Rhesus Monkey Layer 3 Pyramidal Neurons: Young vs aged PFC (Coskren et al. 2015)

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Accession:168858
Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. Tuning passive parameters for each model predicted significantly higher membrane resistance (Rm) in aged versus young neurons. This Rm increase alone did not account for the empirically observed fI-curves, but coupling these Rm values with subtle differences in morphology and membrane capacitance Cm did. The predicted differences in passive parameters (or other parameters with similar effects) are mathematically plausible, but must be tested empirically.
Reference:
1 . Coskren PJ, Luebke JI, Kabaso D, Wearne SL, Yadav A, Rumbell T, Hof PR, Weaver CM (2015) Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. J Comput Neurosci 38:263-83 [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): Neocortex L2/3 pyramidal GLU cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Influence of Dendritic Geometry; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s;
Implementer(s): Weaver, Christina [christina.weaver at fandm.edu];
Search NeuronDB for information about:  Neocortex L2/3 pyramidal GLU cell; I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
/
CoskrenEtAl2015
HHmodel
models
README.html
cad.mod *
cal.mod
cat.mod
hcurrent.mod
k2.mod
ka.mod
kahp.mod *
kc.mod
kdr.mod
km.mod
kvz_nature.mod *
mar.mod
max.mod
naf.mod
nap.mod
naz_nature.mod *
origlen.mod *
pass_wRel.mod
peak.mod *
shunt.mod
skahp.mod
Voffset.mod
vsource.mod *
aniruddha_young10axon.hoc
coskren_make_gui.hoc
fixnseg.hoc
init.hoc
linear_conductances_traub.hoc
main_CoskrenEtAl_extTraub.hoc
make_gui.hoc
make_gui2.hoc
mosinit.hoc
readcell_nomechanisms.hoc
scaleRm_aug3f.hoc
screenshot.png
Vkeep.ses
                            
/*****************************************************************************

    This file contains functions implementing a linear distribution 
    of channel conductances.

    Christina Weaver
    Feb 2006
    last updated Jun '07

NOTE:  NEURON does not consider the values 0 and 1 to be separate nodes.  
       Instead, the values of any range variables at those points is 
       equal to the value assumed at the nearest node.  As a result 
       there will be a slight discontinuity of the linear variation 
       of the range variables at section ends.  To minimize this 
       discontinuity you can increase NSEG in all the sections, but be 
       warned that this could cause your simulations to run much more 
       slowly.


    Procedures defined below include:

    applysec_slope()	After the appropriate slope and intercept have 
			been determined for this particular section, 
			apply the linear function to the desired range 
			variable.	
    assign_slope2all()	Write a matlab file that determines the appropriate 
			conductance parameters throughout the dendrite, to 
			apply the specified global conductance slope and 
			intercept to the entire dendrite.  No parameter 
			values are actually changed in this procedure.
    BParea()		Calculate the area between the backpropagation 
			curve and the straight line V = minV (default -80).  
			This is measured in each segment as the maximum 
			voltage observed over the entire simulation.
    calc_global_slope()	Given the conductance values of the proximal and 
			distal dendritic sections, calculate the appropriate 
			slope from these values and the length of the 
			dendrite.
    findsec_slope()	Determine the appropriate slope and intercept 
			for this section, and apply the linear change to 
			the section.
    linear_bakerKCAdec_ratios()    Apply the conductance ratios referred 
				   to as "bakerKCAdec" linearly throughout 
				   the dendrite.
    print_cond_linscale()    Print the conductance values with distance 
			     for all neuron compartments.
    set_cond_linear()   Apply this global slope and intercept to the 
			specified conductance type, for all dendritic 
			segments.
    total_dend_cond()	Calculate the total amount of conductance of the 
			specified channel type.  That is, multiply g_bar * 
			surface area of each dendritic section.


*****************************************************************************/

objref fin
VERBOSE = 0
most_distal = 0
most_proximal = 0

/******************************************************************

    applysec_slope()

    After the appropriate slope and intercept have been determined 
    for this particular section, apply the linear function to the 
    desired range variable.  If the proposed conductance value is 
    negative, it is instead set to zero.

    input	$s1	section name
		$2	slope
		$3	intercept
		$4	index of range variable

    0 : gbar_naf
    1 : gbar_kdr
    2 : gbar_kc
    3 : phi_cad		// not a range variable (phi equivalent to Kp_cad from Av-Ron)
    4 : beta_cad		// not a range variable (beta equivalent to RCa_cad from Av-Ron)
    5 : gbar_ka
    6 : gbar_cal
    7 : gbar_nap
    8 : g_pas
    9 : gbar_cat
   10 : gbar_km
   11 : gbar_k2
   12 : gbar_kahp
   13 : gbar_h

******************************************************************/
proc applysec_slope() { local m, y0, idx

    m   = $2
    y0  = $3
    idx = $4

    forsec $s1 {
        for(x) {

            // if we execute this command on x==1
            //if( x == 1 ) continue

	    if( idx == 0 && ismembrane("naf") ) {
                gbar_naf(x) = m*x + y0
                if( gbar_naf(x) < 0 ) gbar_naf(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_naf(%g) = %g\n",x,gbar_naf(x))
		continue		
	    }
	    if( idx == 1 && ismembrane("kdr") ) {
                gbar_kdr(x) = m*x + y0
                if( gbar_kdr(x) < 0 ) gbar_kdr(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_kdr(%g) = %g\n",x,gbar_kdr(x))
		continue		
	    }
	    if( idx == 2 && ismembrane("kc") ) {
                gbar_kc(x) = m*x + y0
                if( gbar_kc(x) < 0 ) gbar_kc(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_kc(%g) = %g\n",x,gbar_kc(x))
		continue		
	    }

	    // phi & beta (i.e. Avron's Kp and Rca) are not range variables; skip over idx == 3 or 4

	    if( idx == 5 && ismembrane("ka") ) {
                gbar_ka(x) = m*x + y0
                if( gbar_ka(x) < 0 ) gbar_ka(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_ka(%g) = %g\n",x,gbar_ka(x))
		continue		
	    }
	    if( idx == 6 && ismembrane("cal") ) {
                gbar_cal(x) = m*x + y0
                if( gbar_cal(x) < 0 ) gbar_cal(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_cal(%g) = %g\n",x,gbar_cal(x))
		continue		
	    }
	    if( idx == 7 && ismembrane("nap") ) {
                gbar_nap(x) = m*x + y0
                if( gbar_nap(x) < 0 ) gbar_nap(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_nap(%g) = %g\n",x,gbar_nap(x))
		continue		
	    }
	    if( idx == 8 && ismembrane("pas") ) {
                g_pas(x) = m*x + y0
                if( g_pas(x) < 0 ) g_pas(x) = 0
		if( VERBOSE ) printf("\t\tSetting g_pas(%g) = %g\n",x,g_pas(x))
		continue		
	    } else {
 	        if( idx == 8 && ismembrane("pasR") ) {
                    g_pasR(x) = m*x + y0
                    if( g_pasR(x) < 0 ) g_pasR(x) = 0
		    if( VERBOSE ) printf("\t\tSetting g_pasR(%g) = %g\n",x,g_pasR(x))
		    continue		
                }
	    }
	    if( idx == 9 && ismembrane("cat") ) {
                gbar_cat(x) = m*x + y0
                if( gbar_cat(x) < 0 ) gbar_cat(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_cat(%g) = %g\n",x,gbar_cat(x))
		continue		
	    }
	    if( idx == 10 && ismembrane("km") ) {
                gbar_km(x) = m*x + y0
                if( gbar_km(x) < 0 ) gbar_km(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_km(%g) = %g\n",x,gbar_km(x))
		continue		
	    }
	    if( idx == 11 && ismembrane("k2") ) {
                gbar_k2(x) = m*x + y0
                if( gbar_k2(x) < 0 ) gbar_k2(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_k2(%g) = %g\n",x,gbar_k2(x))
		continue		
	    }
	    if( idx == 12 && ismembrane("kahp") ) {
                gbar_kahp(x) = m*x + y0
                if( gbar_kahp(x) < 0 ) gbar_kahp(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_kahp(%g) = %g\n",x,gbar_kahp(x))
		continue		
	    }
	    if( idx == 13 && ismembrane("ar") ) {
                gbar_ar(x) = m*x + y0
                if( gbar_ar(x) < 0 ) gbar_ar(x) = 0
		if( VERBOSE ) printf("\t\tSetting gbar_ar(%g) = %g\n",x,gbar_ar(x))
		continue		
	    }
        }
    }
}

/******************************************************************

    calc_global_slope()

    Given the conductance values of the proximal and distal dendritic 
    sections, calculate the appropriate slope from these values and 
    the length of the dendrite.

    input	$1	proximal conductance value (distance = 0)
                $2	most distal conductance value (distance = 
			end of dendrite)

******************************************************************/
func calc_global_slope() {  local s_rad, chgC, chgD, Pdist, Ddist, slp, segID

    soma { 
        distance() 
        Pdist = distance(1)
	if( VERBOSE ) printf("Proximal distance set to %g\n",Pdist)
    }

    strdef lng_name
    Ddist = find_longest_dend(lng_name,segID)

    chgD = Ddist - Pdist
    chgC = $2 - $1

    slp = chgC / chgD

    return slp


}


/******************************************************************

    calc_global_slopefac()

    Given the values of the proximal and distal dendritic 
    sections relative to the soma (e.g. '2' for twice the soma value), 
    calculate the appropriate factor to apply to each compartment's 
    maximal conductances.

    Let the value of a certain conductance in the soma be g0.  Suppose that conductance
    at the most proximal dendritic segments (distance x0) is defined by k0 * g0, and k1 * g0
    at the most distal segments (distance x1).

    Then if dendritic conductances are to be scaled linearly, they will be
    defined by    y1 - y0 = m * (x1-x0)		i.e.

		  (k1-k0) * g0 
                  -------	= m
                  (x1-x0)

    Then for any dendritic point at a distance x*, the appropriate conductance to apply is:

        y* - y0 = m * (x* - x0); suppose y = k* * g0.  Then

             (k1-k0) 
        k* = ------- * (x* - x0) + k0
             (x1-x0)

    The values k0 are stored in int_vec;  store the value of the first term (the 'slope scale factor')
    in slp_vec.  The values k1 are stored in sec_vec, defined in linear_migliore_ratios() below.


    input	$o1	vector of proximal conductances, relative to soma value(distance = 0) (int_vec)
                $o2	vector of most distal conductance, relative to soma value (distance = 
			end of dendrite) (sec_vec)
                $o3	vector of slope factors, slp_vec

******************************************************************/
proc calc_global_slopefac() {  local s_rad, chgC, chgD, Pdist, Ddist, slp, segID, i

    soma { 
        distance() 
    }

    strdef lng_name, shrt_name
    Ddist = find_longest_dend(lng_name,segID)
    most_distal = Ddist
    Pdist = find_shortest_dend(shrt_name,segID)
    most_proximal = Pdist

    chgD = Ddist - Pdist

    $o3 = new Vector()
    for i = 0, $o1.size()-1 {
        chgC = $o2.x[i]-$o1.x[i]
        slp  = chgC / chgD
        $o3.append(slp)
    }

/***
printf("Finished calc_global_slopefac.  Given dendrites from %g to %g;\nint_vec = \n",most_proximal,most_distal)
$o1.printf
printf(" and sec_vec\n")
$o2.printf
printf("\nWe find slp_vec=\n")
$o3.printf
***/

}


/******************************************************************

    findsec_slope()

    Determine the appropriate slope and intercept for this section, 
    and apply the linear change to the section.

    input	$s1	section name
		$2	global slope
		$3	global intercept
                $4	index of conductance type to change

******************************************************************/
proc findsec_slope() { local m, g0, y0, y1, m_lcl

    soma { 
        distance() 
        s_end = distance(.5)
    }
    

    m = $2
    g0 = $3

    forsec $s1 {
        y0 = g0 + m*(distance(0)-s_end)
        y1 = g0 + m*(distance(1)-s_end)
        m_lcl = y1-y0

        if( VERBOSE) {
            printf("For section %s with Length %g and distance from soma %g,\n",secname(),L,distance(0)-s_end)
            printf("\tGlobal slope %g, intcpt %g becomes local slope %g, local intcpt %g\n",m,g0,m_lcl,y0)
        }
        applysec_slope($s1,m_lcl,y0,$4)
    }
}


/*******************************************************************

    set_cond_linear()

    Apply this global slope and intercept to the specified conductance 
    type, for all dendritic segments.

    input	$1	index of conductance type (see applysec_slope 
			for list)
		$2	global slope to apply
		$3	intercept value for the most proximal dendrite 
			section

*******************************************************************/
proc set_cond_linear() {

    forsec dendritic {
	ifsec "soma" continue

        findsec_slope(secname(),$2,$3,$1)
    }
    copy_slope_intercept($1,$2,$3)
}


/********************************************************************

    assign_slope2all()
  
    Write a matlab file that determines the appropriate conductance 
    parameters throughout the dendrite, to apply the specified global 
    conductance slope and intercept to the entire dendrite.  No 
    parameter values are actually changed in this procedure.

    input	$1	global slope
		$2	global intercept
		$s3	file basename for output

********************************************************************/
proc assign_slope2all() { local i, s_rad

    soma { 
        distance() 
        s_rad = distance(1)
    }

    strdef finname

    sprint(finname,"checklin_%s.m",$s3)
    fin = new File()
    fin.wopen(finname)

    //findsec_slope("dend[0]",$1,$2)
    //findsec_slope("dend[1]",$1,$2)
    //findsec_slope("dend[2]",$1,$2)

    forsec dendritic {
        fin.printf("%s = [ \n",secname())
            for(x) {
                if( ismembrane("pas")) { 
                    fin.printf("%g %g %g\n",x,distance(x)-s_rad,g_pas(x))
                } else {
                    if( ismembrane("pasR")) { 
                        fin.printf("%g %g %g\n",x,distance(x)-s_rad,g_pasR(x))
                    }
                }
	    }
        fin.printf("];\n")
    }

    /***
    fin.printf("plot(dend0(:,2),dend0(:,3),dend1(:,2),dend1(:,3),dend2(:,2),dend2(:,3));\n")
    fin.printf("legend('dend[0]','dend[1]','dend[2]');\n")
    fin.printf("m = %g; intcpt = %g;\n",$1,$2)
    fin.printf("ttl = sprintf('Changing g_{pas}:  Slope %%g, intercept %%g',m,intcpt);\n")
    fin.printf("title(ttl);\n")
    ***/

    fin.close()
}



/********************************************************************

    print_cond_linscale()
  
    Print the conductance values with distance for all neuron compartments.

    input	$1	index of conductance type
                $s2	if writing M-file, suffix for parameter

********************************************************************/
proc print_cond_linscale() { local idx, cval, i, tot

    strdef strg, lgstrg

    idx = $1 
    if( idx == 0 )  {
	printf("Values of g_Na:\n")
        strg = "Na"
    }
    if( idx == 1 )  {
	printf("Values of g_KDR:\n")
	strg = "KDR"
    }
    if( idx == 2 )  {
	printf("Values of g_KCa:\n")
	strg = "KCa"
    }
    if( idx == 3 )  {
	printf("Values of Kp (Ca influx):\n")
	strg = "Kp"
    }
    if( idx == 4 )  {
	printf("Values of beta (Ca efflux):\n")
	strg = "beta"
    }
    if( idx == 5 )  {
	printf("Values of g_KA:\n")
    	strg = "KA"
    }

    if( idx == 6 )  {
	printf("Values of g_CaL:\n")
	strg = "Ca"
    }
    if( idx == 7 )  {
	printf("Values of g_NaP:\n")
	strg = "NaP"
    }
    if( idx == 8 )  {
	printf("Values of g_Leak:\n")
	strg = "Lk"
    }
    if( idx == 9 )  {
	printf("Values of gbar_caT:\n")
	strg = "CaT"
    }

    soma { 
        distance() 
        s_rad = distance(1)
    }

    forall {
        print secname(), nseg, " segments"
	for(x) {
            cval = -1 
	    if( idx == 0 && ismembrane("naf") ) cval = gbar_naf(x) 
	    if( idx == 1 && ismembrane("kdr") ) cval = gbar_kdr(x) 
	    if( idx == 2 && ismembrane("kc") ) cval = gbar_kc(x) 

	    // Kp and beta are not range variables; skip over idx == 3 or 4

	    if( idx == 5 && ismembrane("ka") ) cval = gbar_ka(x) 
	    if( idx == 6 && ismembrane("cal") ) cval = gbar_cal(x) 
	    if( idx == 7 && ismembrane("nap") ) cval = gbar_nap(x) 
	    if( idx == 8 && ismembrane("pas") ) cval = g_pas(x) 
	    if( idx == 8 && ismembrane("pasR") ) cval = g_pasR(x) 
	    if( idx == 9 && ismembrane("cat") ) cval = gbar_cat(x) 
	    if( idx == 10 && ismembrane("k2") ) cval = gbar_k2(x) 
	    if( idx == 11 && ismembrane("km") ) cval = gbar_km(x) 
	    if( idx == 12 && ismembrane("kahp") ) cval = gbar_kahp(x) 
	    if( idx == 13 && ismembrane("ar") ) cval = gbar_ar(x) 

	    printf("\t[%g]\t%g um\t%g\n",x,distance(x),cval)

	}

    }
   tot = total_dend_cond(idx,$s2)


}



/********************************************************************

    print_lincond_smry()
  
    Print the conductance values with distance for all neuron compartments.

    input	$1	index of conductance type

********************************************************************/
proc print_lincond_smry() { local idx, cval, i, tot

    strdef strg, lgstrg

    for idx = 0, 8 {
        cval = -1

	if( idx == 0 )  { strg = "Na" }
    if( idx == 1 )  {
	strg = "KDR"
    }
    if( idx == 2 )  {
	strg = "KCa"
    }
    if( idx == 3 )  {
	strg = "Kp"
    }
    if( idx == 4 )  {
	strg = "beta"
    }
    if( idx == 5 )  {
    	strg = "KA"
    }

    if( idx == 6 )  {
	strg = "Ca"
    }
    if( idx == 7 )  {
	strg = "NaP"
    }
    if( idx == 8 )  {
	strg = "Lk"
    }

	    if( idx == 0 && ismembrane("naf") ) cval = dendritic.object(0).gbar_naf(0) / soma.gbar_naf
	    if( idx == 1 && ismembrane("kdr") ) cval = dendritic.object(0).gbar_kdr(0) / soma.gbar_kdr 
	    if( idx == 2 && ismembrane("kc") ) cval = dendritic.object(0).gbar_kc(0)  / soma.gbar_kc

	    // phi and beta are not range variables; skip over idx == 3 or 4
        if( idx == 3 && ismembrane("cad") ) cval = phi_cad
        if( idx == 4 && ismembrane("cad") ) cval = beta_cad

	    if( idx == 5 && ismembrane("ka") ) cval = dendritic.object(0).gbar_ka(0)   / soma.gbar_ka
	    if( idx == 6 && ismembrane("cal") ) cval = dendritic.object(0).gbar_cal(0)   / soma.gbar_cal
	    if( idx == 7 && ismembrane("nap") ) cval = dendritic.object(0).gbar_nap(0)   / soma.gbar_nap
	    if( idx == 8 && ismembrane("pas") ) cval = dendritic.object(0).g_pas(0)   / soma.g_pas
	    if( idx == 8 && ismembrane("pasR") ) cval = dendritic.object(0).g_pasR(0)   / soma.g_pasR
	    if( idx == 9 && ismembrane("cat") ) cval = dendritic.object(0).gbar_cat(0)   / soma.gbar_cat
	    if( idx == 10 && ismembrane("k2") ) cval = dendritic.object(0).gbar_k2(0)   / soma.gbar_k2
	    if( idx == 11 && ismembrane("km") ) cval = dendritic.object(0).gbar_km(0)   / soma.gbar_km
	    if( idx == 12 && ismembrane("kahp") ) cval = dendritic.object(0).gbar_kahp(0)   / soma.gbar_kahp
	    if( idx == 13 && ismembrane("ar") ) cval = dendritic.object(0).gbar_ar(0)   / soma.gbar_ar

	    printf("%s: %g\n",strg,cval)

    }

}


/*********************************************************************

    BParea()

    Calculate the area between the backpropagation curve and the 
    straight line V = minV (default -80).  This is 
    measured in each segment as the maximum voltage observed over 
    the entire simulation.

*********************************************************************/
func BParea() { local sum, minV

    sum = 0
    minV = -80

    forsec dendritic {

        if( !ismembrane("mar")) continue 
	if( VERBOSE ) print secname()
        for(x) {
            if( x==0 || x==1 ) continue
            sum += L*(val_mar(x)-minV)/(nseg)
	    if( VERBOSE ) print "\t",x,nseg,L/(nseg),val_mar(x),sum
        }
    }

    return sum
}


/*********************************************************************

    total_dend_cond()

    Calculate the total amount of conductance of the specified channel 
    type.  That is, multiply g_bar * surface area of each dendritic 
    section.


    input	$1	index of conductance type
		$s2	channel suffix (e.g. "kdr" for gbar_kdr)

*********************************************************************/
func total_dend_cond() { local sum, minV, idx

strdef strg 

    idx = $1
    sum = 0

    forsec dendritic {

        if( !ismembrane($s2)) continue 
        print secname()
        for(x) {
            if( x==0 || x==1 ) continue
            cval = -1 
	    if( idx == 0 && ismembrane("naf") ) cval = gbar_naf(x) 
	    if( idx == 1 && ismembrane("kdr") ) cval = gbar_kdr(x) 
	    if( idx == 2 && ismembrane("kc") ) cval = gbar_kc(x) 

	    // phi and beta are not range variables; skip over idx == 3 or 4

	    if( idx == 5 && ismembrane("ka") ) cval = gbar_ka(x) 
	    if( idx == 6 && ismembrane("cal") ) cval = gbar_cal(x) 
	    if( idx == 7 && ismembrane("nap") ) cval = gbar_nap(x) 
	    if( idx == 8 && ismembrane("pas") ) cval = g_pas(x) 
	    if( idx == 8 && ismembrane("pasR") ) cval = g_pasR(x) 
	    if( idx == 9 && ismembrane("cat") ) cval = gbar_cat(x) 
	    if( idx == 10 && ismembrane("k2") ) cval = gbar_k2(x) 
	    if( idx == 11 && ismembrane("km") ) cval = gbar_km(x) 
	    if( idx == 12 && ismembrane("kahp") ) cval = gbar_kahp(x) 
	    if( idx == 13 && ismembrane("ar") ) cval = gbar_ar(x) 

	    if( cval < 0 ) continue

            sum += cval*area(x)
	    printf("\t%g:\t%g * %g = %g\n",x,cval,area(x),cval*area(x))
        }
    }

    if( idx == 0 )  strg = "Na"
    if( idx == 1 )  strg = "KDR"
    if( idx == 2 )  strg = "KCa"
    if( idx == 3 )  strg = "phi"
    if( idx == 4 )  strg = "beta"
    if( idx == 5 )  strg = "KA"
    if( idx == 6 )  strg = "CaL"
    if( idx == 7 )  strg = "NaP"
    if( idx == 8 )  strg = "Leak"
    if( idx == 9 )  strg = "CaT"
    if( idx == 10 )  strg = "K2"
    if( idx == 11 )  strg = "KM"
    if( idx == 12 )  strg = "KAHP"
    if( idx == 13 )  strg = "AR"

    printf("Total %s conductance = %g mS\n",strg,sum)

    return sum
}

// these vectors store the dendritic conductance info:  slopes & intercepts.
objref slp_vec, int_vec, sec_vec
slp_vec = new Vector()
int_vec = new Vector()
sec_vec = new Vector()


/********************************************************************

    copy_slope_intercept

    We've just applied the global slope & intercept to the dendrite. 
    Now copy that information into the 'slp_vec' and 'int_vec' 
    vectors.

    input	$1	index of conductance type (see applysec_slope 
			for list)
		$2	global slope that was applied
		$3	intercept value for the most proximal dendrite 
			section

********************************************************************/
proc copy_slope_intercept() {

    if( $1 <= 2 ) {
        slp_vec.x[$1] = $2
        int_vec.x[$1] = $3
        if( VERBOSE ) printf("index %d -> slope, int [%d] = %g, %g\n",$1,$1,slp_vec.x[$1],int_vec.x[$1])
    } else {
        if( $1 > 4 && $1 < 9 ) {
            slp_vec.x[$1-2] = $2
            int_vec.x[$1-2] = $3
            if( VERBOSE ) printf("index %d -> slope, int [%d] = %g, %g\n",$1,$1-2,slp_vec.x[$1-2],int_vec.x[$1-2])
        } else {
            if( VERBOSE ) printf("index %d NOT APPLICABLE for slope/intercept vector.\n",$1)
        }
    }
}


/******************************************************************

    define_dend_slope()

    Given the proximal and distal dendritic values, apply the associated linearly scaled conductance.

    input	$1	index:  which conductance to change?

    if( idx == 0 )  strg = "Na"
    if( idx == 1 )  strg = "KDR"
    if( idx == 2 )  strg = "KCa"
    if( idx == 3 )  strg = "phi"
    if( idx == 4 )  strg = "beta"
    if( idx == 5 )  strg = "KA"
    if( idx == 6 )  strg = "CaL"
    if( idx == 7 )  strg = "NaP"
    if( idx == 8 )  strg = "Leak"

		$2	proximal conductance value
		$3	distal conductance 

******************************************************************/
proc define_dend_slope() { local slp, idx, Pval, Dval

    idx  = $1
    Pval = $2
    Dval = $3

    	slp = calc_global_slope(Pval,Dval)
    	set_cond_linear(idx,slp,Pval)
    	//print_cond_linscale(idx,"L","")
    	//printf("\n\n")

}



/******************************************************************

    linear_migliore_ratios()

    Jun 11 '07

    Based on data found in Migliore & Shepherd '02 review, plus a 
    few other references on neocortical pyramidal cells (mostly layer 5).

******************************************************************/
proc linear_migliore_ratios() { local slp, idx, Pval, Dval

    int_vec = new Vector()
    sec_vec = new Vector()

    // component 0 of int_vec and sec_vec
    pri_nafac = 1
    sec_nafac = $2
    int_vec.append(pri_nafac)
    sec_vec.append(sec_nafac)

    pri_kfac = 1
    sec_kfac = $3
    int_vec.append(pri_kfac)
    sec_vec.append(sec_kfac)

    pri_kcafac = 1
    sec_kcafac = 1
    int_vec.append(pri_kcafac)
    sec_vec.append(sec_kcafac)

    // append for phi_cad and beta_cad, in case we need it later.
    int_vec.append(0)
    sec_vec.append(0)
    int_vec.append(0)
    sec_vec.append(0)

    // component 5 of int_vec and sec_vec
    pri_kafac = 1
    sec_kafac = 2
    int_vec.append(pri_kafac)
    sec_vec.append(sec_kafac)

    pri_cafac = 1
    sec_cafac = 1
    int_vec.append(pri_cafac)
    sec_vec.append(sec_cafac)

    pri_napfac = pri_nafac
    sec_napfac = sec_nafac
    int_vec.append(pri_napfac)
    sec_vec.append(sec_napfac)

    pri_pasfac = 1
    sec_pasfac = 1
    int_vec.append(pri_pasfac)
    sec_vec.append(sec_pasfac)

    // component 9 of int_vec and sec_vec
    pri_locafac = 1
    sec_locafac = 1 
    int_vec.append(pri_locafac)
    sec_vec.append(sec_locafac)

    pri_k2fac = 1
    sec_k2fac = 1 
    int_vec.append(pri_k2fac)
    sec_vec.append(sec_k2fac)

    pri_kmfac = 1
    sec_kmfac = 1 
    int_vec.append(pri_kmfac)
    sec_vec.append(sec_kmfac)

    pri_kahpfac = 1
    sec_kahpfac = 1 
    int_vec.append(pri_kahpfac)
    sec_vec.append(sec_kahpfac)

    // component 13 of int_vec and sec_vec
    pri_hfac = 1
    sec_hfac = $1 
    int_vec.append(pri_hfac)
    sec_vec.append(sec_hfac)

    pri_skahpfac = 1
    sec_skahpfac = 1
    int_vec.append(pri_skahpfac)
    sec_vec.append(sec_skahpfac)

//printf("From linear_migliore_ratios()\n")
    calc_global_slopefac(int_vec,sec_vec,slp_vec)
    apply_linear_ratios()
}


/*****************************************************************

    apply_one_dendcond()

    input	$1	index of channel to set
		$2	conductance value in the soma

    Use data contained in int_vec and slp_vec (see calc_global_slopevec)
    to set the conductance value throughout the dendrites.

*****************************************************************/
proc apply_one_dendcond() { local distx, idx

    strdef tg

    idx = $1
    forsec dendritic {
        for(x) {
            distx = distance(x)

            kstar = slp_vec.x[idx] * (distx - most_proximal) + int_vec.x[idx]

                if( idx == 0 && ismembrane("naf") ) {
                    tg = "Na"
                    gbar_naf(x) = $2 * kstar
                }
                if( idx == 1 && ismembrane("kdr") ) {
                    tg = "KDR"
                    gbar_kdr(x) = $2 * kstar
                }
                if( idx == 2 && ismembrane("kc") ) {
                    tg = "KCa"
                    gbar_kc(x) = $2 * kstar
                }
                if( idx == 5 && ismembrane("ka") ) {
                    tg = "KA"
                    gbar_ka(x) = $2 * kstar
                }
                if( idx == 6 && ismembrane("cal") ) {
                    tg = "CaL"
                    gbar_cal(x) = $2 * kstar
                }
                if( idx == 7 && ismembrane("nap") ) {
                    tg = "NaP"
                    gbar_nap(x) = $2 * kstar
                }
                if( idx == 8 && ismembrane("pas") ) {
                    tg = "Pas"
                    g_pas(x) = $2 * kstar
                }
                if( idx == 8 && ismembrane("pasR") ) {
                    tg = "PasR"
                    g_pasR(x) = $2 * kstar
                }
               if( idx == 9 && ismembrane("cat") ) {
                    tg = "CaT"
                    gbar_cat(x) = $2 * kstar
                }
                if( idx == 10 && ismembrane("k2") ) {
                    tg = "K2"
                    gbar_k2(x) = $2 * kstar
                }
                if( idx == 11 && ismembrane("km") ) {
                    tg = "KM"
                    gbar_km(x) = $2 * kstar
                }
                if( idx == 12 && ismembrane("kahp") ) {
                    tg = "KAHP"
                    gbar_kahp(x) = $2 * kstar
                }
                if( idx == 13 && ismembrane("ar") ) {
                    tg = "H"
                    gbar_ar(x) = $2 * kstar
                }
                if( idx == 14 && ismembrane("skahp") ) {
                    tg = "SKAHP"
                    gbar_skahp(x) = $2 * kstar
                }
	        if( VERBOSE && idx == 5 ) {  
	            printf("%s, [%g\t%g]:  %s:  gbar %g * kstar %g = %g\n",secname(),x,distx,tg,$2,kstar,$2*kstar)
        	}

            }
        }
        forsec axon {
	    if( ismembrane("kc")) gbar_kc=0 
	    if( ismembrane("skahp"))  gbar_skahp=0 
	    if( ismembrane("kahp"))   gbar_kahp=0 
	    if( ismembrane("cal"))    gbar_cal=0 
	    if( ismembrane("ar"))     gbar_ar=0 
	    if( ismembrane("cat"))    gbar_cat=0 
	    if( ismembrane("km"))     gbar_km=0
	}
        forsec "AxonInitseg" {
	    if( ismembrane("kc")) gbar_kc=0 
	    if( ismembrane("skahp"))  gbar_skahp=0 
	    if( ismembrane("kahp"))   gbar_kahp=0 
	    if( ismembrane("cal"))    gbar_cal=0 
	    if( ismembrane("ar"))     gbar_ar=0 
	    if( ismembrane("cat"))    gbar_cat=0 
	    if( ismembrane("km"))     gbar_km=0
	}

}


/*****************************************************************

    apply_linear_ratios()

    Assuming pri*fac and sec*fac have been calculated according 
    to some prior rule, apply these as the proximal and distal 
    values of the dendritic conductances.  Intermediate distances 
    along the dendrite have conductances that vary linearly between 
    these two values.

*****************************************************************/
proc apply_linear_ratios() {  local idx, g0

    strdef tg

    soma{ distance() }

    for idx = 0, int_vec.size()-1 {

        if( idx == 0 ) g0 = soma.gbar_naf
        if( idx == 1 ) g0 = soma.gbar_kdr
        if( idx == 2 ) g0 = soma.gbar_kc

        if( idx == 3 || idx == 4 ) continue

        if( idx == 5 ) g0 = soma.gbar_ka
        if( idx == 6 ) g0 = soma.gbar_cal
        if( idx == 7 ) g0 = soma.gbar_nap
        if( idx == 8 && ismembrane("pas" ) ) g0 = soma.g_pas
        if( idx == 8 && ismembrane("pasR") ) g0 = soma.g_pasR
        if( idx == 9 ) g0 = soma.gbar_cat
        if( idx == 10 ) g0 = soma.gbar_k2
        if( idx == 11 ) g0 = soma.gbar_km
        if( idx == 12 ) g0 = soma.gbar_kahp
        if( idx == 13 ) g0 = soma.gbar_ar
        if( idx == 14 ) g0 = soma.gbar_skahp

        apply_one_dendcond(idx,g0)
    }

}

objref soma_vals

proc make_active_dendrite() { local val1, val2, val3, val4, sNash

     soma { 
        //if( ismembrane("naf") ) print "Soma HAS naf."  else print "Soma does NOT have naf." 
        if( !ismembrane("naf") ) {
            insert naf
	    gbar_naf = 0
        }
        sNash = fastNashift_naf
        if( !ismembrane("kdr") ) { 
	    insert kdr
	    gbar_kdr = 0
        }
        if( !ismembrane("ka") ) { 
	    insert ka
	    gbar_ka = 0
        }
        if( !ismembrane("kc") ) { 
	    insert kc
	    gbar_kc = 0
        }
        if( !ismembrane("km") ) { 
	    insert km
	    gbar_km = 0
        }
        if( !ismembrane("k2") ) { 
	    insert k2
	    gbar_k2 = 0
        }
        if( !ismembrane("kahp") ) { 
	    insert kahp
	    gbar_kahp = 0
        }
        if( !ismembrane("cal") ) { 
	    insert cal
	    gbar_cal = 0
        }
        if( !ismembrane("nap") ) { 
	    insert nap
	    gbar_nap = 0
       }
        if( !ismembrane("cad") ) { 
	    insert cad
            phi_cad = PHI_DFLT
            beta_cad = BETA_SOMA
            ceiling_cad = CEILING_CA
        }
        if( !ismembrane("cat") ) {
	    insert cat
            gbar_cat = 0
        }
        if( !ismembrane("ar") ) {
	    insert ar
            gbar_ar = 0
        }
        if( !ismembrane("skahp") ) {
	    insert skahp
            gbar_skahp = 0
        }
        soma_vals = new Vector()
        soma_vals.append(gbar_naf,gbar_kdr)
    }

    forsec dendritic {

        if( !ismembrane("naf") ) { 
	    insert naf
	    gbar_naf = 0

            tmp = sNash
            //print "soma has Na shift of ", tmp
            fastNashift_naf = tmp
            //print "just added naf to ", secname()
        }
        if( !ismembrane("kdr") ) { 
	    insert kdr
	    gbar_kdr = 0
        }
        if( !ismembrane("ka") ) { 
	    insert ka
	    gbar_ka = 0
        }
        if( !ismembrane("kc") ) { 
	    insert kc
	    gbar_kc = 0
        }
        if( !ismembrane("km") ) { 
	    insert km
	    gbar_km = 0
        }
        if( !ismembrane("k2") ) { 
	    insert k2
	    gbar_k2 = 0
        }
        if( !ismembrane("kahp") ) { 
	    insert kahp
	    gbar_kahp = 0
        }
        if( !ismembrane("cal") ) { 
	    insert cal
	    gbar_cal = 0
        }
        if( !ismembrane("nap") ) { 
	    insert nap
	    gbar_nap = 0
       }
        if( !ismembrane("cad") ) { 
	    insert cad
            phi_cad = soma.phi_cad
            beta_cad = BETA_DEND
            //ceiling_cad = soma.ceiling_cad
//printf("Added cad to %s:  %g, %g, %g\n",secname(),phi_cad,beta_cad,ceiling_cad)
        }
        if( !ismembrane("cat") ) {
if( VERBOSE ) printf("Now inserting cat.\n")
	    insert cat
            gbar_cat = 0
        }
        if( !ismembrane("ar") ) {
	    insert ar
            gbar_ar = 0
        }
        if( !ismembrane("skahp") ) {
	    insert skahp
            gbar_kahp = 0
        }

    }

    if( VERBOSE ) printf("Rendering the axon active:\n")
    forsec axonal {
        if( !ismembrane("naf") ) insert naf
        if( !ismembrane("kdr") ) insert kdr

        ifsec "AxInitSeg" {
            gbar_naf = soma_vals.x[0]
            fastNashift_naf = sNash
            gbar_kdr = soma_vals.x[1]
        } 
        ifsec "axon" {
            gbar_naf = AX_GNASCALE*soma_vals.x[0]
            fastNashift_naf = sNash
            gbar_kdr = soma_vals.x[1]
        }
        if( VERBOSE ) printf("\t%s\t%g\t%g\n",secname(),gbar_naf,gbar_kdr)
    }

//printf("From make_active_dendrite()\n")
    calc_global_slopefac(int_vec,sec_vec,slp_vec)
    apply_linear_ratios()
}



/*****************************************************************

        input    $1	1 or 0, make soma passive too?

*****************************************************************/
proc make_passive_dendrite() {

    forall {
	if( $1==0 )  ifsec "soma"  continue

        if( ismembrane("naf") ) { uninsert naf }
        if( ismembrane("kdr") ) { uninsert kdr }
        if( ismembrane("ka") ) { uninsert ka }
        if( ismembrane("kc") ) { uninsert kc }
        if( ismembrane("cal") ) { uninsert cal }
        if( ismembrane("nap") ) { uninsert nap }
        if( ismembrane("cad") ) { uninsert cad }
        if( ismembrane("cat") ) { uninsert cat }
        if( ismembrane("k2") ) { uninsert k2 }
        if( ismembrane("km") ) { uninsert km }
        if( ismembrane("kahp") ) { uninsert kahp }
        if( ismembrane("ar") ) { uninsert ar }

    }

}




/******************************************************************

    linear_passive_ratios()

    Experimentation with model "PD83" of the ball & stick model 
    suggests that using a proximal Na, NaP factor of 0.1 (relative 
    to soma value) shows a greatly reduced backpropagating AP.

    input	none

******************************************************************/
proc linear_passive_ratios() { local slp, idx, Pval, Dval

    pri_nafac = 0
    sec_nafac = 0

    pri_kfac = 0
    sec_kfac = 0

    pri_kcafac = 0
    sec_kcafac = 0

    pri_pasfac = 1
    sec_pasfac = 1

    pri_kafac = 0
    sec_kafac = 0

    pri_cafac = 0
    sec_cafac = 0

    pri_napfac = 0
    sec_napfac = 0

    pri_locafac = 0
    sec_locafac = 0

    pri_k2fac = 0
    sec_k2fac = 0 

    pri_kmfac = 0
    sec_kmfac = 0 

    pri_kahpfac = 0
    sec_kahpfac = 0 

    pri_hfac = 0
    sec_hfac = 0 


    int_vec = new Vector(14,0)
    sec_vec = new Vector(14,0)
    // passive conductance not changed.
    int_vec.x[8] = 1
    sec_vec.x[8] = 1
//printf("From linear_passive_ratios()\n")
    calc_global_slopefac(int_vec,sec_vec,slp_vec)

    apply_linear_ratios()
}



/***************************************************************

    axon_set()

    Adjust the axonal parameters.  Copied from ~ani/old_forAni/axon_set.hoc

***************************************************************/
proc axon_set() {
    forsec axon {
             gbar_naf=2.13*soma.gbar_naf
             gbar_kdr=3.2*soma.gbar_kdr
    }
    forall if (issection("AxonInitseg")){
             gbar_naf=2.13*soma.gbar_naf
             gbar_kdr=3.2*soma.gbar_kdr
    }
}


/***************************************************************

    adj_{naf, kdr, kca...} :  

    Adjust the soma value of the specified conductance,then apply 
    a linear scaling of this value throughout the dendrite.

    input	$1	somatic value to apply

***************************************************************/
proc adj_naf() { local setval

     gbar_naf = $1
    apply_one_dendcond(0,$1)
    axon_set()
    // set axonal values
    forsec "axon" {
        if( ismembrane("naf") ) {
            gbar_naf = AX_GNASCALE * $1
            if( VERBOSE ) printf("AXON:  %s gNa set to %g\n",secname(),gbar_naf)
        } else { 
            if( VERBOSE ) printf("AXON:  %s does not include gNa\n",secname())
        }
    }
    forsec "Init" {
        if( ismembrane("naf") ) {
            gbar_naf = $1
            if( VERBOSE ) printf("AXON:  %s gNa set to %g\n",secname(),gbar_naf)
        } else { 
            if( VERBOSE ) printf("AXON:  %s does not include gNa\n",secname())
        }
    }

}

proc adj_kdr() {

     gbar_kdr = $1
    apply_one_dendcond(1,$1)
      axon_set()

    /*******
    // set axonal values
    forsec "axon" {
        if( ismembrane("kdr") ) {
            gbar_kdr = $1
            if( VERBOSE ) printf("AXON:  %s gKDR set to %g\n",secname(),gbar_kdr)
        } else { 
            if( VERBOSE ) printf("AXON:  %s does not include gKDR\n",secname())
        }
    }
    ********/
    forsec "Init" {
        if( ismembrane("kdr") ) {
            gbar_kdr = $1
            if( VERBOSE ) printf("AXON:  %s gKDR set to %g\n",secname(),gbar_kdr)
        } else { 
            if( VERBOSE ) printf("AXON:  %s does not include gKDR\n",secname())
        }
    }
}

proc adj_kca() {

    gbar_kc = $1
    apply_one_dendcond(2,$1)
}

/******
*   these two procedures are included for completeness; they are 
*   also defined in adjust_procs.hoc
******/
proc adj_beta() {  local DENDSCL

    DENDSCL = 5
    soma { if( ismembrane("cad")) beta_cad = $1 }
    forall { 
        ifsec "soma" continue
	if( ismembrane("cad")) {
	  beta_cad = $1 * DENDSCL
	}
    }
}

proc adj_phi() {
	forall { if( ismembrane("cad"))  phi_cad = $1 }
}

proc adj_ka() {

    gbar_ka = $1
    apply_one_dendcond(5,$1)
}

proc adj_caL() {

    gbar_cal = $1
    apply_one_dendcond(6,$1)
}

proc adj_nap() {

    gbar_nap = $1
    apply_one_dendcond(7,$1)
}

proc adj_pas() {

    if( ismembrane("pas") ) { 
        g_pas = $1
    } else {
        if( ismembrane("pasR") ) g_pasR = $1
    }
    apply_one_dendcond(8,$1)
}

proc adj_caT() {

    gbar_cat = $1
    apply_one_dendcond(9,$1)
}

proc adj_km() {

    gbar_km = $1
    apply_one_dendcond(11,$1)
}

proc adj_k2() {

    gbar_k2 = $1
    apply_one_dendcond(10,$1)
}

proc adj_kahp() {

    gbar_kahp = $1
    apply_one_dendcond(12,$1)
}

proc adj_h() {

    gbar_ar = $1
    apply_one_dendcond(13,$1)
}

proc adj_Cm() {
    forall { cm = $1 }
    init()
}

proc adj_Ra() {
    forall { Ra = $1 }
    init()
}

proc adj_skahp() {

    gbar_skahp = $1
    apply_one_dendcond(14,$1)
}

proc add_LoCa() {
    forall {
        if( !ismembrane("cat") )  insert cat
    }
}

/**************************************************

    func find_longest_dend

    output    $s1	name of section with longest distance
              $2	segment with longest distance

**************************************************/
func find_longest_dend() { local lngdist, curdist, segID

    soma { distance() }

    strdef lng_name

    lngdist = 0
    segID = -1
    forsec dendritic {
        for(x) {
            curdist = distance(x)
            if( curdist > lngdist ) {
	        segID = x
                lng_name = secname()
                lngdist = curdist
	    }
	}
    }

    $s1 = lng_name
    $2  = segID

    //printf("Longest dendrite was %s(%d), distance from soma %g um.\n",lng_name,segID,lngdist)

    return lngdist

}

/**************************************************

    func find_shortest_dend

    output    $s1	name of section with longest distance
              $2	segment with longest distance

**************************************************/
func find_shortest_dend() { local shrtdist, curdist, segID

    soma { distance() }

    strdef shrt_name

    shrtdist = 1e6
    segID = -1
    forsec dendritic {
        for(x) {
            curdist = distance(x)
            if( curdist < shrtdist ) {
	        segID = x
                shrt_name = secname()
                shrtdist = curdist
	    }
	}
    }

    $s1 = shrt_name
    $2  = segID

    //printf("Shortest dendrite was %s(%d), distance from soma %g um.\n",shrt_name,segID,shrtdist)

    return shrtdist

}



/**************************************************

    proc shift_axonNa

    input	$1	amount to shift Na's V_half

**************************************************/
proc shift_axonNa() {

    forsec "axon" {
        fastNashift_naf = $1
    }
}


/**************************************************

    proc axonNa_hypol

    input	$1	amount to shift Na's V_half, times -1 (so we can run this in log mode)

**************************************************/
proc axonNa_hypol() {

    forsec "axon" {
        fastNashift_naf = -1*$1
    }
}




proc    set_memres() {

    forsec dendritic {
        // set membrane resistance
        RM = $1
        g_pas=1/$1
    }
    forsec axon {g_pas=1/1000}
    soma {
        // set membrane resistance
        RM = $1
        g_pas=1/$1
    }
}





/******************************************************************

    set_dend_Hratios()

    Feb 19 '13

    specify the ratio of H current at the farthest dendritic tip, 
    relative to the soma value.  Increases linearly with distance 
    from the soma.

    input	$1	ratio at tip, relative to soma 
			(e.g. $1=2 means twice the somatic value)

******************************************************************/
proc set_dend_Hratios() { local slp, idx, Pval, Dval

    int_vec.x[13] = 1
    sec_vec.x[13] = $1

    calc_global_slopefac(int_vec,sec_vec,slp_vec)
    apply_linear_ratios()
}


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