### Fitting a single tau1 and tau2 in k3.mod

Strategy:
Set up a single compartment model with the khh channel inserted. Stimulate with a voltage clamp. Use the MultipleRunFitter with a "Run Fitness" generator to fit g_khh vs t to the 109mV conductance time course by optimizing ta1 and ta2 in k3.mod with tk1=tk2=0.

The completed example can be run by executing the k3taufit1.hoc file.

1) Run nrngui and build a single compartment. Make sure the k3.mod file is one of the "Additional mechanisms."

2) Insert the khh mechanism into the patch.

3) Insert a SEClamp (single electrode clamp) point process into the patch and set it up with dur1=0, amp1=0, dur2=100, and amp2=109. Hint: later on we'll be using dur1 to define an initial delay.

4) Observe the membrane potential during a run to verify that the voltage clamp is operating correctly. You may wish to reduce the rs of the SEClamp.

5) Load the data, i.e. load hh508.hoc .

6) Pop up a multiple run fitter instance. Add a generator of type "Run Fitness" and name it "109". Display the generator and select a variable to fit of soma.g_khh(.5). Close and re-display the generator so it pops up with the proper size. Pick the 109 data curve and put it into the generator graph.

7) Selecting the Generator's Fitness/ProtocolConstant will pop up a symbol chooser. Show "Objects" and select SEClamp_[0].amp2. Close and re-display the generator so it pops ups with the proper size. Notice that the string "109" should be in three places within this generator: The name of the generator, the value of the protocol constant, and the name of the data vector. Of course, only the protocol constant value is substantive, but later on we'll be adding more generators for different voltage levels and consistent mnemonic names will help distinguish them properly.

8) Press the ErrorValue button in the generator. You'll get an error in the terminal window complaining about a vector argument being too small in meansqerror. The problem is that the run is not long enough to span the data. Pop up a control panel and change tstop to 12. While you're at it change the Init field editor (v_init) to 0. The generator is set properly if it can calculate an error value between model and data.

9) Add four parameters. ta1_khh, tk1_khh, ta2_khh, and tk2_khh. Pop up a parameter panel and turn off the optimizing of tk1 and tk2 and set their values to 0. Pop up a domain panel and select GroupAttributes/PositiveDefiniteLimits" followed by GroupAtrributes/UseLogScale

10) Calculate the total error value from the MulRunFitter main panel. If it is 0 you forgot to turn on the generator.

11) Pop up an Optimizer panel, press Optimize, and see what happens for a while.

12) The fit is poor because the model cannot produce the long initial delay. Add a new protocol constant to the generator for SEClamp[0].dur1 and set it to 0.3 . Re-optimize. The fit is much more pleasing. What is your judgment as to the physical meaning of this artifice?

13) Clone the generator and name the new one "32". Make it the one being added to the error function and don't use "109". Return to the Display mode close the old Generator panel and show the new "32" generator. It is the same as "109" except for it's name. Replace the data with the 32mV conductance data and change the amp2 protocol constant to 32. Note: To clone, select Generators/CloneGenerator and double click on the "109" generator. To re-name the new one, select Generators/ChangeName and double click on the new one. To conveniently select the new one for use and NOT use the old one, select Generators/PopUp"Use"Panel and checkmark the appropriate subset.

14) Optimize the "32" data. What if the dur1 protocol constant is 1?

15) Save this session. It will be used in the next exercise.

NEURON hands-on course
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