How to program plasticity?

[Randy]

Hi, I'm a beginner in NEURON. Could any one tell me how to simulate plasticity, which means change parameters by some rule with the simulation progress? From the tutorial documents, I learned how to set every parameter and run a simulation but I don't know how to make them changable.
Thank you!

[ted]

Depends on what you want to change, and the rule that will govern the change.

[argunsah]

Hello, I am also interested in this topic.

What I would like to do is to simulate glutamate uncaging experiments for two reasons:

1) I would like to mimic glutamate uncaging at different spatially located spines and investigate the information processing in soma.
2) Depending on the applied stimulus (amount of glutamate entering the cell, Ca++, Na and K dynamics), modeling the structural plasticity (it doesn't have to be in the level of actin dynamics but I want the number of membrane receptors to change) and to see function implications.

One of my main purposes is to model cooperation and competition phenomena between spines during learning (effect of plasticity related proteins and their spatio-temporal dynamics to LTP and LTD).

When I say structural plasticity, I meant physical changes in a spine as its being stimulated by glutamate uncaging. I want to model Glutamate - NMDAR interactions , calcium dynamics and addition or internalization of AMPARs and actin mechanism.

Cooperation is when one spine is stimulated with a subthreshold stimulus after its nearby neighbor was stimulated with a strong stimulation, the weakly stimulated spine increases its volume as if it was strongly stimulated.

Competition when two spine which are 10-70μm apart from each other strongly stimulated simultaneously caused both spines to potentiate slower suggesting that there is a competition between spines for limited resources at the dendritic branch.

What should be the path I should follow in order to address these questions using NEURON, if it is possible to address them using NEURON?

Thank you very much,

[ted]

First, let me thank you for your interest in NEURON.

What should be the path I should follow in order to address these questions

The phenomena can be simulated with NEURON. Before settling on a simulation environment or attempting a computational implementation, you first need to come up with a conceptual model that can be implemented in computational form.

This means construction of a clear conceptual model of what you judge to be relevant to the phenomena of interest. It involves identifying and describing the relevant anatomical structures, reactive species that are involved, and the interactions between them.

Your particular interests imply a focus on the molecular machinery in spines: transmitters, messengers, receptors, enzymes, transporters/exchangers/pumps, and relevant cytoskeletal elements; chemical reactions between these entities; and their spatial locations and relevant structural factors (physical separations that require diffusion, barriers that may interfere with diffusion, compartments such as intracellular stores or extracellular spaces). Lots of very interesting stuff to include in the kind of diagrams that get published in articles, and good to keep in mind as your long-term target.

But when starting to design your first conceptual model that is suitable for computational modeling, it is necessary to avoid the temptation to include everything. Be selective! If the conceptual model is too complex, it will be intractable because of lack of experimental basis for setting parameters, and there is a risk of having so much mechanistic complexity that it becomes impossible to develop understanding (even with the aid of computational modeling). Understanding begins with simplification--remember how you learned chemistry, physics, math. Add complexity only as needed to improve understanding.

It is best to follow a cycle of iterative testing and refinement

Code: Select all

start with a conceptual model that is relatively simple
Repeat
  learn what you can from it by wet lab experimentation, mathematical analysis,
    and/or computational modeling
  based on what you learned:
    develop a new conceptual model that incorporates refinements and a few new complexities
      that you deem necessary
Until (you are satisfied with the latest version of the model) OR (funding stops)

1) I would like to mimic glutamate uncaging at different spatially located spines and investigate the information processing in soma.
2) Depending on the applied stimulus (amount of glutamate entering the cell, Ca++, Na and K dynamics), modeling the structural plasticity (it doesn't have to be in the level of actin dynamics but I want the number of membrane receptors to change) and to see function implications.

This can all be done with NEURON.

When I say structural plasticity, I meant physical changes in a spine as its being stimulated by glutamate uncaging. I want to model Glutamate - NMDAR interactions , calcium dynamics and addition or internalization of AMPARs and actin mechanism.

This can also be done with NEURON, including simulation of competition and cooperation.

NEURON makes it easy to avoid having to deal with the cable equation. Representation of ion accumulation and chemical reactions can be specified using kinetic schemes as described in chapter 9 of The NEURON Book; when you get to this stage, you'll probably want to consult or collaborate with someone who is experienced with NMODL.