrometers and the depth to two micrometers and press Enter. Press R and enter 90 to rotate the cylinder 90 degrees and use the blue arrow to drag the cylinder to the bottom of the spine. Press 3 to obtain a front view of the cylinder and press Z to make the mesh transparent.

Use the blue normal arrow to move the base of the spine to the interior of the cylinder and right click to select the Dendrite. Select Modifier and Add Modifier and select Boolean, Operation Union and select Object Spine. Click Apply to create a joint mesh of the Dendrite and the spine.

Then use the mouse to select the mesh of the isolated spine, changing the position and angle to insert each new spine in a physiological position. To create AMPARs, select Molecules and to insert a new molecule. Change the name to AMPAR and change the molecule type to Surface molecule.

Then change the diffusion constant 0.05 times 10 to the eighth square centimeters per second. To plot the anchors bound to the AMPARs, at the PSD1 during the basal condition, open Plot Output Settings and press to define the molecules. Then set the Molecule to Anchor_AMPAR, the Object to Dendrite and the Region to PSD1.

To run a Basal Condition simulation select Run simulation. And set the iterations to 30, 000 and the time step to one times 10 to the minus three seconds. Click Export and Run and wait for the simulation to end.

At the end of the simulation, select Reload Visualization Data, Play animation, Plot output settings and plot to visualize the spatial temporal results. To run the homosynaptic potentiation condition select Molecule Placement and rel_anchorLTP_psd1. Select rel_anchorLTP_psd1 and change Quantity to Release to 200.

Then change Quantity to Release to zero. Select rel_anchor_psd1. Change Quantity to release to zero and run the simulation as just demonstrated.

Synaptic plasticity can be roughly verified through changes in the number of species of AMPARs bound to anchors at each spine. For the exact calculation of the occurrence of synaptic plasticity. It is recommended to calculate the variation of the total numbers of anchored and free AMPARs at the synapse.

AMPAR homosynaptic potentiation and depression can be verified through increases and decreases in the number of anchored AMPARs respectively, caused by changes in the affinity of AMPARs by anchors in comparison to the basal condition. For example homosynaptic long-term potentiation induction at a single spine, creates a heterosynaptic long-term depression effect at the neighboring spines. Following this procedure, the model can be expanded to investigate the process of LTP and LTD induction at Dendritic spines.

This methods allows the testing of hypothesis about the functioning of complex non-linear systems with a large number of variables.

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Journal (Neuroscience)

Journal (Neuroscience)

3D Modeling of Dendritic Spines with Synaptic Plasticity

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