Channels
--------

Simulations that illustrates the application of simple kinetic models for 
the most current types of receptors: AMPA and NMDA glutamatergic, GABA-A
and GABA-B gabaergic.  These simulations are related to the following
book chapter- generates figures similar to fig 1.4 p19:

   Alain Destexhe, Zachary F. Mainen and Terrence J. Sejnowski
   Kinetic models of synaptic transmission
   In: Methods in Neuronal Modeling , 2nd Edition, 
   Edited by Koch, C. and Segev, I., MIT Press, Cambridge, MA, 1998, pp. 1-25. 

   These papers are related:

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  An efficient method for
   computing synaptic conductances based on a kinetic model of receptor binding
   Neural Computation 6: 10-14, 1994.

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Synthesis of models for
   excitable membranes, synaptic transmission and neuromodulation using a 
   common kinetic formalism, Journal of Computational Neuroscience 1: 
   195-230, 1994.

   (see postscript files synapse.ps.Z and markovSynapse.ps.Z)

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  Fast kinetic models for
   simulating AMPA, NMDA, GABA(A) and GABA(B) receptors.  In: Computation and
   Neural Systems, Vol. 4, Kluwer Academic Press, in press, 1995.

   (see postscript file cns94.ps.Z)


The present directory contains all the files needed to run the simulations
using the Interviews version of NEURON.  These files are commented and should
run straighforwardly, provided the NEURON simulator is installed properly.

The kinetic synapse mechanism

-----------------------------
This mechanisms has the following properties:

1. It is based on a simple kinetic scheme of binding of transmitter on
   postsynaptic receptors.  This description has the advantage that
   it is fully compatible with the level of description used for other
   mechanisms (Hodgkin-Huxley currents, calcium diffusion, etc).

2. The mechanism gives EPSP's or IPSP's from a pulse of transmitter.
   The waveform of these PSP's is very close to EPSP's or IPSP's measured
   experimentally, and the decay is monoexponential.  The user can set all
   the parameters corresponding to the rising phase, decay, amplitude, etc...
   (see .mod files)

3. Summation of consecutive PSP's is handled automatically by the 
   mechanism without need for an explicit event cue.  

4. Each synapse has a state variable corresponding to the fraction of 
   postsynaptic receptors in the open state.  However, the kinetics are
   first order, and so can be solved exactly.  This has the important
   advantage that it can be fit very easily to experimental recordings
   (see J. Computational Neurosci. paper).

5. Finally, this mechanism is very fast to compute. It does not require 
   solving any differential equations; at any given time only one exponential
   is calculated per synapse.  Thus, the mechanism is as fast to compute as 
   optimized versions of alpha function-based models.



How to run the simulation
-------------------------

This directory contains the files necessary to run a simulation of each
type of receptor mentioned above.  The parameters have been obtained
by fitting the model to whole-cell recordings of the various types of
synaptic response (see individual .oc and .mod files for details).

To compile the demo, NEURON and INTERVIEWS must be installed and working on
the machine you are using.  Just type "nrnivmodl" to compile the mechanisms
given in the mod files (glutamate.mod and gaba.mod are the mechanisms
for glutamate and gaba synapses, and HH.mod is the Hodgkin-Huxley kinetics). 

Then, execute one of the four example files by typing:

nrngui <ocfile>

where <ocfile> stands for either:

 	demo_ampa.oc	: AMPA/Kainate glutamatergic receptors
	demo_nmda.oc	: NMDA glutamatergic receptors
	demo_gabaa.oc	: GABA-A receptors
	demo_gabab.oc	: GABA-B receptors

Once the menu and graphics interface has appeared, click on "Init and Run"
button to start the simulation...



All these simulations were done using the NEURON simulator written by
Michael Hines, and which is available freely on internet via anonymous
ftp from neuron.neuro.duke.edu:/neuron.  For more information about how
to get NEURON and how to install it, please refer to the following sites:

  http://neuron.duke.edu/
  http://www.neuron.yale.edu/


For further information, please contact:

Alain Destexhe
CNRS, UNIC (Bat-33), 
Avenue de la Terrasse,
91198 Gif-sur-Yvette, 
France

email: Destexhe@iaf.cnrs-gif.fr
http://cns.iaf.cnrs-gif.fr

20071004 changed all synapse mod files so that they now use the
counter mechanism. -Destexhe.
20110411 changed solve method to cnexp in gabab.mod as per
"Integration methods for SOLVE statements" topic in the NEURON forum
http://www.neuron.yale.edu/phpBB/viewtopic.php?f=28&t=592
-ModelDB Administrator
20110412 corrected solve method to derivimplicit in gabab.mod (for
systems with kinetics)