Increased computational accuracy in multi-compartmental cable models (Lindsay et al. 2005)

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Accession:129149
Compartmental models of dendrites are the most widely used tool for investigating their electrical behaviour. Traditional models assign a single potential to a compartment. This potential is associated with the membrane potential at the centre of the segment represented by the compartment. All input to that segment, independent of its location on the segment, is assumed to act at the centre of the segment with the potential of the compartment. By contrast, the compartmental model introduced in this article assigns a potential to each end of a segment, and takes into account the location of input to a segment on the model solution by partitioning the effect of this input between the axial currents at the proximal and distal boundaries of segments. For a given neuron, the new and traditional approaches to compartmental modelling use the same number of locations at which the membrane potential is to be determined, and lead to ordinary differential equations that are structurally identical. However, the solution achieved by the new approach gives an order of magnitude better accuracy and precision than that achieved by the latter in the presence of point process input.
Reference:
1 . Lindsay AE, Lindsay KA, Rosenberg JR (2005) Increased computational accuracy in multi-compartmental cable models by a novel approach for precise point process localization. J Comput Neurosci 19:21-38 [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):
Channel(s): I Na,t; I K;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON; C or C++ program;
Model Concept(s): Methods;
Implementer(s):
Search NeuronDB for information about:  I Na,t; I K;
/
LindsayEtAl2005
readme.txt
03-192.pdf
AnalyseResults.c
BitsAndPieces.c
CellData.dat
CompareSpikeTrain.c
Ed04.tex
ExactSolution.dat
GammaCode
Gen.tex
Gen1.tex
Gen2.tex
Gen3.tex
Gen4.tex
Gen5.tex
Gen6.tex
GenCom.c
GenCom1.c
GenCom2.c
GenComExactSoln.c
GenerateInput.c
GenerateInputText.c
GenRan.ran
GetNodeNumbers.c
Info100.dat
Info20.dat
Info200.dat
Info30.dat
Info300.dat
Info40.dat
Info400.dat
Info50.dat
Info500.dat
Info60.dat
Info70.dat
Info80.dat
Info90.dat
InputCurrents.dat
InputDendrite.dat
JaySpikeTrain.c
JayTest1.dat
JayTest100.dat
KenSpikeTrain.c
KenTest1.dat *
KenTest10.dat
KenTest100.dat *
KenTest10p.dat
KenTest1p.dat *
KenTest2.dat
KenTest2p.dat
KenTest3.dat
KenTest3p.dat
KenTest4.dat
KenTest4p.dat
KenTest5.dat
KenTest5p.dat
KenTest6.dat
KenTest6p.dat
KenTest7.dat
KenTest7p.dat
KenTest8.dat
KenTest8p.dat
KenTest9.dat
KenTest9p.dat
LU.c
Mean50.dat
Mean500.dat
mosinit.hoc
NC.pdf
NC.tex
NC1.tex
NC2.tex
NC3.tex
NC4.tex
NC5.tex
NC6.tex
NCFig2.eps *
NCFig3.eps *
NCFig4.eps *
NCFig5a.eps *
NCFig5b.eps *
NCFig6.eps *
NCPics.tex
NeuronDriver.hoc
NewComExactSoln.c
NewComp.pdf
NewComp.ps
NewComp.tex
NewComp.toc
NewComp1.tex
NewComp2.tex
NewComp3.tex
NewComp4.tex
NewComp5.tex
NewComp6.tex
NewCompFig1.eps
NewCompFig2.eps *
NewCompFig3.eps *
NewCompFig4.eps *
NewCompFig5a.eps *
NewCompFig5b.eps *
NewCompFig6.eps *
NewCompPics.tex
NewComSpikeTrain.c
NewRes.dat
NewRes60.dat
NewRes70.dat
NewRes80.dat
NewSynRes40.dat
NewTestCell.d3
NResults.res
OldComExactSoln.c
out.res
principles_01.tex
rand
Ratio.dat
RelErr.dat
ReviewOfSpines.pdf
SpikeTimes.dat
TestCell.d3
TestCell1.d3
TestCell2.d3
TestCell3.d3
TestCell4.d3
testcellnew2.hoc
TestCGS.c
TestGen1.c
TestSim.hoc
TestSim020.hoc
TestSim030.hoc
TestSim040.hoc
TestSim050.hoc
TestSim060.hoc
TestSim070.hoc
TestSim080.hoc
TestSim090.hoc
TestSim1.hoc
TestSim100.hoc
TestSim200.hoc
TestSim300.hoc
TestSim400.hoc
TestSim500
TestSim500.hoc
                            
#include <stdio.h>
#include <stdlib.h>
#include <math.h>
#include <string.h>


 /***************************************************************
    Function to analyse the numerical error of Generalised
    Compartmental Model. A single input is simulated and
    the exact solution determined using the Equivalent Cable
  ***************************************************************/

typedef struct SparseMatrix_t
{
        double *a;
        int *col;
        int *StartRow;
        int n;
        struct SparseMatrix_t *l;
        struct SparseMatrix_t *u;

} SparseMatrix;


typedef struct contact_t
{
        int id;                     /* Identifies contact type */

        double xp;                  /* Location of contact */
        double amp;                 /* Strength of contact */

        int xl;                     /* Left hand node */
        int xr;                     /* Right hand node */
        double frac;                /* Fraction of input to left hand node */

        struct contact_t *next;     /* Address of next contact */
} contact;


typedef struct branch_t
{
/*  Connectivity of branch */
        struct branch_t *parent;    /* Address of parent branch */
        struct branch_t *child;     /* Address of child branch */
        struct branch_t *peer;      /* Addresss of peer branch */

/*  Physical properties of branch */
        int nd;                     /* Number of nodes on branch specification */
        double xl;                  /* X-coordinate of lefthand endpoint */
        double yl;                  /* Y-coordinate of lefthand endpoint */
        double zl;                  /* Z-coordinate of lefthand endpoint */
        double xr;                  /* X-coordinate of righthand endpoint */
        double yr;                  /* Y-coordinate of righthand endpoint */
        double zr;                  /* Z-coordinate of righthand endpoint */
        double diam;                /* Branch diameter (microns) */
        double plen;                /* Branch length (microns) */
        double elen;                /* Branch length (eu) */

        double *d;                  /* Diameter of dendrite (micron) */
        double *x;                  /* Location of nodes on dendrite (micron) */

/*  Node information for spatial representation */
        int nodes;                  /* Total number nodes spanning branch */
        int junct;                  /* Junction node of the branch */
        int first;                  /* Internal node connected to junction */

/*  Contact information */
        contact *conlist;               /* Branch contact */
} branch;


typedef struct dendrite_t
{
        branch *root;               /* Pointer to root branch of dendrite */
        double plen;                /*  length of dendrite */
} dendrite;


typedef struct neuron_t
{
        int ndend;                  /* Number of dendrites */
        dendrite *dendlist;         /* Pointer to an array of dendrites */
} neuron;


/* Function type declarations */
int     Count_Branches( branch *, branch *),
        Count_Contacts( branch *, branch *);

double  branch_length( branch *, branch *),
        ran(unsigned int *, unsigned int *, unsigned int *);

void    Build_Test_Dendrite( branch **, branch *),
        Remove_Branch( branch **, branch *),
        Destroy_Test_Neuron( neuron *),
        Destroy_Test_Dendrite( branch *),
        Find_Contacts( branch *, double *, double *, int *),

        Assign_Branch_Nodes( branch *, double *),
        Enumerate_Nodes( branch *, int *),
        Generate_Dendrite(branch *, int *),
        Input_Current( branch *),
        Assign_Current( branch *, double *, double ),

        Matrix_Vector_Multiply( SparseMatrix *, double *, double *),
        Matrix_Malloc( SparseMatrix *, int, int),
        Matrix_Free( SparseMatrix *),
        LU_Factor(SparseMatrix *, int *),
        LU_Solve( SparseMatrix *, double *, double *);

/* Global definitions */
#define             CS    1.0
#define             GS    0.091
#define             GA    14.286
#define             CM    1.0
#define             GM    0.091
#define         OUTPUT    "contactinfo.dat"
#define           TEND    10.0
#define           NSIM    1      /* Simulations to be done */
#define             NT    1000
#define             DT    1.0
#define          NODES    100
#define          NSEED    7    /* Seed for random number generator */
#define          FSEED    "GenRan.ran"  /* History of random number generator */

/* Parameters for exact solution */
#define           NCON    1  /* Number of contacts */
#define            AMP    0.0e-3
#define            SIN    1.0e-3
#define              T    10.0
#define              M    1000

/* Parameters for TestCell1.d3 (unbranched dendrite) */
// #define             RS    0.002
// #define             RD    0.001
// #define              L    0.100
// #define              X    0.055

/* Parameters for TestCell3.d3 (Y-junction) */
// #define             RS    0.002
// #define             RD    0.000354487542
// #define              L    0.0500427736
// #define              X    0.039163520

/* Parameters for TestCell2.d3 (Y-junction) */
// #define             RS    0.002
// #define             RD    0.000354487542
// #define              L    0.0667236981
// #define              X    0.010

/* Parameters for TestCell4.d3 (large branched dendrite) */
 #define             RS    0.002
 #define             RD    0.000648741708
 #define              L    0.2256605
 #define              X    0.0135280571

/* Global Variables */
SparseMatrix lhs, rhs;
unsigned int ix, iy, iz;

int main( int argc, char **argv )
{
    extern unsigned int ix, iy, iz;
    int k, j, id, start, begin, nodes, n, nc, i, in,
        ncon, FirstNode, NumberOfInput;
    int counter, nb, nsim, connected;
    double *v, *x, max, *eta, *eval, *cval, AreaOfSoma, gama,
           *chi, xold, xnew, frac, arg, sum, tmp, vs, pi, dt,
           tnow, tout, len, h, CableDiameter, ElectrotonicLength,
           *amp, *loc, input, CableLength, dx, CellLength, LocusContact;
    void srand( unsigned int);
    neuron *cell;
    contact *newcon, *oldcon, *con;
    extern SparseMatrix lhs, rhs;
    branch *bnow, *bold, *bnew, *FirstBranch, *CellFirstBranch;
    char word[20];
    FILE *fp;

/*  Initialise simulation counter */
    nsim = 1;
    start = 1;

    if ( (fp=fopen(FSEED,"r"))!=NULL ) {
        while ( fscanf(fp,"%lu %lu %lu", &ix, &iy, &iz )!=EOF ) nsim++;
        fclose(fp);
    } else {
        srand( ((unsigned int) NSEED) );
        ix = rand( );
        iy = rand( );
        iz = rand( );
    }

/*  Load Test Neuron */
    if ( argc != 2 ) {
        printf("\n Invoke program with load <input>\n");
        return 1;
    } else {
        printf("\nOpening file %s\n",argv[1]);
        if ( (fp=fopen(argv[1],"r")) == NULL ) {
            printf("\n Test Neuron file does not found");
            return 1;
        }
        pi = 4.0*atan(1.0);

/*  Get branch data */
        bold = NULL;
        while  ( fscanf(fp,"%s",word) != EOF ) {
            if ( strcmp(word,"Branch") == 0 || strcmp(word,"branch") == 0 ) {
                fscanf(fp, "%d", &nodes);
                printf("Found a branch defined by %d nodes\n", nodes);
                bnew = (branch *) malloc( sizeof(branch) );
                bnew->peer = NULL;
                bnew->child = NULL;
                bnew->d = NULL;
                bnew->x = NULL;
                bnew->conlist = NULL;
                if ( bold != NULL) {
                    bold->child = bnew;
                } else {
                    CellFirstBranch = bnew;
                }
                bnew->parent = bold;
                fscanf(fp,"%lf %lf %lf", &(bnew->xl), &(bnew->yl), &(bnew->zl) );
                fscanf(fp,"%lf %lf %lf", &(bnew->xr), &(bnew->yr), &(bnew->zr) );
                fscanf(fp,"%lf %lf", &(bnew->plen), &(bnew->diam) );
                bnew->elen = (bnew->plen)/sqrt(bnew->diam);
                bold = bnew;
            } else if ( strcmp(word,"Marker") == 0 || strcmp(word,"marker") == 0 ) {
                printf("Found and initialised a branch contact\n");
                newcon = (contact *) malloc( sizeof(contact) );
                newcon->next = NULL;
                fscanf(fp,"%lf %lf", &newcon->xp, &newcon->amp );
                if ( bnew->conlist == NULL ) {
                    bnew->conlist = newcon;
                } else {
                    con = bnew->conlist;
                    while ( con->next ) con = con->next;
                    con->next = newcon;
                }
            } else {
                printf("Unrecognised dendritic feature\n");
            }
        }
        fclose(fp);
    }

/*  Compute total length of dendrite */
    CellLength = 0.0;
    bnew = CellFirstBranch;
    while ( bnew ) {
       CellLength += bnew->plen;
       bnew = bnew->child;
    }

/*  Start simulation procedure */
    while ( nsim <= NSIM ) {

/*  Step 1. - Generate a copy of the branch list */
        bnow = CellFirstBranch;
        bold = NULL;
        while ( bnow != NULL ) {
            bnew = (branch *) malloc( sizeof(branch) );
            bnew->xl = bnow->xl;
            bnew->yl = bnow->yl;
            bnew->zl = bnow->zl;
            bnew->xr = bnow->xr;
            bnew->yr = bnow->yr;
            bnew->zr = bnow->zr;
            bnew->diam = bnow->diam;
            bnew->plen = bnow->plen;
            bnew->elen = bnow->elen;
            bnew->peer = NULL;
            bnew->child = NULL;
            bnew->d = NULL;
            bnew->x = NULL;
            if ( bold != NULL ) {
                bold->child = bnew;
            } else {
                FirstBranch = bnew;
            }
            bnew->parent = bold;
            bold = bnew;

            if ( bnow->conlist ) {
                oldcon = NULL;
                con = bnow->conlist;
                while ( con ) {
                    newcon = (contact *) malloc( sizeof(contact) );
                    newcon->next = NULL;
                    newcon->frac = NULL;
                    newcon->amp = con->amp;
                    newcon->id = con->id;
                    newcon->xp = con->xp;
                    newcon->xl = NULL;
                    newcon->xr = NULL;
                    if ( oldcon != NULL ) {
                        oldcon->next = newcon;
                    } else {
                        bnew->conlist = newcon;
                    }
                    oldcon = newcon;
                    con = con->next;
                }
            } else {
                bnew->conlist = NULL;
            }

            bnow = bnow->child;
        }

/*  STEP 1. - Randomly place NCON inputs on branches */
        for ( k=0 ; k<NCON ; k++ ) {
            LocusContact = CellLength*ran( &ix, &iy, &iz);
            bnew = FirstBranch;
            len = bnew->plen;
            while ( LocusContact > len ) {
                bnew = bnew->child;
                len += bnew->plen;
            }
            newcon = (contact *) malloc( sizeof(contact) );
            newcon->next = NULL;
            newcon->frac = NULL;
            newcon->amp = AMP;
            newcon->xl = NULL;
            newcon->xr = NULL;
            newcon->xp = LocusContact-(len-bnew->plen);
            if ( bnew->conlist ) {
                oldcon = bnew->conlist;
                while ( oldcon->next ) oldcon = oldcon->next;
                oldcon->next = newcon;
            } else {
                bnew->conlist = newcon;
            }
        }

/*  STEP 2. - Count root branches */
        bold = FirstBranch;
        n = 0;
        while ( bold ) {
            bnew = FirstBranch;
            do {
                tmp = pow(bold->xl-bnew->xr,2)+
                      pow(bold->yl-bnew->yr,2)+
                      pow(bold->zl-bnew->zr,2);
                connected = ( tmp < 0.01 );
                bnew = bnew->child;
            } while ( bnew && !connected );
            if ( !connected ) n++;
            bold = bold->child;
        }

/*  STEP 3. - Identify somal dendrites but extract nothing */
        printf("\nTree contains %d individual dendrite(s) ...\n", n);
        cell = (neuron *) malloc( sizeof(neuron) );
        cell->ndend = n;
        cell->dendlist = (dendrite *) malloc( n*sizeof(dendrite) );
        bold = FirstBranch;
        n = 0;
        while ( n < cell->ndend ) {
            bnew = FirstBranch;
            do {
                tmp = pow(bold->xl-bnew->xr,2)+
                      pow(bold->yl-bnew->yr,2)+
                      pow(bold->zl-bnew->zr,2);
                connected = ( tmp < 0.01 );
                bnew = bnew->child;
            } while ( bnew );
            if ( !connected ) cell->dendlist[n++].root = bold;
            bold = bold->child;
        }

/*  STEP 4. - Extract root of each dendrite from dendrite list */
        for ( k=0 ; k<cell->ndend ; k++ ) {
            bold = cell->dendlist[k].root;
            Remove_Branch( &FirstBranch, bold);
        }

/*  STEP 5. - Build each test dendrite from its root branch */
        for ( k=0 ; k<cell->ndend ; k++ ) {
            Build_Test_Dendrite( &FirstBranch, cell->dendlist[k].root );
        }
        if ( FirstBranch != NULL ) printf("\nWarning: Unconnected branch segments still exist\n");

/*  STEP 6A. - Identify scaled soma-to-tip electrotonic length */
        ElectrotonicLength = 0.0;
        bnow = cell->dendlist[0].root;
        while ( bnow != NULL ) {
            ElectrotonicLength += bnow->elen;
            bnow = bnow->child;
        }

/*  STEP 6B. - Identify diameter of equivalent cable */
        CableDiameter = 0.0;
        for ( k=0 ; k<cell->ndend ; k++ ) {
            CableDiameter += pow(cell->dendlist[k].root->diam,1.5);
        }
        CableDiameter = pow(CableDiameter,2.0/3.0);

/*  STEP 6C. - Compute length of equivalent cable */
        CableLength = ElectrotonicLength*sqrt(CableDiameter);

/*  STEP 7A. - Count number on inputs on Cell */
        NumberOfInput = 0;
        for ( k=0 ; k<cell->ndend ; k++ ) {
            bnow = cell->dendlist[k].root;
            NumberOfInput += Count_Contacts( cell->dendlist[k].root, bnow);
        }
        amp = (double *) malloc( NumberOfInput*sizeof(double) );
        loc = (double *) malloc( NumberOfInput*sizeof(double) );

/*  STEP 7B. - Identify position of contacts on Equivalent Cable */
        for ( ncon=k=0 ; k<cell->ndend ; k++ ) {
            bnow = cell->dendlist[k].root;
            Find_Contacts( bnow, loc, amp, &ncon);
        }
        tmp = sqrt(CableDiameter);
        for ( k=0 ; k<ncon ; k++ ) loc[k] *= tmp;
        if ( ncon == 0 ) {
            printf("\n No contact found - Fatal error!");
            return 1;
        }

/*  STEP 8. - Construct exact solution */
        if ( start ) {
            frac = loc[0]/CableLength;
            AreaOfSoma = 4.0*pi*RS*RS;
            gama = AreaOfSoma/(pi*CableDiameter*CableLength);
            eta = (double *) malloc( (M+1)*sizeof(double) );
            chi = (double *) malloc( (M+1)*sizeof(double) );
            eval = (double *) malloc( (M+1)*sizeof(double) );
            cval = (double *) malloc( (M+1)*sizeof(double) );
            eta[0] = GM/CM;
            chi[0] = (AMP+SIN)/(pi*CM*CableDiameter*CableLength*(1.0+gama));
            chi[0] /= eta[0];
            eval[0] = 0.0;
            cval[0] = 1.0;
            for ( k=1 ; k<=M ; k++ ) {
                xnew = arg = pi*((double) k );
                do {
                    xold = xnew;
                    xnew = arg-atan(gama*xold);
                } while ( fabs(xold-xnew) > 5.e-7 );
                eval[k] = xnew;
                cval[k] = cos(xnew);
            }
        }
        for ( k=1 ; k<=M ; k++ ) {
            eta[k] = (GM+0.25*CableDiameter*GA*pow(eval[k]/CableLength,2) )/CM;
            chi[k] = 2.0*cval[k]*(AMP*cos(eval[k]*(1.0-frac))+SIN*cval[k])/
                         (pi*CM*CableDiameter*CableLength*(1.0+gama*cval[k]*cval[k]));
            chi[k] /= eta[k];
        }

/*  STEP 9. - Count dendritic segments */
        for ( nb=k=0 ; k<cell->ndend ; k++ ) {
            bnow = cell->dendlist[k].root;
            nb += Count_Branches( bnow, bnow);
        }
        h = CellLength/((double) NODES-nb);
        for ( k=0 ; k<cell->ndend ; k++ ) Assign_Branch_Nodes( cell->dendlist[k].root, &h);

/*  STEP 10. - Enumerate Nodes */
        FirstNode = 0;
        for ( k=0 ; k<cell->ndend ; k++ ) Enumerate_Nodes( cell->dendlist[k].root, &FirstNode );
        for ( k=0 ; k<cell->ndend ; k++ ) cell->dendlist[k].root->junct = FirstNode;
        printf("Number of nodes is %d\n", FirstNode+1);
        getchar( );

/*  STEP 11. - Construct Sparse Matrices */
        nodes = FirstNode+1;
        if ( start ) {
            Matrix_Malloc( &lhs, nodes, 3*nodes-2 );
            Matrix_Malloc( &rhs, nodes, 3*nodes-2 );
        }
        lhs.n = rhs.n = nodes;
        lhs.a[3*nodes-3] = rhs.a[3*nodes-3] = 0.0;
        lhs.StartRow[0] = rhs.StartRow[0] = 0;

        for ( counter=k=0 ; k<cell->ndend ; k++ ) {
            bnow = cell->dendlist[k].root;
            Generate_Dendrite( bnow, &counter);
        }
        printf("Generated numerical representation of dendrite\n");
        getchar( );

        for ( k=0 ; k<cell->ndend ; k++ ) {
            bnow = cell->dendlist[k].root;
            lhs.a[counter] = 0.5*bnow->d[1]*bnow->x[1];
            rhs.a[counter] = -(bnow->d[0])*(bnow->d[1])/bnow->x[1];
            lhs.col[counter] = rhs.col[counter] = bnow->first;
            lhs.a[3*nodes-3] += 1.5*(bnow->d[0])*bnow->x[1];
            rhs.a[3*nodes-3] += (bnow->d[0])*(bnow->d[1])/bnow->x[1];
            counter++;
        }
        lhs.col[3*nodes-3] = rhs.col[3*nodes-3] = nodes-1;
        lhs.StartRow[nodes] = rhs.StartRow[nodes] = 3*nodes-2;

        for( k=0 ; k<cell->ndend ; k++ ) Input_Current(cell->dendlist[k].root);

        fp = fopen("out.res", "w");
        fclose(fp);
        printf("Constructed sparse matricesn");
        getchar( );

        dt = 1.0/((double) NT);
        for ( k=0 ; k<3*nodes-2 ; k++ ) {
            rhs.a[k] *= GA;
            rhs.a[k] += GM*lhs.a[k];
            lhs.a[k] *= CM;
            rhs.a[k] *= 0.5*dt;
            lhs.a[k] += rhs.a[k];
            rhs.a[k] = lhs.a[k]-2.0*rhs.a[k];
        }

/*  Add capacitive term of soma */
        lhs.a[3*nodes-3] += (4.0*AreaOfSoma/pi)*(CS+0.5*GS*dt);
        rhs.a[3*nodes-3] += (4.0*AreaOfSoma/pi)*(CS-0.5*GS*dt);

        if ( start ) {
            v = (double *) malloc( (nodes)*sizeof(double) );
            x = (double *) malloc( (nodes)*sizeof(double) );
        }
        for ( k=0 ; k<nodes ; k++ ) v[k] = x[k] = 0.0;
        begin = 1;
        LU_Factor(&lhs, &begin);

/*  Initialise temporal integration */
        tnow = 0.0;
        tout = DT;
        while ( tnow < TEND ) {
            tnow += dt;
            Matrix_Vector_Multiply(&rhs,v,x);
            x[nodes-1] -= 4.0*dt*SIN/pi;
            tmp = 4.0*dt/pi;
            for ( k=0 ; k<nodes ; k++ ) v[k] = x[k];
            if ( tnow < T ) {
                for ( k=0 ; k<cell->ndend ; k++ ) Assign_Current(cell->dendlist[k].root, x, tmp);
            }
            LU_Solve( &lhs, v, x );

            if ( tnow > tout && tnow <= T ) {
                printf("\rReached time %5.1lf ms\t", tout);
                for ( vs=0.0,k=M ; k>=0 ; k-- ) {
                    arg = tnow*eta[k];
                    if ( arg > 20.0 ) {
                        tmp = 1.0;
                    } else {
                        tmp = (1.0-exp(-arg));
                    }
                    vs -= tmp*chi[k];
                }
                printf("\nNumerical Voltage %12.6lf mV\n",v[nodes-1]);
                printf("Exact Voltage %12.6lf mV\n", vs);
                tout += DT;
                fp = fopen("out.res", "a");
                fprintf(fp,"Error %12.6lf% \n",fabs((v[nodes-1]-vs)/(0.01*vs)));
                fclose(fp);
            }
            if ( tnow > tout && tnow > T ) {
                printf("\rReached time %5.1lf ms\t", tout);
                for ( vs=0.0,k=M ; k>=0 ; k-- ) {
                    arg = (tnow-T)*eta[k];
                    if ( arg < 20.0 ) {
                        tmp = exp(-arg);
                        arg = tnow*eta[k];
                        if ( arg < 20.0 ) tmp -= exp(-arg);
                        vs -= tmp*chi[k];
                    }
                }
                printf("\nNumerical Voltage %12.6lf mV\n",v[nodes-1]);
                printf("Exact Voltage %12.6lf mV\n",vs);
                tout += DT;
                fp = fopen("out.res", "a");
                fprintf(fp,"Error %12.6lf% \n",fabs((v[nodes-1]-vs)/(0.01*vs)));
                fclose(fp);
            }
        }

        free(amp);
        free(loc);
        Destroy_Test_Neuron( cell );

/*  Update seed file */
        if ( nsim == 1 ) {
            fp = fopen(FSEED,"w");
        } else {
            fp = fopen(FSEED,"a");
        }
        fprintf(fp,"%u \t %u \t %u\n", ix, iy, iz);
        fclose(fp);
        if ( start ) start = 0;
        nsim++;
    }
    return 0;
}


 /******************************************************
     Function to build a test dendrite from its root
  ******************************************************/
void Build_Test_Dendrite( branch **head, branch *root)
{
    double tmp;
    branch *bnow, *bnext, *btmp;

    bnow = *head;
    while ( bnow != NULL ) {

/*  Store bnow's child in case it's corrupted */
        bnext = bnow->child;

/*  Decide if proximal end of bnow is connected to distal end of root */
        tmp = pow(bnow->xl-root->xr,2)+
              pow(bnow->yl-root->yr,2)+
              pow(bnow->zl-root->zr,2);
        if ( tmp <= 0.01 ) {

/*  Remove bnow from the branch list */
            Remove_Branch( head, bnow);

/*  Connect bnow to the root as the child or a peer of the child.
    Initialise childs' children and peers to NULL as default */
            bnow->child = NULL;
            bnow->peer = NULL;
            bnow->parent = root;

/*  Inform root about its child if it's the first child, or add
    new child to first child's peer list */
            if ( root->child != NULL ) {
                btmp = root->child;
                while ( btmp->peer != NULL ) btmp = btmp->peer;
                btmp->peer = bnow;
            } else {
                root->child = bnow;
            }
        }

/*  Initialise bnow to next branch in list */
        bnow = bnext;
    }

/* Iterate through remaining tree */
    if ( root->child ) Build_Test_Dendrite( head, root->child);
    if ( root->peer ) Build_Test_Dendrite( head, root->peer);
    return;
}


 /*********************************************************
        Function to remove a branch from a branch list
  *********************************************************/
void Remove_Branch(branch **head, branch *b)
{
    if ( *head == NULL || b == NULL ) return;
    if ( *head == b ) {
        *head = b->child;
        if ( *head != NULL )  (*head)->parent = NULL;
    } else {
        b->parent->child = b->child;
        if ( b->child != NULL ) b->child->parent = b->parent;
    }
    b->parent = NULL;
    b->child = NULL;
    return;
}


 /************************************************
         Function to destroy a TEST NEURON
  ************************************************/
void Destroy_Test_Neuron(neuron *cell)
{
    int k;

    for ( k=0 ; k<cell->ndend ; k++ ) {
        Destroy_Test_Dendrite( cell->dendlist[k].root );
    }
    free(cell);
    return;
}


 /***************************************************
              Function to destroy TEST DENDRITE
  ***************************************************/
void Destroy_Test_Dendrite( branch *b )
{
    int i;
    contact *prevcon, *nextcon;

    if ( b->child ) Destroy_Test_Dendrite(b->child);
    if ( b->peer ) Destroy_Test_Dendrite(b->peer);
    free( b->d );
    free( b->x );
    if ( b->conlist ) {
        prevcon = b->conlist;
        do {
            nextcon = prevcon->next;
            free(prevcon);
            prevcon = nextcon;
        } while ( prevcon );
    }
    free (b);
    return;
}


 /*********************************************
      Function to count contacts on branches
  *********************************************/
int Count_Contacts( branch *bstart, branch *bnow)
{
    static int n;
    contact *con;

    if ( bstart == bnow ) n = 0;
    if ( bnow != NULL ) {
        if ( bnow->child ) Count_Contacts(bstart, bnow->child);
        if ( bnow->peer ) Count_Contacts(bstart, bnow->peer);
        con = bnow->conlist;
        while ( con ) {
            n++;
            con = con->next;
        }
    }
    return n;
}


 /**********************************************
      Function to count number of branches
  **********************************************/
int Count_Branches( branch *bstart, branch *bnow)
{
    static int n;

    if ( bstart == bnow ) n = 0;
    if ( bnow != NULL ) {
        if ( bnow->child ) Count_Branches(bstart, bnow->child);
        if ( bnow->peer ) Count_Branches(bstart, bnow->peer);
        n++;
    }
    return n;
}


 /***************************************************
       Function to find contacts on a dendrite
  ***************************************************/
void Find_Contacts( branch *b, double *loc, double *amp, int *ncon)
{
    contact *con;
    branch *btmp;

    if ( b->child ) Find_Contacts( b->child, loc, amp, ncon);
    if ( b->peer ) Find_Contacts( b->peer, loc, amp, ncon);
    con = b->conlist;
    if ( con ) {
        amp[(*ncon)] = con->amp;
        loc[(*ncon)] = (con->xp)/sqrt(b->diam);
        btmp = b->parent;
        while ( btmp ) {
            loc[(*ncon)] += btmp->elen;
            btmp = btmp->parent;
        }
        (*ncon)++;
    }
    return;
}


 /*******************************************************
       Function to enumerate the nodes on a dendrite
  *******************************************************/
void Enumerate_Nodes(branch *bnow, int *FirstNode )
{
    branch *btmp;

    if ( bnow->child ) Enumerate_Nodes( bnow->child, FirstNode );
    if ( bnow->peer ) Enumerate_Nodes( bnow->peer, FirstNode );

    if ( bnow->child ) {
        btmp = bnow->child;
        while ( btmp ) {
            btmp->junct = *FirstNode;
            btmp = btmp->peer;
        }
    }
    *FirstNode += (bnow->nd)-1;
    bnow->first = *FirstNode-1;
    return;
}


 /***************************************************
        Function to constuct sparse matrices
  ***************************************************/
void Generate_Dendrite( branch *bnow, int *counter)
{
    int i, k, n;
    extern SparseMatrix lhs, rhs;
    branch *btmp;
    double SumL, SumR;

/* Step 1 - Recurse to the end of the dendrite */
    if ( bnow->child ) Generate_Dendrite( bnow->child, counter);
    if ( bnow->peer ) Generate_Dendrite( bnow->peer, counter);

/* Step 2 - Build matrix entries for distal node of branch */
    n = (bnow->nd)-1;
    k = (bnow->first)-(bnow->nd)+2;
    if ( bnow->child ) {
        btmp = bnow->child;
        SumR = SumL = 0.0;
        while ( btmp ) {
            lhs.a[*counter] = 0.5*btmp->d[1]*btmp->x[1];
            rhs.a[*counter] = -(btmp->d[0]*btmp->d[1])/btmp->x[1];
            lhs.col[*counter] = rhs.col[*counter] = btmp->first;
            SumL += 1.5*btmp->d[0]*btmp->x[1];
            SumR += (btmp->d[0]*btmp->d[1])/btmp->x[1];
            (*counter)++;
            btmp = btmp->peer;
        }
        lhs.a[*counter] = SumL+1.5*bnow->d[n]*(bnow->x[n]-bnow->x[n-1]);
        rhs.a[*counter] = SumR+(bnow->d[n-1]*bnow->d[n])/(bnow->x[n]-bnow->x[n-1]);
        lhs.col[*counter] = rhs.col[*counter] = k;
        (*counter)++;
        lhs.a[*counter] = 0.5*(bnow->d[n-1])*(bnow->x[n]-bnow->x[n-1]);
        rhs.a[*counter] = -(bnow->d[n-1]*bnow->d[n])/(bnow->x[n]-bnow->x[n-1]);
        if ( k == bnow->first ) {
            lhs.col[*counter] = rhs.col[*counter] = bnow->junct;
        } else {
            lhs.col[*counter] = rhs.col[*counter] = k+1;
        }
        (*counter)++;
        lhs.StartRow[k+1] = rhs.StartRow[k+1] = *counter;
    } else {
        lhs.a[*counter] = 1.5*(bnow->d[n])*(bnow->x[n]-bnow->x[n-1]);
        rhs.a[*counter] = (bnow->d[n-1]*bnow->d[n])/(bnow->x[n]-bnow->x[n-1]);
        lhs.col[*counter] = rhs.col[*counter] = k;
        (*counter)++;
        lhs.a[*counter] = 0.5*(bnow->d[n-1])*(bnow->x[n]-bnow->x[n-1]);
        rhs.a[*counter] = -(bnow->d[n-1]*bnow->d[n])/(bnow->x[n]-bnow->x[n-1]);
        if ( k == bnow->first ) {
            lhs.col[*counter] = rhs.col[*counter] = bnow->junct;
        } else {
            lhs.col[*counter] = rhs.col[*counter] = k+1;
        }
        (*counter)++;
        lhs.StartRow[k+1] = rhs.StartRow[k+1] = *counter;
    }

/* Step 3 - Build matrix entries for internal node of branch */
    for ( i=(bnow->nd)-2 ; i>0 ; i-- ) {
        k = bnow->first+1-i;
        lhs.a[*counter] = 0.5*(bnow->d[i+1])*(bnow->x[i+1]-bnow->x[i]);
        rhs.a[*counter] = -(bnow->d[i]*bnow->d[i+1])/(bnow->x[i+1]-bnow->x[i]);
        lhs.col[*counter] = rhs.col[*counter] = k-1;
        (*counter)++;
        lhs.a[*counter] = 1.5*(bnow->d[i])*(bnow->x[i+1]-bnow->x[i-1]);
        rhs.a[*counter] = (bnow->d[i-1]*bnow->d[i])/(bnow->x[i]-bnow->x[i-1])
                          +(bnow->d[i]*bnow->d[i+1])/(bnow->x[i+1]-bnow->x[i]);
        lhs.col[*counter] = rhs.col[*counter] = k;
        (*counter)++;
        lhs.a[*counter] = 0.5*(bnow->d[i-1])*(bnow->x[i]-bnow->x[i-1]);
        rhs.a[*counter] = -(bnow->d[i-1]*bnow->d[i])/(bnow->x[i]-bnow->x[i-1]);
        lhs.col[*counter] = rhs.col[*counter] = k+1;
        if ( k == bnow->first ) {
            lhs.col[*counter] = rhs.col[*counter] = bnow->junct;
        } else {
            lhs.col[*counter] = rhs.col[*counter] = k+1;
        }
        (*counter)++;
        lhs.StartRow[k+1] = rhs.StartRow[k+1] = *counter;
    }
    return;
}


 /***********************************************
       Function to input current to dendrite
  ***********************************************/
void Input_Current( branch *bnow )
{
    int k;
    double tmp;
    contact *con;

    if ( bnow->child ) Input_Current( bnow->child );
    if ( bnow->peer ) Input_Current( bnow->peer );

    con = bnow->conlist;
    while ( con ) {
        if ( con->xp <= bnow->x[1] ) {
            con->xl = bnow->junct;
            con->xr = bnow->first;
            con->frac = 1.0-(con->xp)/(bnow->x[1]);
        } else {
            k = 1;
            while ( con->xp > bnow->x[k] ) k++;
            con->xl = bnow->first-k+2;
            con->xr = bnow->first-k+1;
            con->frac = (bnow->x[k]-con->xp)/(bnow->x[k]-bnow->x[k-1]);
        }
        con = con->next;
    }
    return;
}


 /****************************************
        Function to assign current
  ****************************************/
void Assign_Current(branch *bnow, double *x, double fac )
{
    contact *con;

    if ( bnow->child ) Assign_Current(bnow->child, x, fac );
    if ( bnow->peer ) Assign_Current(bnow->peer, x, fac );

    con = bnow->conlist;
    while ( con ) {
        x[con->xl] -= fac*(con->frac)*(con->amp);
        x[con->xr] -= fac*(1.0-(con->frac))*(con->amp);
        con = con->next;
    }
    return;
}


 /**********************************************************
     Multiplies sparse matrix a[ ][ ] with vector v[ ]
  **********************************************************/
void Matrix_Vector_Multiply( SparseMatrix *a, double *v , double *b)
{
    int i, j, k, n;

    n = a->n;
    for ( j=0 ; j<n ; j++) {
        k = a->StartRow[j+1];
        for( b[j]=0.0,i=(a->StartRow[j]) ; i<k ; i++ ) {
            b[j] += (a->a[i])*v[a->col[i]];
        }
    }
    return;
}


 /***********************************************
        Allocate memory to a sparse matrix
  ***********************************************/
void Matrix_Malloc( SparseMatrix *a, int n, int w)
{
    a->a = (double *) malloc( w*sizeof(double) );
    a->col = (int *) malloc( w*sizeof(int) );
    a->StartRow = (int *) malloc( (n+1)*sizeof(int) );
    a->n = n;
    a->l = malloc(sizeof(SparseMatrix));
    a->u = malloc(sizeof(SparseMatrix));
    a->l->a = (double *) malloc( (2*n-1)*sizeof(double) );
    a->l->col = (int *) malloc( (2*n-1)*sizeof(int) );
    a->l->StartRow = (int *) malloc( (n+1)*sizeof(int) );
    a->l->n = n;
    a->u->a = (double *) malloc( (2*n-1)*sizeof(double) );
    a->u->col = (int *) malloc( (2*n-1)*sizeof(int) );
    a->u->StartRow = (int *) malloc( (n+1)*sizeof(int) );
    a->u->n = n;
    return;
}


 /**********************************************
     De-allocates memory of a sparse matrix
  **********************************************/
void Matrix_Free( SparseMatrix *a)
{
    free(a->a);
    free(a->col);
    free(a->StartRow);
    free(a);
}


 /***********************************************
      Function To Factorise A Sparse Matrix
  ***********************************************/
void LU_Factor(SparseMatrix *m, int *start)
{
    double tmp, sum;
    int i, j, k, r, n, cl, cu, col, row;

/*  Step 1. - Identify matrix dimension */
    n = m->n;

/*  Step 2. - Fill column vectors for triangular matrices */
    if ( *start ) {
        cl = cu = 0;
        for ( i=k=0 ; i<n ; i++ ) {
            m->l->StartRow[i] = cl;
            m->u->StartRow[i] = cu;
            while ( m->col[k] < i ) m->l->col[cl++] = m->col[k++];
            m->l->col[cl++] = m->col[k];
            m->u->col[cu++] = m->col[k++];
            while ( k < m->StartRow[i+1] ) m->u->col[cu++] = m->col[k++];
        }
        m->l->StartRow[n] = cl;
        m->u->StartRow[n] = cu;
        *start = 0;
    }

/*  Step 3. - Fill remaining entries of L and U row by row */
    cl = cu = 0;
    for ( i=0 ; i<n ; i++ ) {
        for ( k=m->StartRow[i] ; k < m->StartRow[i+1] ; k++ ) {
            if ( m->col[k] < i ) {
                sum = m->a[k];
                for ( j=m->l->StartRow[i] ; j<cl ; j++ ) {
                    col = m->l->col[j];
                    row = m->u->StartRow[col];
                    while ( m->u->col[row] < m->col[k] && row < m->u->StartRow[col+1] ) row++;
                    if ( m->u->col[row] == m->col[k] ) sum -= (m->l->a[j])*(m->u->a[row]);
                }
                row = m->u->StartRow[m->l->col[cl]];
                while ( m->u->col[row] < m->col[k] ) row++;
                m->l->a[cl++] = sum/(m->u->a[row]);
            } else if ( m->col[k] == i ) {
                m->l->a[cl++] = 1.0;
                sum = m->a[k];
                for ( j=m->l->StartRow[i] ; j<m->l->StartRow[i+1]-1; j++ ) {
                    col = m->l->col[j];
                    row = m->u->StartRow[col];
                    while ( m->u->col[row] < i && row < m->u->StartRow[col+1] ) row++;
                    if ( m->u->col[row] == i ) sum -= (m->l->a[j])*(m->u->a[row]);
                }
                m->u->a[cu++] = sum;
            } else {
                sum = m->a[k];
                for ( j=m->l->StartRow[i] ; j<m->l->StartRow[i+1]-1; j++ ) {
                    col = m->l->col[j];
                    row = m->u->StartRow[col];
                    while ( m->u->col[row] < m->col[k] && row < m->u->StartRow[col+1] ) row++;
                    if ( m->u->col[row] == m->col[k] ) sum -= (m->l->a[j])*(m->u->a[row]);
                }
                m->u->a[cu++] = sum;
            }
        }
    }
    return;
}


 /**************************************************
          Function to Solve the matrix problem
  **************************************************/
void LU_Solve(SparseMatrix *m, double *x, double *b )
{
    int i,j;
    double *z;

    z = (double *) malloc( (m->n)*sizeof(double) );

    for ( i=0 ; i<m->n ; i++ ) {
        z[i] = b[i];
        for (j=m->l->StartRow[i];j<m->l->StartRow[i+1]-1;j++)
        { z[i] -= (m->l->a[j])*(z[(m->l->col[j])]); }
        z[i] /= m->l->a[m->l->StartRow[i+1]-1];
    }

    for ( i = (m->n) - 1 ; i>=0 ; i-- ) {
        x[i] = z[i];
        for (j=m->u->StartRow[i]+1;j<m->u->StartRow[i+1];j++)
        { x[i] -= (m->u->a[j])*(x[m->u->col[j]]); }
        x[i] /= m->u->a[m->u->StartRow[i]];
    }
    free(z);
    return;
}


 /**************************************************
            Function to assign branch nodes
  **************************************************/
void Assign_Branch_Nodes( branch *b, double *h )
{
    int n, k;
    double hused;

    n = ((int) ceil((b->plen)/(*h)))+1;
    hused = (b->plen)/((double) n-1);
    b->d = (double *) malloc( n*sizeof(double));
    b->x = (double *) malloc( n*sizeof(double));
    b->x[0] = 0.0;
    for ( k=1 ; k<(n-1) ; k++ ) b->x[k] = ((double) k)*hused;
    b->x[n-1] = b->plen;
    for ( k=0 ; k<n ; k++ ) b->d[k] = b->diam;
    b->nd = n;

    if ( b->child != NULL) Assign_Branch_Nodes( b->child, h);
    if ( b->peer != NULL) Assign_Branch_Nodes( b->peer, h);
}


 /************************************************************
         Function returns primitive uniform random number.
  ************************************************************/
double ran(unsigned int *ix, unsigned int *iy, unsigned int *iz)
{
    double tmp;

/*  1st item of modular arithmetic  */
    *ix = (171*(*ix))%30269;
/*  2nd item of modular arithmetic  */
    *iy = (172*(*iy))%30307;
/*  3rd item of modular arithmetic  */
    *iz = (170*(*iz))%30323;
/*  Generate random number in (0,1) */
    tmp = ((double) (*ix))/30269.0+((double) (*iy))/30307.0
          +((double) (*iz))/30323.0;
    return fmod(tmp,1.0);
}

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