cfiber.py

from neuron import h, gui
import math
import random
#neuron.load_mechanisms("./mod")

class cfiber(object):
    '''
    C-fiber class with parameters:
    L: int (mkM)
        length of compartment
    d: float
        diameter of fiber
    num: int
        number of compartments
    coordinates: dict (updates by position())
        coordinates of each section
    zpozition: int
        z - coordinate for few cells simulation
    fast_diff: bool
        Is there fast diffusion?
          -Yes: True
          -No: False
    diffs: list
        list of diffusion mechanisms (NEURON staff)
    recs: list
        list of receptors mechanisms (NEURON staff)
    '''
    def __init__(self, L, d, zpozition, x_application, fast_diff, numofmodel, temperature = 25):
        self.coordinates = dict()
        self.distances = dict()
        self.diffusions = dict()
        self.fast_diff = fast_diff
        self.diffs = []
        self.recs = []
        self.synlistinh = []
        self.synlistex = []
        self.L = L
        self.diam = d
        self.zpozition = zpozition
        self.x_application = x_application
        self.numofmodel = numofmodel
        if self.numofmodel == 11 or self.numofmodel == 12:
            self.num = 170
        else:
            self.num = 120
        self.create_sections()
        self.build_topology()
        # # self.build_subsets()
        self.define_geometry()
        self.position()
        self.distance()
        self.define_biophysics(temperature)
        self.synapses()

    def create_sections(self):
        '''
        Creates sections (compartments)
        '''
        self.branch = h.Section(name='branch', cell=self)
        self.stimsec = [h.Section(name='stimsec[%d]' % i) for i in range(self.num)]
        self.all_secs = h.SectionList()
        # for sec in self.branch:
        self.all_secs.append(sec=self.branch)
        for sec in self.stimsec:
            self.all_secs.append(sec=sec)

    def build_topology(self):
        '''
        Connects sections
        '''
        self.stimsec[0].connect(self.branch(0), 1)
        if self.numofmodel == 11 or self.numofmodel == 12:
            for i in range(1, 70):
                self.stimsec[i].connect(self.stimsec[i-1])
            for i in range(70, 120):
                self.stimsec[i].connect(self.stimsec[i-1])
            for i in range(120, 170):
                self.stimsec[i].connect(self.stimsec[i-1])
            self.stimsec[70].connect(self.stimsec[69])
            self.stimsec[120].connect(self.stimsec[69])
        else:
            for i in range(1, len(self.stimsec)):
                self.stimsec[i].connect(self.stimsec[i-1])
    def define_geometry(self):
        '''
        Adds length and diameter to sections
        '''
        for sec in self.stimsec:
            sec.L = self.L# microns
            sec.diam = self.diam # microns
            sec.nseg = 3
        self.branch.L = self.L
        self.branch.diam = self.diam
        self.branch.nseg = 1
        h.define_shape() # Translate into 3D points.
    def position(self):
        '''
        Adds 3D position
        '''
        if self.numofmodel == 11 or self.numofmodel == 12:
            # h.pt3dclear()
            # h.pt3dadd(0, 0, self.zpozition, self.diam)
            # h.pt3dadd(self.L, 0, self.zpozition, self.diam)
            xyz = dict(x=self.L, y=0, z=0)
            self.coordinates.update({self.branch: xyz})
            for i in range(70):
                # h.pt3dclear()
                # h.pt3dadd(self.L*(i+1), 0, self.zpozition, self.diam)
                # h.pt3dadd(self.L*(i+2), 0, self.zpozition, self.diam)
                xyz = dict(x=self.L*(i+2), y=0, z=0)
                self.coordinates.update({self.stimsec[i]: xyz})
            for i in range(70, 120):
                # h.pt3dclear()
                # h.pt3dadd(self.L*(i+1), (i-70)*8, self.zpozition, self.diam)
                # h.pt3dadd(self.L*(i+2), (i-69)*8, self.zpozition, self.diam)
                xyz = dict(x=self.L*(i+2), y=(i-69)*8, z=0)
                # self.coordinates.update({self.stimsec[i]: xyz})
            for i in range(120, 170):
                # h.pt3dclear()
                # h.pt3dadd(self.L*(i-49), (i-120)*(-8), self.zpozition, self.diam)
                # h.pt3dadd(self.L*(i-48), (i-119)*(-8), self.zpozition, self.diam)
                xyz = dict(x=self.L*(i-48), y=(i-119)*(-8), z=0)
                self.coordinates.update({self.stimsec[i]: xyz})
        else:
            i = 0
            for sec in self.all_secs:
              # h.pt3dclear()
              # h.pt3dadd(self.L*i, 0, self.zpozition, self.diam)
              # h.pt3dadd(self.L*(i+1), 0, self.zpozition, self.diam)
              xyz = dict(x=self.L*(i+1), y=0, z=0)
              self.coordinates.update({sec: xyz})
              i+=1
    def distance(self):
        '''
        Adds distances from application for every compartment
        '''
        #self.distances.clear()
        if self.numofmodel == 11 or self.numofmodel == 12:
            self.x_application = -400
            for compartment in self.all_secs:
                distance = math.sqrt((30050-self.coordinates.get(compartment).get('x'))**2 + (self.x_application-self.coordinates.get(compartment).get('y'))**2 + (0.01-self.coordinates.get(compartment).get('z'))**2)
                self.distances.update({compartment: distance})
        else:
            for compartment in self.all_secs:
                distance = math.sqrt((self.x_application-self.coordinates.get(compartment).get('x'))**2 + (10-self.coordinates.get(compartment).get('y'))**2 + (0.01-self.coordinates.get(compartment).get('z'))**2)
                self.distances.update({compartment: distance})

    def define_biophysics(self, temperature):
        '''
        Adds channels and their parameters
        '''
        for sec in self.all_secs: # 'all' defined in build_subsets
            sec.Ra = 35  # Axial resistance in Ohm * cm
            sec.cm = 1      # Membrane capacitance in micro Farads / cm^2
            sec.insert('nav1p8')
            sec.insert('nav1p9')
            sec.insert('extrapump')
            sec.insert('koi')
            sec.insert('naoi')
            sec.insert('nakpump')
            sec.insert('nattxs')
            sec.insert('kdr')
            sec.insert('kad')
            sec.insert('kap')
            sec.insert('leak')
            sec.insert('Nav1_3')
            sec.insert('extracellular')
            sec.insert('iKCa')
            sec.insert('iCaAN')
            sec.insert('CaIntraCellDyn')
            if self.numofmodel == 8 or self.numofmodel >= 11:
                sec.gbar_nav1p8 = random.uniform(0.15, 0.25)
                sec.gbar_nav1p9 = 0.00001
            elif self.numofmodel == 7:
                sec.gbar_nav1p8 = 0.1
                sec.gbar_nav1p9 = 0.0001
            else:
                sec.gbar_nav1p8 = 0
                sec.gbar_nav1p9 = 0
            sec.gbar_kdr = 0.01
            sec.gbar_kad = 0.01
            sec.gbar_kap = 0.01
            if self.numofmodel == 6:
                sec.gbar_nattxs = 0.2
            else:
                sec.gbar_nattxs = 0.1
            sec.gbar_Nav1_3 = 0.0#2
            sec.smalla_nakpump = -0.0047891
            sec.theta_naoi = 0.029
            sec.theta_koi = 0.029
            sec.celsiusT_nattxs = temperature
            sec.celsiusT_nav1p8= temperature
            sec.celsiusT_nav1p9= temperature
            sec.celsiusT_nakpump = temperature
            sec.celsiusT_kad = temperature
            sec.celsiusT_kap = temperature
            sec.celsiusT_kdr = temperature
            sec.celsiusT_iKCa = temperature
            sec.gbar_iKCa = 0.001
            # # sec.gnabar_nav11_L263V = 0.5
            sec.depth_CaIntraCellDyn = 0.1
            sec.cai_tau_CaIntraCellDyn = 2.0
            sec.cai_inf_CaIntraCellDyn = 50.0e-6
            sec.gbar_iCaAN = 0.0035
            sec.celsiusT_iCaAN = temperature


        for sec in self.stimsec:
            if self.numofmodel == 13 or self.numofmodel == 14:
                self.add_5HTreceptors(sec, random.randint(10, 20), 3)
            else:
                self.add_P2Xreceptors(sec, 10, 3, temperature)
                # self.add_5HTreceptors(sec, 10, 3)


    def add_P2Xreceptors(self, compartment, time, g, temperature):
        '''
        Adds P2X3 receptors
        Parameters
        ----------
        compartment: section of NEURON cell
            part of neuron
        x: int
            x - coordinate of ATP application
        time: int (ms)
            time of ATP application
        g: float
            receptor conductance
        '''
        if self.fast_diff:
            diff = h.AtP_42(compartment(0.5))
            diff.h = self.distances.get(compartment)
            diff.tx1 = time
            diff.Deff = 0.8
            if self.numofmodel == 4 or self.numofmodel == 5:
                diff.c0cleft = 10
            else:
                diff.c0cleft = 1
            if self.numofmodel == 1:
                diff.k = 0
            elif self.numofmodel == 3:
                diff.k = 0.6
            else:
                diff.k = 0.001
        else:
            diff = h.AtP_slow(compartment(0.5))
            diff.h = self.distances.get(compartment)
            diff.tx1 = time + 0 #+ (diff.h/1250)*1000
            diff.c0cleft = 0.300
        self.diffusions.update({diff: compartment})
        rec = h.p2x3(compartment(0.5))
        rec.gmax = g
        rec.celsiusT = temperature
        rec.Ev = 5
        if self.numofmodel == 4 or self.numofmodel == 5:
            rec2 = h.p2x2(compartment(0.5))
            rec2.Ev = -7
            rec2.gmax = 1
            h.setpointer(diff._ref_atp, 'patp', rec2)
            self.recs.append(rec2)
        if self.numofmodel == 4:
            rec.gmax = 0
        if self.numofmodel == 5:
            rec.gmax = 0.2
            rec2.gmax = 0.2
        h.setpointer(diff._ref_atp, 'patp', rec)
        self.recs.append(rec)
        self.diffs.append(diff)

    def add_5HTreceptors(self, compartment, time, g):
        '''
        Adds 5HT receptors
        Parameters
        ----------
        compartment: section of NEURON cell
            part of neuron
        x: int
            x - coordinate of serotonin application
        time: int (ms)
            time of serotonin application
        g: float
            receptor conductance
        '''
        if self.fast_diff:
            diff = h.diff_5HT(compartment(0.5))
            diff.h = self.distances.get(compartment)
            diff.tx1 = time
            if self.numofmodel == 14:
                diff.a = 10
            else:
                diff.a = 0
            diff.Deff = 0.2
            diff.c0cleft = 3
        else:
            diff = h.slow_5HT(compartment(0.5))
            diff.h = self.distances.get(compartment)
            diff.tx1 = time + 0 + (diff.h/50)*10#00
            diff.c0cleft = 3
        rec = h.r5ht3a(compartment(0.5))
        rec.gmax = g
        h.setpointer(diff._ref_serotonin, 'serotonin', rec)
        self.diffs.append(diff)
        self.recs.append(rec)

    def connect2target(self, target):
        '''
        Adds presynapses
        Parameters
        ----------
        target: NEURON cell
            target neuron
        Returns
        -------
        nc: NEURON NetCon
            connection between neurons
        '''
        nc = h.NetCon(self.branch(1)._ref_v, target, sec = self.branch)
        nc.threshold = 10
        return nc

    def synapses(self):
        '''
        Adds synapses
        '''
        for i in range(10):
            s = h.GABAa_DynSyn(self.branch(0.5)) # Inhibitory
            self.synlistinh.append(s)

            s = h.ExpSyn(self.branch(0.5)) # Excitatory
            s.tau = 0.15
            s.e = 50
            self.synlistex.append(s)