$ProjectVersion: Release2-2.11 $

Purkinje tutorial
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1. THE PURKINJE CELL
The cerebellar Purkinje cell is the only output neuron from the cerebellar
cortex. It is also among the largest and most complex neurons in the 
mammalian brain. The about 200,000 synaptic inputs received by each Purkinje 
cell constitute the most massive synaptic convergence found on any neuron 
in the brain. Purkinje cells are also distinguished by high densities of 
calcium channels on their dendrite which cause them to easily fire
dendritic calcium spikes. 
The synaptic input to Purkinje cells comes from multiple sources, four of
which are explicitly represented in this model:
 - excitatory input from cerebellar granule cells over their parallel fiber 
   axon. A Purkinje cell receives more than 150,000 such parallel fiber
   inputs onto the spiny dendrite (thin dendrites). Both 'background' 
   (i.e. continuous random) and synchronous parallel fiber inputs can 
   be given.
 - excitatory input from the inferior olive by the climbing fiber input.
   Each Purkinje cell receives only ONE climbing fiber input, which is
   only rarely activated. The single climbing fiber makes multiple
   synapses on the smooth dendrite (i.e. the thicker parts of the
   dendrite). Only synchronous activation is possible.
 - inhibitory input from the cerebellar stellate cells onto most of the 
   dendrite. Only 'background' stellate cell inputs can be simulated.
 - inhibitory input from the cerebellar basket cells onto the proximal smooth
   dendrite and soma. Only synchronous activation is possible.

   

2. MODELING A PURKINJE CELL
A good general introduction of the model can be found at
http://www.tnb.ua.ac.be/publications/pub009/TNB_pub9.shtml, and many other
of our publications about this model are also available. A general overview
of the model scripts can be found at http://www.tnb.ua.ac.be/models/PM9.shtml

This is a compartmental model. The detailed dendritic geometry of the cell
is based on morphological data provided by Rapp, Yarom and Segev which 
is replicated by 1600 electrically distinct compartments. These are 
divided in three functional zones: the soma, the main dendrite and the
rest of the dendrite.

Ten different types of voltage dependent channels are modelled, 8021 
channels in total, using Hodgkin Huxley-like equations based on
Purkinje cell specific voltage clamp data or, when necessary, on data from
other vertebrate neurons. The soma possesses fast (NaF) and persistent (NaP)
sodium channels, low threshold (CaT) calcium channels, and delayed 
rectifier (Kdr), A-current (KA) and non-inactivating (KM) potassium 
channels, and an anomalous rectifier (h1 and h2). The dendritic membrane 
includes P-type (CaP) and T-type (CaT) calcium channels, two different 
calcium-activated potassium channels (BK and K2) and a non-inactivating 
potassium channel. The P-type calcium channel is a high-threshold, very 
slowly inactivating channel, first described in the Purkinje cell and
responsible for the dendritic calcium spikes.

The changes in calcium concentration caused by voltage-activated calcium
influx is computed in a submembrane shell.

3. THE INTERFACE

When the simulation is first run, three windows pop up: the first
window contains a picture of a typical Purkinje cell with buttons on
the right for options on the graphical output.  Beneath the window
with the Purkinje cell is a control panel to do several types of
experiments.  The Output Menu, to the right of the Simulation control
panel, allows you to select what graphs will be displayed.

a. Buttons in the control panel

The buttons in the Simulation control panel fall into three categories :

  1. Buttons for Simulation control: standard GENESIS simulation control

    RESET  
	Resets the simulation and clears the graphical output 
	(unless in overlay mode, see below).

    RUN  
	Initiates the simulation and performs a simulation run for the
        time as given in the time dialog.

    STOP 
	Stops the current simulation (if any)

    QUIT  
	Quits the simulation (and GENESIS).

    Time  (default : 500 msec)
	Sets the total time in milliseconds to be simulated during one
	run (after clicking the 'RUN' button).

    Output rate  (default : 10)
	Sets the output rate for the graphical output relative to the
	simulation time step (which is 0.020 msec).  The default rate
	of 10 means that only once every 10 steps the Purkinje cell
	picture is updated.

  2. Buttons for Simulation mode: Purkinje cell simulation experiments

        (Depending on the cell that you are simulating, some of the
        experiments may not be available.  The following applies if
        you are simulating the 1994 Purkinje cell model of Erik De
        Schutter.)

    Toggle In vivo - In vitro  (default : In vitro)
	This toggle switches between In vitro mode (where there is no 
	background input from stellate cells or parallel fibers) and
	In vivo mode. The Settings window let you set the mean firing
	frequency for stellate (inhibitory) cells and parallel (excitatory)
	fibers. The Settings are only available for the 'In vivo' mode.

    Current injection  (default : on, constant current of 0.5 nA)
	This is a toggle which switches between simulated current
	injection directly into the soma or not. In the Settings
	window the current level (in nano amperes) can be set and a
	choice must be made between constant or current pulses.  The
	current pulses are generated with a pulsegen object.

    Activate parallel fibers
	Hitting this button activates excitatory synaptic input from a 
	specified number of parallel fibers. In the Settings window you 
	can choose the number of parallel fibers that will be activated
	and the relative synaptic strength of each. You can also toggle 
	between activating parallel fibers uniformly distributed over the 
	whole dendritic tree (default) or activating parallel fibers locally 
	on  one specific branch of the tree. In the latter case the number of 
	synchronous activated parallel fibers synapses is preset to 20, 
	for distributed activation the number of activated synapses is cut 
	to a multiple of 25 with a maximum of 475. You can choose the branch
	that will receive local activation by clicking the button
	'Change area from xcell'. Then click anywhere on the spiny dendrite
	of the Purkinje cell, the name of the selected branch will be updated.

    Activate basket axon
	Hitting this button activates inhibitory input from the basket 
	axons that are wrapped around the main dendrite (the thicker 
	dendrite directly attached to the soma) and the soma. The Settings 
	window let you set the relative synaptic strength of all contacts.

    Activate climbing fiber
	Hitting this button activates excitatory synaptic input from the 
	climbing fiber that makes strong synapses on the main and thick
	dendrites. The Settings window let you set the relative synaptic 
	strength and the delay between consequent climbing fiber synapses
	(so it defines the actual speed of signal transmission within the 
	climbing fiber axon).


  3. Buttons for Simulation information

    HELP
	Shows you this information

    CREDITS
	Shows authors and contributors


b. Output windows

There are many output windows: the window with the picture of a Purkinje
cell (the cell viewer), and multiple graph windows that are not visible
when the simulation is started.  The cell and graph windows can be
displayed or hidden by clicking the appropriate toggle buttons in the
output menu.  The use of the graph windows is explained in further detail
below.

  1. The cell output window

        (Depending on the cell that you are simulating, some of the
        output modes may not be available.  The following applies if
        you are simulating the 1994 Purkinje cell model of Erik De
        Schutter.)

	The cell output window displays the value of a calculated variable
	by changing the (rainbow) color of the compartment the variable
	belongs to. Red means a high value, blue means a low value. The
	default is to display the compartmental voltage. It is possible to
	display the calcium concentration or the conductance or current for
	all the types of channels implemented in this Purkinje cell model.
	If a channel or value is not present in a compartment, a default of
	zero is used.

	You select the output type by clicking one of the buttons to the
	upper right of the cell output window.  The simulation will stop
	(simulation time is reset to zero) and GENESIS will take some
	time to change all the display messages. The name of the selected
	variable will appear above the cell and the range of values 
	displayed is shown below the cell (Color maximum or minimum).  The 
	tutorial automatically selects an appropriate range for each
	variable, but you can change this if desired.
	
	For the channels (the synaptic Exc. chan. or Inh. chan, or the 
	voltage-gated CaP, CaT, K2 and so on), an additional choice can 
	be made between channel conductance (Gk button, the default), 
	channel current (Ik button) and for the CaP or CaT channels the 
	reversal potential (Ek button; for the other channels this is 
	constant).  Channel conductance and current can be shown as
	Normalized values (default) or Absolute values.

	For the other possible outputs (compartmental voltage, concentration)
	there are no further options.


    Buttons :

      Comp. Vm
	  Output compartmental voltage (in volts).

      Comp. Ca
	  Output compartmental calcium concentration (in milli molar).

      Exc. chan.
	  Output excitatory synaptic channels.

      Inh. chan.
	  Output inhibitory synaptic channels.

      CaP, CaT, ... h1, h2
	  Output different channel types.  h1 and h2 are two components
	  of the same anomalous rectifier current.

      Ik, Gk, Ek
	  Output current (in Amperes or aribitrary units), conductance
	  (in Siemens or arbitrary units) or reversal potential (in
	  volts) of a channel. These buttons are only available if the
	  main output for the cell is a channel type.

      Output mode : Normalized / Absolute
	  Toggle between Normalized (default) or Absolute values.  For
	  channel types only.  In the Normalized output mode the
	  conductance or current is normalized relative to the surface
	  area of the compartment, this allows you to compare relative
	  activation levels between different compartments (the units
	  are arbitrary). In the Absolute output mode the real values
	  are shown in Amperes (current) or Siemens (conductance);
	  these are typically much larger for large compartments so
	  that changes in smaller ones might not be discernible.

      Electrodes / No Electrodes
	  Toggle between hide (default) / show the recording electrodes 
	  in the cell window.

      Compartment Namer
	  The compartment namer allows to figure out the name of compartments
	  by clicking on the dendritic tree of the cell.

      Color maximum and Color minimum
	  Set the color scales for the cell display.  Updated
	  automatically when a different output is selected.


  2. The graph output windows

	The graph output windows are used to plot membrane potential
	(Vm) and Calcium concentration (Ca) of selected compartments,
	and channel current (Ik), conductance (Gk), or reversal
	potential (Em) for a specified current in the compartment.
	The current is selected with the buttons under "Possible
	outputs" in the cell window, as described above in the section
	on the cell output window.  After a click on a compartment in
	the cell view, each graph will do a best effort attempt to add
	a new plot for the selected compartment.  If the selected
	current does not exist in the compartment, or none was
	selected, the graph windows for Ik, Gk, and Em will indicate
	that this output does not exist.


    Buttons :

      Clear graph
	  Clear the graph and remove all recording sites for this graph.
	  This should be done after changing to a different output in the
	  cell window.  Then, it is necessary to re-select the compartments
	  to be plotted.

      Overlay off / on
	  When a reset is performed, normally all plots are cleared.
	  When overlay is on, they are saved so that you can compare plots
	  from different runs.

      Set scales
	  Allows to set the range of the axes of the graph.  The graph is
	  automatically scaled for the type of the first recording site
	  selected.

      Reset axes
	  Resets the axes to their default values.  The default values
	  are taken from the current active variable in the cell view.
	  If this is not appropriate, push the 'a' key, when the mouse
	  cursor is over the graph to rescale the graph such that all
	  plots fit in the graph.  Next rescale the axes of the graph,
	  using the zoom functions of Xodus : click below the X axis
	  or next to the Y axis to select the region of interest.
	  Note that an appropriate scale is needed to show low
	  amplitude oscillations.


  3. Ascii plots

	The output menu allows to save a variable to a file.  First
	put the cell view in the appropriate mode, next click on the
	cell's dendrite to save the variable for the clicked
	compartment to an ascii file.  The directory where the ascii
	file is saved is 'simulation_sequences/Purkinje/' and the name
	of the file is chosen to match the variable name and the
	compartment name (note : this implies that if you choose the
	same variable twice, the second file will overwrite the first
	file).

