EXERCISES TO ACCOMPANY THE NEURON TUTORIAL The simulation loads with a number of defaults set. You should see six graph windows on your screen. For purposes of this assignment, the upper left window is #1. We will number the rest of the windows COUNTER-CLOCKWISE so that the window in the upper right corner is #6. Window number #6 will not always be present. Under the graph windows are a bunch of "buttons" and dialogue boxes. Move the mouse cursor to the button labeled "Step". This button starts the simulation. Click the left mouse button on "Step". (Normally you will click on "Reset" first.) The default simulation will begin. In window #1, there are three stimuli: one long square pulse and two strings of impulses. From the top they are: "Source B", "Source A" and the "soma injection current". In a dialogue box below you will see that the injection current is set to 0.0002. To the right of that you will see that synaptic weights for all the sources and dendrites are set to 0.0. Therefore, only the injection current is currently stimulating the cell. (Call up help and click on "neuron inputs" for a drawing of the model cell.) Study windows #2 through #5 until you understand what is going on. QUESTION 1: In 20 words or less, what is the relationship between what you see in window #4 and window #3? Why do you see action potentials in window #3 (Dendrite #1 Vm)? Move the mouse cursor into the dialogue box for the soma injection current. Backspace (key) once. This should delete the "2" and leave only "0.000" show- ing. Hit "return". (NOTE: you must hit "return" after changing the contents of a dialogue box. If you don't, the number will show as changed, but the new value will not be installed and you will get an incorrect simulation.) Click on "Reset" and then "Step". You should get a lot of straight lines. Make sure you understand what you've just done. Leave the soma injection current set to zero. Set the synaptic weight for dendrite #1 excitatory input to 12 and make sure it is toggled to "Source A". Click on the button labeled "inputs". This will bring up a menu of dialogue boxes for some input parameters. Look at the parameters and relate them to the plots in window #1. Note that the "Source A interval" is set to 10. Put the menu away and "Step" the simulation (Click on "Reset" first). Study what you see. Open the "input" menu and change "Source A interval" to 3 (Don't forget to hit "return". Click on "Done". Toggle "overlay mode" on. Click on "Reset" then "step". You should get the result of the second simulation overlayed on the first. Leave overlay on and repeat for "Source A intervals" of 2, 1, and 0.5. Watch each set of curves form so that you know where each tracing came from. If you screw up or need to run the simulations again, just toggle overlay off, hit reset and begin again. QUESTION 2: In 10 words or less, what principle does the overlayed plot in window #2 demonstrate? (There is a two-word phrase for this.) QUESTION 3: Make a plot of the input-output transfer function. That is, plot output rate vs input spikes rate. (To make a more accurate estimate of the output spike interval, you may wish to use the "SCALE" button in the upper left corner of the graph to change xmin and xmax.) Now set the "Source A interval" to "2", keeping it connected to the excitatory input of dendrite #1 with a synaptic weight of 12. Set the synaptic weight for dendrite #1 inhibitory input to 12 and make sure that it is toggled to "Source B". Leave everything else as it was. "Reset" and "Step" for a new simulation. You should note that the inhibitory input has little effect upon the generation of action potentials. QUESTION 4: Using only the "synaptic weight for dendrite #1 inhibitory input" and the three "Source B" parameters (delay, width and interval, inhibit (suppress) the middle of the three action potentials produced by "Source A" input. You may not modify any "Source A" parameters, and both the first and last action potentials must remain. Answer the question by stating the parameter values you had to use and by submitting hard copy of window #2 if your system allows you to make prints of the screen. Toggle "Plot Soma" to "Plot Dendrite 2". Move the inhibitory input ("Source B") to Dendrite #2. QUESTION 5: For the above configuration, is the inhibitory synapse more or less effective at suppressing the middle action potential? Defend your answer with numbers by varying the synaptic weights used in this configuration and the previous one. Give reasons for the results which you see. Reverse the inputs. That is, place the excitatory input on dendrite #2 and the inhibitory input on dendrite #1. QUESTION 6: For the above configuration, is the inhibitory synapse more or less effective at suppressing the middle action potential? Defend your answer in the same manner as in QUESTION 5, and explain the differences between this situation and the previous one. There is a dialog box called "Cable Compts.". It lets you add a number of cable segments between dendrites 2 and 1. (If you wish, you may try using this to exaggerate the effects seen in questions 5 and 6.) Now apply a sub-threshold EPSP to the distal dendrite section (Dendrite #2). QUESTION 7: Using various numbers of inserted segments, estimate the length constant, "lambda", for this dendrite. Express your answer in units of "number of segments" and compare your result with the predictions of theory. (HINT: Use the "SCALE" button to change ymin and ymax to suitable values for accurate measurement of the evoked potentials. The "Cell Parameters" menu will tell you the values of relevant dendrite parameters.)