Nothing happens--the number in the field next to the Error Value button is still 0.
We have to tell the MRF to use our Generator. Look at "iclamp soma" in the right hand panel of the MRF. See the little - (minus) sign? That means we haven't told the MRF to use the iclamp soma Generator.
To fix this, in the MRF click on
Generators / Use Generator
and note the appearance of "Toggle" next to the Generators button.
Double click on "iclamp soma" in the right panel of the MRF,
and the - changes to a + (plus).
Now when we click on the MRF's Error Value button, the iclamp soma Generator will run a simulation and contribute to the total error that appears in MRF's error value field.
This brings up a MulRunFitter Optimize panel, which we'll call the "Optimize panel". Change the "# quad forms before return" (numeric field near the bottom of the Optimize panel) from 0 to 1.
Now click on the Optimize button in this panel.
When the MRF stops, note the error value, then click on Optimize again.
And again.
Does it seem to be stuck?
Watch the values in the parameters panel--do any of them occasionally go negative?
Try constraining the parameters
It would be meaningless for any of the actual biophysical parameters (Ra, cm, g_pas, A0, and A) to become negative. And a negative value for d (distance at which membrane conductance is halfway between A0 and A) would also make no sense.
So all of the parameters are positive definite.
To apply this constraint,
bring up the MRF's Domain panel by clicking on its
Parameters / Domain Panel
In the MulRunFitter Domain panel click on
group attributes / positive definite limits
Now do a few more optimization runs.
The error decreases very gradually, and NEURON's interpreter
prints a lot of complaints about parameters trying to go negative.
What else can we try?
The PRAXIS optimizer often benefits from logarithmic scaling of parameters. This seems to be most helpful when two or more parameters are very different in size, i.e. when they differ by orders of magnitude. Which is the case in this problem.
To apply logarithmic scaling to all the parameters,
in the MulRunFitter Domain panel click on
group attributes / use log scale
Click on Optimize once more . . . much nicer!
Range constraints and log vs. linear scaling can also be set for individual parameters. Just double click on a parameter in the Domain panel, then change the contents of the edit field in the window that pops up--see the "DomainPanel" discussion in the Programmers' Reference entry about the MulRunFitter.For an expanded discussion of parameter constraints, see D. Constraining parameters at http://www.neuron.yale.edu/neuron/static/docs/optimiz/func/params.html
Follow similar steps to retrieve the dendritic membrane potential recording and paste it into the Generator.
Finally, try using both Generators together and see if you get a better result, or at least faster convergence.
Hints: