Cerebellar purkinje cell (De Schutter and Bower 1994)

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Accession:7176
Tutorial simulation of a cerebellar Purkinje cell. This tutorial is based upon a GENESIS simulation of a cerebellar Purkinje cell, modeled and fine-tuned by Erik de Schutter. The tutorial assumes that you have a basic knowledge of the Purkinje cell and its synaptic inputs. It gives visual insight in how different properties as concentrations and channel conductances vary and interact within a real Purkinje cell.
References:
1 . De Schutter E, Bower JM (1994) An active membrane model of the cerebellar Purkinje cell. I. Simulation of current clamps in slice. J Neurophysiol 71:375-400 [PubMed]
2 . De Schutter E, Bower JM (1994) An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses. J Neurophysiol 71:401-19 [PubMed]
3 . Staub C, De Schutter E, Knöpfel T (1994) Voltage-imaging and simulation of effects of voltage- and agonist-activated conductances on soma-dendritic voltage coupling in cerebellar Purkinje cells. J Comput Neurosci 1:301-11 [PubMed]
4 . De Schutter E, Bower JM (1994) Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs. Proc Natl Acad Sci U S A 91:4736-40 [PubMed]
5 . De Schutter E (1998) Dendritic voltage and calcium-gated channels amplify the variability of postsynaptic responses in a Purkinje cell model. J Neurophysiol 80:504-19 [PubMed]
6 . Jaeger D, De Schutter E, Bower JM (1997) The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: a modeling study. J Neurosci 17:91-106 [PubMed]
7 . de Schutter E (1994) Modelling the cerebellar Purkinje cell: experiments in computo. Prog Brain Res 102:427-41 [PubMed]
8 . De Schutter E (1997) A new functional role for cerebellar long-term depression. Prog Brain Res 114:529-42 [PubMed]
9 . Steuber V, Mittmann W, Hoebeek FE, Silver RA, De Zeeuw CI, Häusser M, De Schutter E (2007) Cerebellar LTD and pattern recognition by Purkinje cells. Neuron 54:121-36 [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:
Cell Type(s): Cerebellum Purkinje GABA cell;
Channel(s): I Na,p; I Na,t; I T low threshold; I p,q; I A; I K; I M; I K,Ca; I Sodium; I Calcium; I Potassium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: GENESIS;
Model Concept(s): Activity Patterns; Dendritic Action Potentials; Active Dendrites; Detailed Neuronal Models; Tutorial/Teaching; Synaptic Integration;
Implementer(s): Cornelis, Hugo [hugo at bbf.uia.ac.be]; Airong, Dong [tard at fimmu.com];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,p; I Na,t; I T low threshold; I p,q; I A; I K; I M; I K,Ca; I Sodium; I Calcium; I Potassium;
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.bbf.uia.ac.be/publications/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.bbf.uia.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, two windows pop up : the first 
window contains a picture of a typical Purkinje cell with on the right 
buttons for options on the graphical output. Beneath the window with the 
Purkinje cell is a control panel to do several types of experiments.


a. Buttons in the control panel

The buttons in the Simulation control panel fall apart in 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 millisec).  The default 
	rate of 10 means that only once every 10 steps the Purkinje 
        cell picture is updated.

    Toggle Simulation time  (default : off)
	Allows you to display the simulation time in seconds as the 
	simulation progresses.  This usually slows down the simulation.

  2. Buttons for Simulation mode: Purkinje cell simulation experiments

    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 nanoAmperes) can be set and a choice must be made between 
	constant or current pulses. For the current pulses the pulse 
	amplitude (nA), width (msec) and period (msec, this is the period
	between onset of two consecutive pulses) can be set in the 
	appropriate dialogs.

    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 two output windows : the window with the picture of 
a Purkinje cell (the cell output window) and a graph window that is not 
visible when the simulation is started (the graph output window, to open it
click 'graph' button in the cell output window).


  1. The cell output window

	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. Default 
	is to display 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 messaged. 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.

	Besides the colorfull output of variables, the tutorial lets
	you follow the change of a particular variable in the graph window. 
	To make the graph window visible, click the 'Graph' button once in the
	cell window. To follow a particular variable you are interested in 
	(e.g. calcium concentration in the main dendrite) set the cell output
	window into the mode that colorizes the Purkinje cell to follow the 
	variable you are interested in (i.e. click to 'Comp. Ca' button to
	visualize calcium concentration in the compartments). Now click 
	the add plot button in the graph window and click then on the main 
	dendrite in the cell window, the graph will respond with an output 
	of the form 'main_7_Ca' (the number could be different). If 
	you now run a simulation, the graph window will show the compartmental
	calcium concentration in the main dendrite. When several plots are 
	made in the same simulation, the color of the plots can be used 
	to differentiate between them and to associate every plot with an 
	electrode in the cell window (the electrodes are made visible by 
	clicking the 'Electrodes' button in the cell window).  When you 
	change the cell output mode to one that uses the same units the
	current selected graphs will remain active (e.g. changing the cell
	output from CaP conductance to CaT conductance), otherwise they
	will be cleared (e.g. from CaP conductance Comp. Ca).


    Buttons :

      Comp. Vm
	  Output compartmental voltage (in volts).

      Comp. Ca
	  Output compartmental calcium concentration (in milliMolar).

      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 aribitrary 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
	  aribitrary). 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.

      Graph / No Graph
	  Toggle between hide (default) / show the graph output window.

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

      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 window

	The graph output window lets you follow the change of a particular 
	variable during a simulation. For more explanation on how to choose 
	that variable, see the paragraphs about the cell output window above.

    Buttons :

      Clear graph
	  Clear the graph and remove all recording sites. If the recording
	  electrodes were visible in the cell output window, the cell output
	  window will be refreshed.

      Add plot
	  Use this button to add plot(s) to the graph.  This must be done
	  as no plots are preselected.  You can either click on the cell
	  to select or type a name in the dialog box.

      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.




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