A Simple Model

We start with the most basic model possible so we can focus on introducing you to the core components of the NEURON application and navigating the graphical user interface (GUI).

Part A: “Ball and Stick” model

To introduce the sequence of events involved in setting up a model, we will create an extremely simple neuron consisting solely of a soma and a dendrite called a “Ball and Stick” model.

STEP A1: Launch CellBuilder

CellBuilder is a graphical interface used to generate the basic morphology and biophysics of a neuron.
From the Build menu on the Main Menu window, select CellBuilder and read the descriptions provided.

STEP A2: Create morphology with CellBuilder

First we will specify the two components of our “ball and stick” model: a soma and a dendrite.

1. First, let’s click on Topology
2. The components will be displayed graphically in the white canvas region - a soma is created automatically
3. Create the dendrite component by clicking anywhere on the canvas once
4. This generates a dend section as specified by Basename which is set by default to dend (Hint: click the button to change)

STEP A3: Specify morphological dimensions

The dimensions of the components we created can now be defined in the Geometry window.

NEURON refers to each component as a section. Each section is divided into one or more segments. A segment is the core fundamental unit consisting of a cylinder of uniform electrotonic characteristics based on cable theory.

The soma and dendrite are each cylindrical sections of uniform dimensions. We can now specify exactly what dimensions we would like them to have.

1. Click on Geometry
2. all should be selected by default - if not, select all in the side panel
3. Ensure Specify Strategy is ticked.
4. Select length L, diameter diam from Distinct values over subset
5. Select d_lambda from Spatial grid (This parameter ensures segments are dynamically distributed - see ref 1).

What is Spatial Grid?

Now, we need to specify our lengths and diameters:

1. Unselect Specify Strategy
2. d-lambda is by default set to 0.1 which is suitable for most models
3. In the number box next to soma.L (um), enter 20 as per our table above
4. In the number box next to dend.L (um), enter 1000 as per our table above
5. In the number box next to soma.diam (um), enter 20 as per our table above
6. In the number box next to dend.diam (um), enter 5 as per our table above
7. so that the final result looks like:

STEP A4: Specify biophysical characteristics

The next part of defining the neuron is to specify the biophysical characteristics such as the electrical resistance within the cytoplasm (Ra), the capacitance of the plasma membrane (cm), membrane ion channels, buffers and pumps. NEURON specifies ion channel density by setting the maximum combined conductance (in Siemens) of those channels in that particular segment.

1. Click on Biophysics
2. Ensure Specify Strategy is selected.
3. Ra and cm are uniform in this particular model, so we select the all subset and then click on the Ra and cm checkboxes.
4. We will add a Hodgkin-Huxley (hh) conductance to soma and dend by selecting each then click on hh

Now we will add our values:

1. Now deselect Specify Strategy
2. Select Ra under all and enter 160
3. The default for cm is 1 µF/cm^2 which is fine

Inserting ionic conductances

What is hh?

We will now insert HH into the soma and dendrite.

For the dendrite, we will enter a reduced hh which means altering the standard HH conductances to be 10% of their initial values.

1. Select hh under dend and enter 10% of the Na+ (gnabar_hh) and K+ (gnakbar_hh) conductance values
2. No change to leak current of HH (gl_hh)
3. For the equilibrium potential (el_hh), change this to -64mV

Save Me

You can save this to a file called bs_cell.ses.

1. Set your working directory using the File -> working dir command from the Main Menu window
2. Enter the file path in the window or double-click on folders as they appear. The ../ will return you to the parent directory.
3. Select Move To which sets you up in the correct directory.
4. Under the File -> Save session command, enter the name of the file in the top window (the bottom window is used as a filter only)

STEP A5: Running a simple simulation

We are now ready to load the specifications of our model into the NEURON simulator. We will use the Continuous Create method which is very useful when initially testing a model as it updates parameters in real time.

1. Click Continuous Create in the CellBuilder window
2. We will need to create a stimulus which is known as a Point Process so from the Main Menu window, select Tools -> Point Processes -> Managers -> Point Manager
3. In the PointProcessManager window, click on SelectPointProcess then select IClamp
4. We will accept the default of soma(0.5) which means the stimulus has been placed in the middle of the soma
5. We will insert a 0.6nA current of 1ms pulse width starting at del=5ms (a delay allows for initialization of any conductances with dependencies) so enter the values as shown.

1. Now from the Main Menu window, select Tools->RunControl. This is our stimulus parameter window and is where the simulation is launched.

More about Run Control

1. We will accept the default values, except for the time, so enter 20 for Tstop(ms).
2. To see an output of the simulation, from the Main Menu, select Graph -> Voltage axis
3. Now in the RunControl window, click Init & Run

Have a look in the graph and you should see your neuron respond to the current.

Now we will rerun the simulator to see the effect of increasing the current injection amplitude.

1. In the PointProcess window, change 0.6 to 1.0 in the amp(nA)
2. Now rerun in the RunControl window, by clicking Init & Run and we get a lovely AP.

STEP A6 Save Me

You can save this to a file called bs_iclamprig.ses. (Saving to a new file separates our simulation from our cell.)

Part B: Simple neuron model

We have covered the basics of creating a simple model and simulation. We can now turn our “Ball and Stick” model into a “Simple neuron” by replacing our single dendrite with a tree of branching apical dendrites with the following characteristics:

STEP B1: Reloading sessions

A saved session can now be reloaded with all the parameters and windows already set.

1. Close down the NEURON application via File -> Quit
2. Restart with nrngui
3. You may need to return to your working directory with File -> recent dir
4. Under File -> Load session, select the bs_cell.ses session created above

STEP B2: Modifying neurons

We will now modify the topology of the “ball and stick” neuron.

1. From the CellBuilder, select Topology
2. Select Delete Section then click on dend to remove this

1. Click on Basename and type in ap and Accept
2. Click on Make Section
3. Create two apical dendrite components by clicking anywhere on the canvas (twice!)
4. Add a third dendrite as a branch by click and hold from the joint of the first two dendrites, then drag and release. Errors can be rectified by selecting the commands as required.
5. This generates ap (root), ap[1] and ap[2]

STEP B3: Creating subsets

1. As they share common properties, we will group the dendrite components so click on Subsets
2. Click on Select Subtree
3. Click on the ap segment (root of the subtree)
4. Click on New Section List
5. In the popup window, enter apicals and Accept
6. This new list should appear in the sets.

STEP B4: Modifying parameters - Geometry

We will need to specify the morphological characteristics of the new dendrites

1. Click on Geometry
2. Ensure Specify Strategy is unticked
3. Enter the lengths and diameters of the ap sections as per the table

STEP B5: Modifying parameters - Biophysics

For all the dendrites, we need to enter a reduced HH which means altering the standard HH conductances to be 10% of their initial values.

1. Click on Biophysics
2. Ensure Specify Strategy is ticked
3. Select apicals then tick hh

1. Now untick Specify Strategy
2. Select hh under apicals and enter 10% of the Na+ (gnabar_hh) and K+ (gnakbar_hh) conductance values
3. No change to leak current of HH (gl_hh)
4. For the equilibrium potential (el_hh), change this to -64mV

STEP B6: Save Me

You can save this to a file called simple_cell.ses.

B. EXPERIMENTS

Now it’s time for you to complete the simple neuron. To check you’ve got the hang of it, go back to the CellBuilder and add a basal dendrite and an axon with the following characteristics:

Don’t forget to save your changes to simple_cell.ses

View updated neuron

Resources

Using the CellBuilder

Units in NEURON