This model is a simplified model of one pyramidal cell of the CA3 Field of the Hippocampus and the Long Term Potentiation that it undergoes.
The simplicity of the language and my own programming limitations compromise the accuracy of the model, but it manages to reflect the following :
1) The glutamate molecules are released into the postsynaptic cleft and admitted by both the NMDA and AMPA receptors there found. At this stage, an approximation to the phenomenon of increasing frequency of stimulation was made through an increase in the number of glutamate molecules. This is not biologically accurate, but it helps in the conceptualization of LTP.
2) There are calcium ions constantly trying to enter the pyramidal cell. They are seeking entrance through the magnesium-guarded NMDA ionotropic receptors. These receptors will react to the binding of glutamate and release the magnesium blocking the channel through which the calcium ions can enter.
3) Upon entrance to the pyramidal cell, the calcium ions bind to calmodulin molceules in the cell. This binding activates calcium-calmodulin-dependent kinase II (CaMKII) molecules and they phosphorilate AMPA receptors. This phosphorylation is not shown, nor is the resulting permeabilization of the AMPA receptors to sodium ions. The ease with which the cell responds to stimulus, however, is captured and shown in the plot that accompanies the model.
4) Reuptake takes place and ends each run of the program.
Program created by Miguel Nieto
created with NetLogo
view/download model file: pyramidal.nlogo
WHAT IS IT?
This model is trying to show, in a very simplistic manner, how long-term potentiation takes place in one pyramidal cell in the hippocampus.
The red objects represent approaching axons (2) and the membrane of the pyramidal cell, respectively.
The green objects are calcium ions seeking to enter the pyramidal cell.
The white objects are magnesium ions at the NMDA receptors blocking the entrance of calcium ions.
The blue areas are NMDA receptors.
The magenta areas are AMPA receptors.
The blue objects are Glutamate molecules seeking the NMDA and AMPA receptors.
The yellow objects are CaMKII kinases which, upon binding to the AMPA receptors, make them more permeable to
sodium ions (not shown) and lower the resting potential of the neuron.
The cyan objects are there to represent the impermeability of the AMPA receptor to sodium ions.
In this model, the binding of CaMKII to the AMPA receptors results in the immediate decrease of resting potential. The change in sodium permeability and entrance of sodium to the cell are not explicitly shown.
HOW IT WORKS
Every time this model is used, the neuron will tend to increase its sensitivity to future stimuli. This will not always happen, but over a few runs the plot will show an increase in response to a constant stimulus up until a limit.
HOW TO USE IT
Simply set the strength of the original stimulus to see LTP developing. If the strength is changed, the setup button must be pushed in order
for the model to reflect the changes.
THINGS TO NOTICE
Notice how, with the same impulse and as more impulses are induced, the response by the cell becomes stronger.
EXTENDING THE MODEL
An obvious extension to this model would include interactions of sodium ions with the pyramidal cell.