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Using NetCon where voltage is not the threshold variable

Posted: Thu Jun 25, 2020 8:52 am
by Robert Claar

I am an incoming graduate student building a model of a network of endocrine cells and how the hormones they secrete affect each other. Using the NetCon object seemed like a great way to connect the different cell types and weight the connections. I want the cells to read the hormone concentration coming from the other cells at each time step, but this is problematic since the NetCon object has a threshold argument that must be crossed. In my case it is not a voltage that must be crossed for the connection to be made as in a synapse. As of now my lab partner and I have created a dummy variable that oscillates above and below our set threshold so that we can accomplish this, but I was wondering if there was a built in way to do this other than NetCon or if we aren't using NetCon to it's fullest potential for this purpose? Any help is appreciated!

Re: Using NetCon where voltage is not the threshold variable

Posted: Fri Jun 26, 2020 10:33 am
by ted
The NetCon class is useful for spike-triggered synaptic communication, in which it is often reasonable to assume that presynaptic details can be ignored. Signaling that is continuous in time cannot be properly represented with a NetCon. Continuous transmitter release can be implemented with NMODL's POINTER feature, but that is more suitable for interactions between pairs of specific cells.

Hormonal communication would best/most naturally be implemented using extracellular concentrations of chemical signals. This is quite doable with NEURON. You will need a representation of extracellular space that is appropriate for your particular conceptual model and what you want to use it for. Are you treating it as a single "well stirred volume", or as some kind of structured volume with a finite level of detail, or as a continuum?

Re: Using NetCon where voltage is not the threshold variable

Posted: Mon Jun 29, 2020 1:45 pm
by Robert Claar
Thanks Ted,

We would like the hormonal concentration across our endocrine cells to most closely resemble a continuum with every cell being both a source of a hormone and sink of 3 hormones/reaction diffusion species (the hormone the cell secretes + the hormones secreted from two other cell types). The concentration of each hormone is governed by a differential equation in a voltage dependent mechanism/mod file and these differential equations are dependent on the concentration of at least one hormone released from another cell.

For example, the following two equations will exist in the same section/cell:
Glucagon release - G' = JGS/vc-fa*G
Somatostatin (Sst) dependence- rm2a = (1-knockoutda)*ra/(1+exp(-(Sst-sombara)/ssom))+knockoutda*rako)

Is it possible to relate these mechanism variables to a reaction diffusion species, and if so, how would we set it up?

Re: Using NetCon where voltage is not the threshold variable

Posted: Tue Jun 30, 2020 10:44 am
by ted
If your conceptual model of the extracellular space that contains the chemical signals involved just a few compartments, then NMODL might have sufficed. However, if you prefer a continuum, then rxd is probably the best choice. If you could, please open a new discussion thread in the Forum's Reaction-diffusion in NEURON discussion area. That will be most helpful for keeping the Forum's threads organized according to topic.