/*----------------------------------------------------------------------------

	Detailed kinetic synapse mechanism
	----------------------------------

	Demo file to show the behavior of a synaptic currents mediated by
	glutamate NMDA receptors, using a detailed kinetic model of these
	receptors and a kinetic model for the release of transmitter.

	Kinetic model from Clements & Westbrook, Neuron 7: 605, 1991.


  See details in:

  Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  Kinetic models of 
  synaptic transmission.  In: Methods in Neuronal Modeling (2nd edition; 
  edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1998, pp. 1-25.

  (electronic copy available at http://cns.iaf.cnrs-gif.fr)


  Written by Alain Destexhe, Laval University, 1995

----------------------------------------------------------------------------*/



//----------------------------------------------------------------------------
//  load and define general graphical procedures
//----------------------------------------------------------------------------

// xopen("$(NEURONHOME)/lib/hoc/stdrun.hoc")

objectvar g[20]			// max 20 graphs
ngraph = 0

proc addgraph() { local ii	// define subroutine to add a new graph
				// addgraph("variable", minvalue, maxvalue)
	ngraph = ngraph+1
	ii = ngraph-1
	g[ii] = new Graph()
	g[ii].size(0,tstop,$2,$3)
	g[ii].xaxis()
	g[ii].yaxis()
	g[ii].addvar($s1,1,0)
	g[ii].save_name("graphList[0].")
	graphList[0].append(g[ii])
}

if(ismenu==0) {
  nrnmainmenu()			// create main menu
  nrncontrolmenu()		// crate control menu
  ismenu=1
}



//----------------------------------------------------------------------------
//  general parameters
//----------------------------------------------------------------------------

dt=0.025
tstop = 500
runStopAt = tstop
steps_per_ms = 1/dt
celsius = 36
v_init = -70



//----------------------------------------------------------------------------
//  create compartments and insert passive properties
//----------------------------------------------------------------------------

create PRE,POST
forall {
  diam=10
  L=10
  insert pas
  g_pas=1/5000
  e_pas=v_init
}



//----------------------------------------------------------------------------
//  insert presynaptic mechanisms
//----------------------------------------------------------------------------

access PRE		// insert Hodgk-Hux. Na+ and K+ currents for spikes

insert hh2
ek = -90
gnabar_hh2 = 0.1
gkbar_hh2 = 0.03


objectvar stim		// insert current injection
PRE stim = new IClamp(.5)
// note: for older versions of neuron, use PulseStim instead of IClamp
stim.del = 10
stim.dur = 2		// increase stim.dur to get a burst of presynaptic spikes
stim.amp = 0.1


insert caL		// HV Ca++ channel for transmitter release
p_caL=0.0002
q_caL=10
Ra_caL=1.6
Rb_caL=1.6


insert rel		// transmitter release
Ves_rel = 0.01		// conc of vesicles (mM)
Fmax_rel = 0.001 	// tot conc of proteins (F and V) (mM)
b_rel	= 1e16  	// rate cst for Ca++ binding to fusion factor
u_rel	= 0.1		// rate cst for Ca++ unbinding
k1_rel	= 1000		// rate cst for activation of vesicle
k2_rel	= 0.1		// rate cst for deactivation of vesicle
k3_rel	= 4		// rate cst for exocytosis
nt_rel	= 10000		// number of transmitter molecule per vesicle
kh_rel	= 10		// transmitter hydolysis constant

// cad is now part of rel mechanism
// insert cad		// Ca++ ATPase pump

kd_rel = 1e-5
kt_rel = 1e-3		// fast Ca++ removal
depth_rel = 1
taur_rel = 1e10



//----------------------------------------------------------------------------
//  insert postsynaptic mechansisms
//----------------------------------------------------------------------------

objectvar c
c = new NMDA5()			// create synapse
POST c.loc(0.5)				// assign postsynaptic compartment
setpointer c.C, PRE.T_rel(0.5)		// assign presynaptic compartment

Erev_NMDA5	= 0	//	(mV)	reversal potential (E_K)
mg_NMDA5	= 0	//	put in zero magnesium for the demo

// parameters from Hessler Shirke & Malinow 1993
Rb_NMDA5	= 5e-3    //	(/uM /ms)	: binding 		
Ru_NMDA5	= 12.9e-3  //	(/ms)	: unbinding		
Rd_NMDA5	= 8.4e-3   //	(/ms)	: desensitization
Rr_NMDA5	= 6.8e-3   //	(/ms)	: resensitization 
Ro_NMDA5	= 46.5e-3   //	(/ms)	: opening
Rc_NMDA5	= 73.8e-3   //	(/ms)	: closing
c.gmax 		= 50	//	(pS)	maximum conductance




//----------------------------------------------------------------------------
//  add graphs
//----------------------------------------------------------------------------


addgraph("PRE.v(0.5)",-90,40)
addgraph("PRE.T_rel(0.5)",0,1.5)

addgraph("c.i",-0.001,0.0001)
addgraph("POST.v(0.5)",v_init-2,v_init+4)