3D Modeling of Dendritic Spines with Synaptic Plasticity

Summary

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.

Abstract

Computational modeling of diffusion and reaction of chemical species in a three-dimensional (3D) geometry is a fundamental method to understand the mechanisms of synaptic plasticity in dendritic spines. In this protocol, the detailed 3D structure of the dendrites and dendritic spines is modeled with meshes on the software Blender with CellBlender. The synaptic and extrasynaptic regions are defined on the mesh. Next, the synaptic receptor and synaptic anchor molecules are defined with their diffusion constants. Finally, the chemical reactions between synaptic receptors and synaptic anchors are included and the computational model is solved numerically with the software MCell. This method describes the spatiotemporal path of every single molecule in a 3D geometrical structure. Thus, it is very useful to study the trafficking of synaptic receptors in and out of the dendritic spines during the occurrence of synaptic plasticity. A limitation of this method is that the high number of molecules slows the speed of the simulations. Modeling of dendritic spines with this method allows the study of homosynaptic potentiation and depression within single spines and heterosynaptic plasticity between neighbor dendritic spines.

Introduction

Synaptic plasticity has been associated with learning and memory¹. Synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), is associated respectively with the insertion and removal of AMPA receptors (AMPARs) in and out of the synaptic membrane². The AMPAR synapses are located on top of the small volume structures called dendritic spines³. Each spine contains a protein dense region in the postsynaptic membrane called the postsynaptic density (PSD). Anchor proteins at the PSD trap AMPARs in the synaptic region. There are few copies of AMPARs within a single synapse ....

Protocol

NOTE: Please see the Supplementary file 1 for the glossary of terms used in this protocol.

1. Install Blender, CellBlender, and MCell

NOTE: This protocol requires installation of MCell, Blender, and Cell Blender.

1. Download and install the software on the MCell homepage (https://mcell.org/tutorials_iframe.html). Go to downloads on the top of the page and then follow the step-by-step instructions to download and install the software in the environment of choice (e.g., Linux, Mac OSX, or Windows).
   NOTE: All computational models and simulations described in this protocol were tested....

Results

These results provide the steps for the construction of a 3D mesh that simulates a dendritic spine with a spine head and spine neck (Figure 1 to Figure 4). In addition, multiple dendritic spines can be inserted in a single dendritic segment (Figure 5) to study heterosynaptic plasticity of AMPARs¹⁴. The PSD on the top of the spine head (Figure 6) is the place where synaptic anchor.......

Discussion

This article presents a method for the construction of 3D meshes for modeling reaction-diffusion synaptic plasticity processes in a dendritic segment with dendritic spines. The developed model contains a dendritic segment with few dendritic spines. The lateral diffusion and reaction of AMPARs with synaptic anchors allow the simulation of the basal dynamics. The critical steps in the protocol are cutting the sphere for the creation of the top of the spine head (Figure 1, .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Blender	Blender Foundation		https://www.blender.org/
CellBlender	University of Pittsburgh		https://mcell.org/
Mcell	University of Pittsburgh		https://mcell.org/