Glutamate in the synaptic cleft
Posted: Mon Apr 26, 2021 4:53 am
Good morning everybody,
I have a couple of questions about diffusion of molecules in the extracellular spaces. I deeply looked into the forum trying to find something that could have helped me, but I was unsuccessful.
I would like to model glutamate diffusion in the synaptic cleft, with the aim to investigate the spillover effect on a specific (custom) model of AMPA receptor (9-state kinetics) where desensitization is altered.
My system is as follow:
A presynaptic (single compartment) cell, upon stimulation (NetStim), releases glutamate (release.mod from most of Destexhe models), which will then be pumped out in the extracellular space (pump.mod) and can diffuse (RxD) until it reaches the postsynaptic (single compartment) cell. Therefore AMPA receptors (custom AMPA.mod) will be activated depending on the concentration of glutamate they "see".
I have been able to solve most of the issues I run into, but few questions remain.
1) My main question is about the space where my molecules can diffuse. I set an extracellular space which includes the "points" where the release of glutamate occurs and where my AMPA receptor sit.
If glutamate is diffused in the cleft, will the molecules see the pre- and postsynaptic cell membrane "as obstacles" and then bounce? Or does the diffusion occur in the entire extracellular space I set, no matter what else is there?
I know that I can set volume_fraction and tortuosity values in order to have a kind of control on the diffusion, but as far as I understood, this doesn't allow me to select exactly which region of the extracellular space (I mean in terms of x,y,z coordinates) my molecules are not allowed "to go" to.
2) Following the first question, a possible work around would be, as far as I understood, to set the diffusion_coefficient as a function of coordinates (anisotropic diffusion). But so far the anisotropic diffusion in the extracellular space seems to be not supported yet. I tried the K+ diffusion example, and the anisotropic diffusion didn't work. Is there a way to work around this issue?
I hope my questions are clear. Thank a lot in advance!
Cheers
I have a couple of questions about diffusion of molecules in the extracellular spaces. I deeply looked into the forum trying to find something that could have helped me, but I was unsuccessful.
I would like to model glutamate diffusion in the synaptic cleft, with the aim to investigate the spillover effect on a specific (custom) model of AMPA receptor (9-state kinetics) where desensitization is altered.
My system is as follow:
A presynaptic (single compartment) cell, upon stimulation (NetStim), releases glutamate (release.mod from most of Destexhe models), which will then be pumped out in the extracellular space (pump.mod) and can diffuse (RxD) until it reaches the postsynaptic (single compartment) cell. Therefore AMPA receptors (custom AMPA.mod) will be activated depending on the concentration of glutamate they "see".
I have been able to solve most of the issues I run into, but few questions remain.
1) My main question is about the space where my molecules can diffuse. I set an extracellular space which includes the "points" where the release of glutamate occurs and where my AMPA receptor sit.
If glutamate is diffused in the cleft, will the molecules see the pre- and postsynaptic cell membrane "as obstacles" and then bounce? Or does the diffusion occur in the entire extracellular space I set, no matter what else is there?
I know that I can set volume_fraction and tortuosity values in order to have a kind of control on the diffusion, but as far as I understood, this doesn't allow me to select exactly which region of the extracellular space (I mean in terms of x,y,z coordinates) my molecules are not allowed "to go" to.
2) Following the first question, a possible work around would be, as far as I understood, to set the diffusion_coefficient as a function of coordinates (anisotropic diffusion). But so far the anisotropic diffusion in the extracellular space seems to be not supported yet. I tried the K+ diffusion example, and the anisotropic diffusion didn't work. Is there a way to work around this issue?
I hope my questions are clear. Thank a lot in advance!
Cheers