Effects of KIR current inactivation in NAc Medium Spiny Neurons (Steephen and Manchanda 2009)

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Accession:121060
"Inward rectifying potassium (KIR) currents in medium spiny (MS) neurons of nucleus accumbens inactivate significantly in ~40% of the neurons but not in the rest, which may lead to differences in input processing by these two groups. Using a 189-compartment computational model of the MS neuron, we investigate the influence of this property using injected current as well as spatiotemporally distributed synaptic inputs. Our study demonstrates that KIR current inactivation facilitates depolarization, firing frequency and firing onset in these neurons. ..."
Reference:
1 . Steephen JE, Manchanda R (2009) Differences in biophysical properties of nucleus accumbens medium spiny neurons emerging from inactivation of inward rectifying potassium currents. J Comput Neurosci 27:453-70 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Basal ganglia;
Cell Type(s): Nucleus accumbens spiny projection neuron;
Channel(s): I Na,p; I L high threshold; I T low threshold; I p,q; I A; I h; I K,Ca; I CAN; I A, slow; I Krp; I R;
Gap Junctions:
Receptor(s): AMPA; NMDA; Gaba;
Gene(s): Cav1.3 CACNA1D; Cav1.2 CACNA1C; IRK;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Ion Channel Kinetics; Action Potentials; Synaptic Integration; Delay;
Implementer(s): Steephen, John Eric [johneric at iitb.ac.in];
Search NeuronDB for information about:  AMPA; NMDA; Gaba; I Na,p; I L high threshold; I T low threshold; I p,q; I A; I h; I K,Ca; I CAN; I A, slow; I Krp; I R;
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MSN2009
support_files
beep.bat
delete.bat
Help.txt
                            
INTRODUCTION

This application implements the model described in Steephen, J. E., &
Manchanda, R. (2009). Differences in biophysical properties of nucleus
accumbens medium spiny neurons emerging from inactivation of inward
rectifying potassium currents. J Comput Neurosci,
doi:10.1007/s10827-009-0161-7

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. Toggling ON the 'Beep' button in
the middle panel under RUN CONTROL in the Control Panel will enable
audible alert at the end of each simulation.

For questions and queries, send e-mail to johneric@iitb.ac.in.

FIGURE 1

Fig 1A: The KIR activation time constant curves (tau_m) shown in Fig
        1A for the Existing and Tuned models may be generated as
        follows:Click the 'KIR tau_m...' button in the Control Panel
        (top of middle panel, under CELL PROPERTIES). In the new
        window, toggle the 'Tuned Model' button OFF to turn off the
        tuning. Now click the 'MSP Grapher' button (Right panel, under
        RUN) to launch the Grapher window.  Click 'KIR tau_m' button
        and click 'Plot' to generate the tau_m curve for the Existing
        model. Toggle the 'Tuned Model' button ON and click 'Plot' in
        the Grapher window to generate the tau_m curve for the Tuned
        model.  Fig 1B: The voltage responses may be generated by
        entering current values of -0.227, 0.248 and 0.271 in the
        'amp(nA)' field editor and clicking the 'Execute' Button.

FIGURE 2

Fig 2A: Turn on voltage clamp by toggling ON the 'Voltage Clamp'
        button under INPUT (left panel). Select VClamp in the 'I/V
        Clamp Electrode' window. Set Conditioning Level duration to 10
        ms, and amplitude to -50 mV. Set the Testing Level duration to
        200 ms and amplitude to -120 mV. Set the Return Level duration
        to 1000 ms and amplitude to -50 ms. Click the 'Execute' button
        in the Control Panel. Current response of non-inKir cell to a
        clamp voltage of -120 mV will be plotted. To plot the same for
        the inKir cell, select the 'inKIR' radio button under CELL
        VARIANT in the Control Panel and click the 'Execute'
        button. The clamp responses for other voltages can be
        generated by entering the appropriate voltages in the 'I/V
        Clamp Electrode' window and clicking the 'Execute' button.
Fig 2C: Click 'MSP Grapher'. Click 'gKIR' in the Grapher window. Click
        'Plot' to generate the gKIR curve for the non-inKIR cell. (You
        may have to right click the graph panel and select
        View...->View=plot to see the curve) Select 'inKIR' in the
        Control Panel window and click 'Plot' to generate the same for
        the inKIR cell.
Fig 2D: Click 'MSP Grapher'. Click 'gK' in the Grapher window. Change
        'Indep End' to -60. Click 'Plot' to generate the gK curve for
        the non-inKir cell. Select 'inKIR' in the Control Panel window
        and click 'Plot' to generate the same for the inKIR cell.

FIGURE 3

Fig 3A: These plots can be generated by entering the appropriate
        current values (0.24 to 0.28, -0.2) in the 'amp(nA)' field
        editor in the Control Panel, selecting 'Non-inKIR' or 'inKIR'
        and clicking the 'Execute' button.
Fig 3B: Open the 'Currents' window by clicking the 'Currents' button
        in the Control Panel. Scroll down to the KIR current graph
        panel. Enter appropriate injected current value (0.24 or 0.26)
        in the 'amp(nA)' field editor in the Control Panel. Select
        'Non-inKIR' or 'inKIR' and click the 'Execute' button.
Fig 3C: This figure is derived from Fig 3A.
Fig 3D: To obtain data points for the strength duration curve, select
        'Strength-Duration' under ACTION in the Control Panel
        window. Select 'Non-inKIR' 'under CELL VARIANT. Click
        'Execute'. The NEURON command window will show the injected
        current values (strength) and the corresponding durations once
        the simulation (comprising 10 runs) completes. Select 'inKIR',
        change 'min' under RUN CONTROL to 0.23 and execute again.
Fig 3E: To plot the I-V curve, input 750 in the field editor 'Tstop
        (ms)' under RUN CONTROL, select 'Non-inKIR' or 'inKIR' and
        click 'MSP Grapher' to open the Grapher window. Input -0.3,
        0.2, 10 respectively in the field editors 'Indep Begin',
        'Indep End' and 'Steps' respectively. Set 'Independent Var' to
        'stim.amp' and 'Generator' to 'run()'. Click the 'v' button
        followed by 'Plot'. 10 runs will be performed. Right click the
        graph panel and select View...->View=plot to view the plotted
        curve.

FIGURE 4

Fig 4A: Select one of the cell variants in the Control Panel. Select
        'Min KIR gmax for specified Spike no.' under ACTION. Enter the
        number of spikes in 'No. of spikes' field editor. Click
        'Execute'. The NEURON command window will have the minimum
        gmax value that is needed to generate the specified number of
        spikes for the specified input current.
Fig 4B: Select 'inKIR'. Set inKIR gmax under CELL PROPERTIES to
        0.0014, 0.0012 or 0.0016. Enter values between 0 (No
        inactivation) and 1 (Full inactivation) in 'Inactivation
        level' field editor. Execute and observe spike frequency.
Fig 4C: Select one of the cell variants. Input 0.25 in 'amp(nA)' field editor. Click 'Execute'. 

FIGURE 5

Fig 5A: Select a cell variant. Select the ACTION 'Earliest Spike
        Onset'. Input a value in the 'No. of spikes' field
        editor. Click 'Execute'. NEURON command window will display
        the current corresponding to the earliest spike onset.
Fig 5B & 5C: Derived from Fig 5A.

FIGURE 6

Fig 6A: Select 'Non-inKIR' or 'inKIR'. Input appropriate injected
        current duration in 'dur (ms)' field editor. Select 'Earliest
        Spike Onset' under ACTION. Click 'Execute'. See the NEURON
        command window for the output.
Fig 6B & 6C: Derived from Fig 6A
Fig 6D: Injected current inputs of 0.24741 nA and 0.237 nA to the
        non-inKIR and inKIR cells respectively can generate this
        figure.

FIGURE 7

Fig 7A-D: These plots can be obtained by using the procedures
          described earlier (For Fig 5 & 6). The current plots will
          appear in the 'Currents' window which should be invoked by
          clicking the 'Currents' button prior to execution.
Fig 7E: These can be obtained by executing the program after entering
        the specified values of current and duration.

FIGURE 8

Fig 8A: Select 'Non-inKIR' or 'inKIR'. Activate synaptic input by
        toggling the 'Synaptic input' button ON under INPUT. Specify a
        seed value (eg. 0, 1, 2 etc.) in the 'Seed' field editor under
        RUN CONTROL. Execute.
Fig 8B,C: These are derived from multiple runs using different seed values. 
Fig 8D: Select 'Non-inKIR' or 'inKIR'. Toggle the 'Synaptic input'
        button ON. Enter a value for input up-state frequency in the
        'f(Hz)' field editor under INPUT.  Specify a seed
        value. Execute. Note down the firing frequency for each
        up-state. Repeat for different seeds and input up-state
        frequencies. Calculate the mean firing frequency for each
        input up-state synaptic frequency.
Fig 8E: To obtain the strength duration curve, toggle 'Synaptic Input'
        ON and select 'Strength-Duration' under ACTION in the Control
        Panel window. Select 'Non-inKIR' or 'inKIR' under CELL
        VARIANT. Under RUN CONTROL, input the minimum and maximum
        values of the range of input synaptic up-state frequencies for
        which the strength-duration curve is desired in the 'min' and
        'max' field editors respectively (eg: 5.5 & 10) and set a seed
        value in the 'Seed' field editor.  Input the desired number of
        values within the frequency range for which the duration needs
        to be calculated in the 'iterations' field editor (eg:
        10). Click Execute. The NEURON command window will show the
        input synaptic frequency values (strength) and the
        corresponding durations once the simulation completes for the
        selected seed value. Repeat for different seeds and find the
        mean duration for each input frequency and plot.
Fig 8F: Select 'Frequency Vs Voltage' under ACTION. Execute. Once the
        simulation completes, select 'inKIR' and execute again. Once
        simulation completes, both the plots will be shown in a graph
        window.

FIGURE 9

Fig 9A: Select 'Advanced Run' under ACTION. Execute. Repeat after
        selecting 'inKIR'.
Fig 9B: Select 'Advanced Run' under ACTION. Set 'dur(ms)' to 200,
        'f(Hz)' to 7, 'Tstop(ms)' to 1200. Repeat for 'inKIR'.

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