nmda.mod

TITLE minimal model of NMDA receptors

COMMENT
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	Minimal kinetic model for glutamate NMDA receptors
	==================================================

  Model of Destexhe, Mainen & Sejnowski, 1994:

	(closed) + T <-> (open)

  The simplest kinetics are considered for the binding of transmitter (T)
  to open postsynaptic receptors.   The corresponding equations are in
  similar form as the Hodgkin-Huxley model:

	dr/dt = alpha * [T] * (1-r) - beta * r

	I = gmax * [open] * B(V) * (V-Erev)

  where [T] is the transmitter concentration and r is the fraction of 
  receptors in the open form.  B(V) represents the voltage-dependent 
  Mg++ block (see Jahr & Stevens J Neurosci 10: 1830, 1990; Jahr & Stevens
  J Neurosci 10: 3178, 1990).

  If the time course of transmitter occurs as a pulse of fixed duration,
  then this first-order model can be solved analytically, leading to a very
  fast mechanism for simulating synaptic currents, since no differential
  equation must be solved (see Destexhe, Mainen & Sejnowski, 1994).

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  Based on voltage-clamp recordings of NMDA receptor-mediated currents in rat
  hippocampal slices (Hessler et al., Nature 366: 569-572, 1993), this model 
  was fit directly to experimental recordings in order to obtain the optimal
  values for the parameters (see Destexhe, Mainen and Sejnowski, 1996).

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  This mod file includes a mechanism to describe the time course of transmitter
  on the receptors.  The time course is approximated here as a brief pulse
  triggered when the presynaptic compartment produces an action potential.
  The pointer "pre" represents the voltage of the presynaptic compartment and
  must be connected to the appropriate variable in oc.

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  See details in:

  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.  Kinetic models of 
  synaptic transmission.  In: Methods in Neuronal Modeling (2nd edition; 
  edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1998, pp. 1-28.

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

  Written by Alain Destexhe, Laval University, 1995
  27-11-2002: the pulse is implemented using a counter, which is more
       stable numerically (thanks to Yann LeFranc)

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ENDCOMMENT



INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	POINT_PROCESS NMDA
	POINTER pre
	RANGE C, R, R0, R1, g, gmax, B, lastrelease, TimeCount
	NONSPECIFIC_CURRENT i
	GLOBAL Cmax, Cdur, Alpha, Beta, Erev, mg
	GLOBAL Prethresh, Deadtime, Rinf, Rtau
}
UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(umho) = (micromho)
	(mM) = (milli/liter)
}

PARAMETER {
	dt		(ms)
	Cmax	= 1	(mM)		: max transmitter concentration
	Cdur	= 1	(ms)		: transmitter duration (rising phase)
	Alpha	= 0.072	(/ms mM)	: forward (binding) rate
	Beta	= 0.0066 (/ms)		: backward (unbinding) rate
	Erev	= 0	(mV)		: reversal potential
	Prethresh = 0 			: voltage level nec for release
	Deadtime = 1	(ms)		: mimimum time between release events
	gmax		(umho)		: max conductance (100 pS single syn)
	mg	= 1    (mM)		: external magnesium concentration
}


ASSIGNED {
	v		(mV)		: postsynaptic voltage
	i 		(nA)		: current = g*(v - Erev)
	g 		(umho)		: conductance
	C		(mM)		: transmitter concentration
	R				: fraction of open channels
	R0				: open channels at start of release
	R1				: open channels at end of release
	Rinf				: steady state channels open
	Rtau		(ms)		: time constant of channel binding
	pre 				: pointer to presynaptic variable
	lastrelease	(ms)		: time of last spike
	B				: magnesium block
	TimeCount	(ms)		: time counter
}

INITIAL {
	R = 0
	C = 0
	Rinf = Cmax*Alpha / (Cmax*Alpha + Beta)
	Rtau = 1 / ((Alpha * Cmax) + Beta)
	lastrelease = -1000
	R1=0
	TimeCount=-1
}

BREAKPOINT {
	SOLVE release
	B = mgblock(v)		: B is the block by magnesium at this voltage
	g = gmax * R * B
	i = g*(v - Erev)
}

PROCEDURE release() {
	:will crash if user hasn't set pre with the connect statement 

	TimeCount=TimeCount-dt			: time since last release ended

						: ready for another release?
	if (TimeCount < -Deadtime) {
		if (pre > Prethresh) {		: spike occured?
			C = Cmax			: start new release
			R0 = R
			lastrelease = t
			TimeCount=Cdur
		}
						
	} else if (TimeCount > 0) {		: still releasing?
	
		: do nothing
	
	} else if (C == Cmax) {			: in dead time after release
		R1 = R
		C = 0.
	}



	if (C > 0) {				: transmitter being released?

	   R = Rinf + (R0 - Rinf) * exptable (- (t - lastrelease) / Rtau)
				
	} else {				: no release occuring

  	   R = R1 * exptable (- Beta * (t - (lastrelease + Cdur)))
	}

	VERBATIM
	return 0;
	ENDVERBATIM
}

FUNCTION exptable(x) { 
	TABLE  FROM -10 TO 10 WITH 2000

	if ((x > -10) && (x < 10)) {
		exptable = exp(x)
	} else {
		exptable = 0.
	}
}

FUNCTION mgblock(v(mV)) {
	TABLE 
	DEPEND mg
	FROM -140 TO 80 WITH 1000

	: from Jahr & Stevens

	mgblock = 1 / (1 + exp(0.062 (/mV) * -v) * (mg / 3.57 (mM)))
}