COMMENT
Updated Exp2Syn synapse with Mg-blocked nmda channel.

Defaul values of parameters (time constants etc) set to match synaptic channels in 
striatal medium spiny neurons (Du et al., 2017; Chapman et al., 2003; Ding et al., 2008).

Robert . Lindroos @ ki . se

original comment:
________________
Two state kinetic scheme synapse described by rise time tau1,
and decay time constant tau2. The normalized peak condunductance is 1.
Decay time MUST be greater than rise time.

The solution of A->G->bath with rate constants 1/tau1 and 1/tau2 is
 A = a*exp(-t/tau1) and
 G = a*tau2/(tau2-tau1)*(-exp(-t/tau1) + exp(-t/tau2))
	where tau1 < tau2

If tau2-tau1 -> 0 then we have a alphasynapse.
and if tau1 -> 0 then we have just single exponential decay.

The factor is evaluated in the
initial block such that an event of weight 1 generates a
peak conductance of 1.

Because the solution is a sum of exponentials, the
coupled equations can be solved as a pair of independent equations
by the more efficient cnexp method.

ENDCOMMENT



NEURON {
	POINT_PROCESS adaptive_glutamate
	RANGE tau1_ampa, tau2_ampa, tau1_nmda, tau2_nmda
	RANGE erev_ampa, erev_nmda, g, i
	NONSPECIFIC_CURRENT i
	
	RANGE i_ampa, i_nmda, g_ampa, g_nmda, I, G, mg, q, alpha, eta, nmda_ca_fraction
	RANGE w0, NMDA_AMPA_ratio, wmax, wmin
	RANGE weight, last_dopamine, thresh_LTP, thresh_LTD
	RANGE learning_rate_w_LTP, learning_rate_w_LTD
	RANGE ca_nmdai_max, cali_max, active_syn_flag
	POINTER dopamine, stimulus_flag
	USEION ca_nmda READ ca_nmdai WRITE ica_nmda VALENCE 2	
	USEION cal READ cali VALENCE 2
}


UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(uS) = (microsiemens)
}


PARAMETER {
	erev_ampa        = 0.0       (mV)
	erev_nmda 	 = 15.0 (mV)
	tau1_ampa   = 1.9       (ms)
    	tau2_ampa   = 4.8       (ms)  : tau2 > tau1
    	tau1_nmda   = 5.52      (ms)  : old value was 5.63
    	tau2_nmda   = 231       (ms)  : tau2 > tau1
    
    	mg          = 1         (mM)
    	alpha       = 0.062
    	q           = 2
    	eta 	= 18
	NMDA_AMPA_ratio = 1
	w0 = 0.01
        wmax = 0.35
        wmin = 0.075

    	learning_rate_w_LTP = 0.01
	learning_rate_w_LTD = 0.01
        thresh_LTP = 0.15
        thresh_LTD = 0.015
        nmda_ca_fraction = 0.15
	ca_nmdai_max = 0
	cali_max = 0
	active_syn_flag = 1e-6
}


ASSIGNED {
	v (mV)
	i (nA)
	g (uS)
	factor_nmda
	factor_ampa
	i_ampa
	i_nmda
	g_ampa
	g_nmda
	block
	I
	G

	stimulus_flag
	dopamine
        last_dopamine
        ica_nmda (nA)
	ca_nmdai (mM)
	cali (mM)

	weight
}


STATE {
	A (uS)
	B (uS)
	C (uS)
	D (uS)
}



INITIAL {
	LOCAL tp
	if (tau1_nmda/tau2_nmda > .9999) {
		tau1_nmda = .9999*tau2_nmda
	}
	if (tau1_ampa/tau2_ampa > .9999) {
		tau1_ampa = .9999*tau2_ampa
	}
	
	: NMDA
	A           = 0
	B           = 0
	tp          = (tau1_nmda*tau2_nmda)/(tau2_nmda - tau1_nmda) * log(tau2_nmda/tau1_nmda)
	factor_nmda = -exp(-tp/tau1_nmda) + exp(-tp/tau2_nmda)
	factor_nmda = 1/factor_nmda
	
	: AMPA
	C           = 0
	D           = 0
	tp          = (tau1_ampa*tau2_ampa)/(tau2_ampa - tau1_ampa) * log(tau2_ampa/tau1_ampa)
	factor_ampa = -exp(-tp/tau1_ampa) + exp(-tp/tau2_ampa)
	factor_ampa = 1/factor_ampa
	
	weight = w0 
	active_syn_flag = 0
        last_dopamine = 0
}




BREAKPOINT {
	SOLVE state METHOD cnexp
	
	: NMDA
	g_nmda = (B - A)*weight*NMDA_AMPA_ratio
	block  = MgBlock()
	i_nmda = g_nmda * (v - erev_nmda) * block
	ica_nmda = nmda_ca_fraction*i_nmda
        i_nmda = (1 - nmda_ca_fraction)*i_nmda
	
	: AMPA
	g_ampa = (D - C)*weight
	i_ampa = g_ampa * (v - erev_ampa)
	
	: total current
	G = g_ampa + g_nmda
	I = i_ampa
        i = I

	if (stimulus_flag == 1) {
        	ca_nmdai_max = max(ca_nmdai, ca_nmdai_max)
        	cali_max = max(cali, cali_max)
		last_dopamine = dopamine
        } else {
	  if (last_dopamine == 1 && active_syn_flag == 1) {

		  weight = weight + learning_rate_w_LTP * pind_LTP(ca_nmdai)*(wmax-weight)
		  
          } else if (last_dopamine == -1 && active_syn_flag == 1) {

		  weight = weight - learning_rate_w_LTD * pind_LTD(cali)*(weight - wmin)
		  
          }
          last_dopamine = dopamine		
          reset_max()
        }
}



DERIVATIVE state {
	A' = -A/tau1_nmda*q
	B' = -B/tau2_nmda*q
	C' = -C/tau1_ampa
	D' = -D/tau2_ampa
}



NET_RECEIVE(dummy (uS)) {
	active_syn_flag = 1
	
	A = A + factor_nmda
	B = B + factor_nmda
	C = C + factor_ampa
	D = D + factor_ampa
}


FUNCTION MgBlock() {
    
    MgBlock = 1 / (1 + mg * eta * exp(-alpha * v)  )
    
}

FUNCTION pind_LTP(conc) {
    if (conc > thresh_LTP) {
	pind_LTP = 1
    } else {
	pind_LTP = 0
    }
}

FUNCTION pind_LTD(conc) {
    if (conc > thresh_LTD) {
	pind_LTD = 1
    } else {
	pind_LTD = 0
    }
}


FUNCTION reset_max() {
	ca_nmdai_max = 0
        cali_max = 0
	active_syn_flag = 0
}

FUNCTION max(current, maximum) {
   if (current>maximum) { 
      max = current
   } else {
      max = maximum
   }
}

FUNCTION min(current, minimum) {
   if (current<minimum) { 
      min = current
   } else {
      min = minimum
   }
}