INTRODUCTION

This application implements the model described in Steephen, J. E. (2009).
Excitability range of medium spiny neurons widens through the combined
effects of inward rectifying potassium current inactivation and dopaminergic
modulation. Neurocomputing, 74.18 (2011): 3884-3897 

This help window provides instructions for replicating the results in
the paper. The information in this window is available in the text
file 'Help.txt' within the 'support_files' folder. If required, it
could be printed for easy reference. Launching the program (main.hoc)
invokes 4 windows: NEURON Main Menu, Command Window (nrniv), the
Control Panel and a Graph Window. Note that the Control Panel is
organized into 3 vertical panels. The instructions given below for
each figure assume that the application is in its default settings. It
is recommended that the application be restarted after each simulation
as it would reset all parameters to their default values. Note that
you may have to right click the graph panel and select View...>View=plot 
to view some of the plots. 

For questions and queries, send e-mail to john.steephen@duk.ac.in.

THE SUMMARY FILE

In the project folder, you will find a text file named Summary.txt. 
This file contains the summary of the last completed simulation protocol. 
This summary file is updated at the end of every simulation. If multiple
simulations were conduced during one session, only the summary of last 
simulation procedure is maintained. Note that one simulation protocol 
might contain multiple iteration of cell-stimulation, each time varying
a setting, as required by the protocol. Thus, one instance of simulation 
protocol is started when the "START" button is pressed and finished when
the message "Summary.txt Updated" is shown in the Command Window.
The Summary file is not updated if the user press the "STOP" button to 
abort the simulation protocol. 

A copy of the Summary.txt is also created at the end of each simulation.
By default, this file is kept in the folder support_files as a file 
named Output.txt. The name of this backup file can be updated by the user 
at any point of time, by clicking the "Save to..." button under the RUN 
section of the control panel. When the simulation gets over, the Summary 
file is first updated, and a copy will be made on the User-given file.
This feature is very useful if a user intends to run multiple simulation 
procedures one after another. The "Save to.." button is pressed before 
pressing "START" button to update the output file. 

The procedure to generate each of the figures shown in the reference 
paper is given below. Many of the figures are generated with the help
of the Summary file. 

FIGURE 1

Figure one shows the spiking behavior of MSP neuron with different
cell properties under intrinsic modulation conditions. 
The voltage recordings (in mV) are obtained from the cell soma and 
plotted against time in ms. 

Fig 1A: (a) In control panel, 
    > Click on Synaptic input under INPUT section
    > Click on START button
    The plot obtained in the graph is the required output

    (b) In control panel,
    > Click on the inKIR radio button under CELL PROPERTIES
    > Click Synaptic input statusbutton
    > Click on the START button
    The plot is obtained in the graph window. 

Fig 1B: (a) In control panel,
    > Click on D1 radiobutton under DA Receptor Variant
    > Click on radiobutton "Intrinsic" Under DA Modulation Setting
    > Click on Synaptic input statusbutton
    > Click on the START button
    The plot is obtained in the graph

    (b) In control panel,
    > Select inKIR radiobutton
    > Select D1
    > Select Intrinsic
    > Turn on Synaptic input
    > START simulation
    Plot is obtained in Graph

Fig 1C: (a) Same as 1B(a), except that D2 is chosen instead of D1
    (b) Same as 1B(b), except that D2 is chosen instead of D1


FIGURE 2

This figure shows the variation in the no on spikes per up-state
with respect to the variations in cell properties and under intrinsic
modulation conditions. 
There are no subfigures, but the six points and the corresponding 
error bar shown in the figure needs to be obtained using six separate
simulations. As an example, the procedure to obtaine the fourth point, 
labeled inKIR+D1 is given below:

    In control panel
    > Select inKIR
    > Select D1
    > Select Intrinsic DA Modulation
    > Turn on Synaptic input
    > Set iterations = 30 (under ACTION)
    > Press "Save to..." button and set output file as Output2.txt
    > Click START to start the simulation
      (This will take some time. You may close the Graph panel 
      to speed up the simulatio)

When the message "Simulation Complete" appears in the command window,
open the file Output1.txt. In that file under ACTION and RESULTS section,
the mean and the s.e.m of the No. of spikes per Up-state is provided. 
(Took me 5.5 mins to finish simulation and the values obtained are
Mean = 3.2 and s.e.m = 0.1)
These are the values plotted as fourth point and its error bar in Fig. 2. 
Similarly the rest of the points can be generated. 


FIGURE 3

This is a figure derived from Fig. 2 described above. 


FIGURE 4

Fig 4A: Spike frequency vs Current Injection amplitude under intrinsic
    dopamine modulation conditions.

    For each line shown in the figure, one separate simulation
    is needed. As an example, describing the procedure to produce 
    the plot curresponding to non-inKIR D2.

    In control panel,
    > Select D2
    > Select Intrinsic
    > Select 'Range Run' radiobutton under ACTION
    > set min = 0.21
    > set max = 0.3
    > set iterations = 19
    > Press "Save to..." button and set output file as Output4a.txt
    > Click START to start the simulation

    When "Simulation Complete" message appear in the command window, 
    open the file Output4a.txt. You can find a table showing the IC 
    amplitude and the corresponding spike frequency. This can be 
    plotted using plotly, python, MS Excel, Origin, or whatever 
    plotting software you are comfortable with. 

    The other lines in Fig. 4A can be produced by varying the cell
    properties, but maintaining the settings of the INPUT section 
    and the ACTION section unchanged.

Fig 4B: Spike frequency vs input Up-state frequency under intrinsic
    dopamine modulation conditions. 

    This is similar to the procedure in Fig. 4A, but there are some 
    changes in INPUT and ACTION section settings. Describing the
    procedure to produce plot corresponding to non-inKIR D2. 
    Marking (*) wherever there are changes from the procedure in 
    Fig. 4A above

    In control panel,
    > Select D2
    > Select Intrinsic
    > (*) Turn on Synaptic input
    > Select 'Range Run'
    > (*) set min = 5
    > (*) set max = 8.5
    > (*) set iterations = 15
    > Press "Save to..." button and set output file as Output4b.txt
    > Click START (long simulation: close the graph for better speed)

    When "Simulation Complete", open the Output4b.txt file, where 
    you will find the table showing the variation of spike frequency
    vs the input up-state frequency. Use a convenient plotting 
    tool to visualize the plot. 


FIGURE 5

This figure is generated using a procedure exactly identical to the Fig. 2. 
After generating the Output file through the simulation, open the file and
observe the mean and s.e.m. of the Spike Onset Time given in the ACTION and
RESULTS. This value represent one point in the Fig. 5, corresponding to the
Cell Properties mentioned in the simulation. The process can be repeated 
for different cell properties and the rest of the points can be plotted. 

If the output files used to obtain Fig. 2 is available, there is no need 
to redo the simulation to obtain Fig. 5

FIGURE 6

This figure is generated from the data of Fig. 5. No separate dimulation 
needed. Thus the series of simulations conducted to generate Fig. 2 can
produce data for preparing Figs 3, 5, and 6 as well.

FIGURE 7

Identical procedure as in Fig. 1 - except one setting: 
    > Intrinsic-synaptic option is selected for dopamine modulation

FIGURE 8

Identical procedure as in Fig. 2 - except one setting: 
    > Intrinsic-synaptic option is selected for dopamine modulation

FIGURE 9

Data from Fig. 8 is used to prepare this figure.

FIGURE 10

Identical procedure as in Fig. 4 - except one setting: 
    > Intrinsic-synaptic option is selected for dopamine modulation

FIGURE 11

Identical procedure as in Fig. 5 - except one setting: 
    > Intrinsic-synaptic option is selected for dopamine modulation