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Simulations of modulation of HCN channels in L5PCs (Mäki-Marttunen and Mäki-Marttunen, 2022)

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Accession:267293
"... In this work, we build upon existing biophysically detailed models of thick-tufted layer V pyramidal cells and model the effects of over- and under-expression of Ih channels as well as their neuromodulation by dopamine (gain of Ih function) and acetylcholine (loss of Ih function). We show that Ih channels facilitate the action potentials of layer V pyramidal cells in response to proximal dendritic stimulus while they hinder the action potentials in response to distal dendritic stimulus at the apical dendrite. We also show that the inhibitory action of the Ih channels in layer V pyramidal cells is due to the interactions between Ih channels and a hot zone of low voltage-activated Ca2+ channels at the apical dendrite. Our simulations suggest that a combination of Ih-enhancing neuromodulation at the proximal apical dendrite and Ih-inhibiting modulation at the distal apical dendrite can increase the layer V pyramidal excitability more than any of the two neuromodulators alone..."
Reference:
1 . Mäki-Marttunen T, Mäki-Marttunen V (2022) Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells Plos Comp Biol [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 layer 5 pyramidal cell;
Channel(s):
Gap Junctions:
Receptor(s): AMPA; NMDA; Gaba;
Gene(s):
Transmitter(s): Acetylcholine; Dopamine; Glutamate; Gaba;
Simulation Environment: NEURON;
Model Concept(s): Neuromodulation;
Implementer(s): Maki-Marttunen, Tuomo [tuomomm at uio.no];
Search NeuronDB for information about:  AMPA; NMDA; Gaba; Acetylcholine; Dopamine; Gaba; Glutamate;
import math
import copy
import pylab

def spike_times(time,vrec,V_min_peak=-20,V_max_valley=0):
  valley_reached = 1
  sptime = []  
  for j in range(1,len(time)-1):
    if valley_reached and vrec[j] >= V_min_peak and vrec[j] > vrec[j-1] and vrec[j] >= vrec[j+1]:
      valley_reached = 0
      sptime.append(time[j])
    elif valley_reached==False and vrec[j] <= V_max_valley:
      valley_reached = 1
  return sptime  

#membpotderivs(time,vrec): Given the membrane potentials (vrec) at time points time[0],time[1],...,time[N-1],
#return the derivatives at time points time[1],time[2],...,time[N-3]
def membpotderivs(time,vrec):
  N = len(time)
  tdiff = [x-y for x,y in zip(time[1:N-1],time[0:N-2])]
  vdiff = [x-y for x,y in zip(vrec[1:N-1],vrec[0:N-2])]
  mderiv = [x/y for x,y in zip(vdiff,tdiff)]
  return [0.5*(x+y) for x,y in zip(mderiv[1:N-2],mderiv[0:N-3])]

#limitcyclescaledv(v1,dv1,v2,dv2): Give the coefficient for memb. pot. derivative that one has to use in order to make
#the difference on the derivative axis as significant as the difference on the memb. pot. axis
def limitcyclescaledv(v1,dv1,v2,dv2):
  maxv = max(max(v1),max(v2))
  minv = min(min(v1),min(v2))
  maxdv = max(max(dv1),max(dv2))
  mindv = min(min(dv1),min(dv2))
  return 1.0*(maxv-minv)/(maxdv-mindv)

def limitcyclediff(v1,dv1,v2,dv2,dvcoeff=0.1):
  N1 = len(v1)
  N2 = len(v2)
  dv1 = [dvcoeff*x for x in dv1]
  dv2 = [dvcoeff*x for x in dv2]
  Dmin = N1*[0]
  for i in range(0,N1):
    Dmin[i] = math.sqrt(min([(x-v1[i])**2+(y-dv1[i])**2 for x,y in zip(v2,dv2)]))
  vdiff = [x-y for x,y in zip(v1[1:N1],v1[0:N1-1])] 
  dvdiff = [x-y for x,y in zip(dv1[1:N1],dv1[0:N1-1])] 
  h = [math.sqrt(x**2+y**2) for x,y in zip(vdiff,dvdiff)]
  #use the trapezoid rule for integration:
  Dminmean = [(x+y)/2.0 for x,y in zip(Dmin[1:N1],Dmin[0:N1-1])]
  #print "hsum="+str(sum(h))
  return sum([x*y for x,y in zip(Dminmean,h)])
  

def interpolate(tref,vref,tint): #Assumes that the trefs come sorted!
  vint = len(tint)*[0.0]
  addedOne = False
  #print tref
  #print tint
  #if tref[len(tref)-1] == tint[len(tint)-1]:
  #  tref.append(tref[len(tref)-1]+0.0001)
  #  vref.append(vref[len(tref)-1])
  #  addedOne = True
  if tref[0] > tint[0] or tref[len(tref)-1] < tint[len(tint)-1]:
    print("Extrapolation needed!")
    return len(tint)*[-1]
  indvrecnow = 0  
  for j in range(0,len(tint)):
    while tref[indvrecnow+1] <= tint[j]:
      indvrecnow = indvrecnow + 1
      if indvrecnow == len(tref)-1: # It must be the last index if this happens
        vint[j:len(tint)] = [vref[indvrecnow]]*(len(tint)-j)
        return vint
    vint[j] = vref[indvrecnow] + 1.0*(tint[j]-tref[indvrecnow])/(tref[indvrecnow+1]-tref[indvrecnow])*(vref[indvrecnow+1]-vref[indvrecnow])
  return vint

def interpolate_extrapolate_constant(tref,vref,tint): #Assumes that the trefs come sorted!
  vint = len(tint)*[0.0]
  addedOne = False
  #print tref
  #print tint
  #if tref[len(tref)-1] == tint[len(tint)-1]:
  #  tref.append(tref[len(tref)-1]+0.0001)
  #  vref.append(vref[len(tref)-1])
  #  addedOne = True

  indvrecnow = 0  
  for j in range(0,len(tint)):
    if tint[j] < tref[0]:
      vint[j] = vref[0]
      continue
    if indvrecnow >= len(tref) - 1:
      vint[j] = vref[-1]
    while tref[indvrecnow+1] <= tint[j]:
      indvrecnow = indvrecnow + 1
      if indvrecnow == len(tref)-1: # It must be the last index if this happens
        vint[j:len(tint)] = [vref[indvrecnow]]*(len(tint)-j)
        return vint
    vint[j] = vref[indvrecnow] + 1.0*(tint[j]-tref[indvrecnow])/(tref[indvrecnow+1]-tref[indvrecnow])*(vref[indvrecnow+1]-vref[indvrecnow])
  return vint

#kronecker product of list A and list B
def kron(A,B):
  C = []
  if type(B[0]) is int or type(B[0]) is float:
    for i in range(0,len(A)):
      for j in range(0,len(B)):
        print("asdf")
        print((B[j]))
        C.append(A[i]*B[j])
  elif type(B[0][0]) is int or type(B[0][0]) is float:
    for i in range(0,len(A)):
      for j in range(0,len(B)):
        C.append([x*A[i] for x in B[j]])
  return C
  
def cumprod(A):
  B = len(A)*[0]; B[0]=A[0]
  for j in range(1,len(A)):
    B[j] = B[j-1]*A[j]
  return B

def oscillatorypoissontimeseries(N, minfreq, maxfreq, oscfreq, phase, T, isprinted=0):
  a = 0.5*(minfreq + maxfreq)
  b = 0.5*(maxfreq - minfreq)
  meanT = 1.0/a
  omega = 2*pylab.pi*oscfreq
  sptime = pylab.zeros([int(0.001*2*T*N/meanT)+100,2],dtype='d')
  #sptime = []
  Nplaced = 0
  for iN in range(0,N):
    t = 0
    while t < T:
      e = pylab.log(1-pylab.rand()) 
      Ttrial = meanT #Ttrial in sec, t and T in msec
      # Newton's method:
      for iter in range(0,50):
        Ttrialold = Ttrial
        Ttrial = Ttrial - (e + a*Ttrial - b/omega*(pylab.cos(omega*(0.001*t+Ttrial)+phase)-pylab.cos(omega*0.001*t+phase))) / (a + b*pylab.sin(omega*(0.001*t+Ttrial)+phase))
      myerr = abs(e + a*Ttrial - b/omega*(pylab.cos(omega*(0.001*t+Ttrial)+phase)-pylab.cos(omega*0.001*t+phase)))
      if Ttrial < 0 or myerr > 0.0001:
        Ttrial = meanT
        # If Newton's method didn't give good result, try fixed point method: Find T such that -aT+b/omega(pylab.cos(omega*t+phase)-pylab.cos(phase)) = pylab.log(1-x):
        for iter in range(0,30000):
          Ttrial = (b/omega*(pylab.cos(omega*(0.001*t+Ttrial)+phase)-pylab.cos(omega*0.001*t+phase)) - e)/a
        Ttrialold = Ttrial
        Ttrial = (b/omega*(pylab.cos(omega*(0.001*t+Ttrial)+phase)-pylab.cos(omega*0.001*t+phase)) - e)/a
      if isprinted > 1:
        print(('iN='+str(iN)+', Err(Ttrial) = '+str(abs(Ttrial-Ttrialold))+', Ttrial = '+str(Ttrial)+', t = '+str(t)+', newPhase='+str(omega*(t/1000+Ttrial)+phase)+', myerr='+str(myerr)))
      t = t+Ttrial*1000
      sptime[Nplaced,:] = [iN,t]
      #sptime.append([iN,t])
      Nplaced = Nplaced + 1
    if isprinted > 0:
      print(('spikes for iN='+str(iN)+' complete'))
  sptime = sptime[:Nplaced,:]
  if isprinted > 0:
    print((str(Nplaced)+' spikes in total, '+str(int(0.001*2*T*N/meanT)+100)+' reserved'))
  return sptime

def printlistlen(A):
  #TODO: recursive method might work out but needs some thought...
  #toCheck = A
  #lens = [len(x) for x in A]
  #levels = [0 for x in A]
  #while type(toCheck) is list and len(toCheck) > 0:
  #  while type(toCheck[0]) is list and len(toCheck[0]) > 0:
  #    toCheck.append(toCheck[0][0])
  #    lens.append[len
  #    toCheck[0].pop(0)
  nan = -1
  if type(A) is list:
   B = copy.deepcopy(A)
   listFound0 = False
   for i0 in range(0,len(B)):
    if type(B[i0]) is list:
     listFound0 = True
     listFound1 = False
     for i1 in range(0,len(B[i0])):
      if type(B[i0][i1]) is list:
       listFound1 = True
       listFound2 = False
       for i2 in range(0,len(B[i0][i1])):
        if type(B[i0][i1][i2]) is list:
         listFound2 = True
         listFound3 = False
         for i3 in range(0,len(B[i0][i1][i2])):
          if type(B[i0][i1][i2][i3]) is list:
           listFound3 = True
           listFound4 = False
           for i4 in range(0,len(B[i0][i1][i2][i3])):
            if type(B[i0][i1][i2][i3][i4]) is list:
             listFound4 = True
             listFound5 = False
             for i5 in range(0,len(B[i0][i1][i2][i3][i4])):
              if type(B[i0][i1][i2][i3][i4][i5]) is list:
               listFound5 = True
               listFound6 = False               
               for i6 in range(0,len(B[i0][i1][i2][i3][i4][i5])):
                if type(B[i0][i1][i2][i3][i4][i5][i6]) is list:
                  listFound6 = True
                  B[i0][i1][i2][i3][i4][i5][i6] = len(B[i0][i1][i2][i3][i4][i5][i6])
                else:
                  B[i0][i1][i2][i3][i4][i5][i6] = nan
               if not listFound6:
                 B[i0][i1][i2][i3][i4][i5] = len(B[i0][i1][i2][i3][i4][i5])
              else:
                B[i0][i1][i2][i3][i4][i5] = nan
             if not listFound5:
               B[i0][i1][i2][i3][i4] = len(B[i0][i1][i2][i3][i4])
            else:
              B[i0][i1][i2][i3][i4] = nan
           if not listFound4:
             B[i0][i1][i2][i3] = len(B[i0][i1][i2][i3])
          else:
            B[i0][i1][i2][i3] = nan
         if not listFound3:
           B[i0][i1][i2] = len(B[i0][i1][i2])
        else:
          B[i0][i1][i2] = nan
       if not listFound2:
         B[i0][i1] = len(B[i0][i1])
      else:
        B[i0][i1] = nan
     if not listFound1:
       B[i0] = len(B[i0])
    else:
      B[i0] = nan
   if not listFound0:
     B = len(B)
  else:
   B = nan
  print(B)

def drawarrow(ax,x,y,acoeff=1,prc=0.9,lw=1,lc='#000000'):
  d = [x[1]-x[0], y[1]-y[0]];
  k = pylab.sqrt(d[0]**2 + d[1]**2)
  d = d/k

  dperp = [acoeff*z for z in [-d[1], d[0]]];
  lens = k-k*(1-prc);
  perplen = 0.5*k*(1-prc);

  px = [x[0],x[1],x[0]+lens*d[0]+perplen*dperp[0],x[0]+lens*d[0]-perplen*dperp[0]];
  py = [y[0],y[1],y[0]+lens*d[1]+perplen*dperp[1],y[0]+lens*d[1]-perplen*dperp[1]];

  px = [px[0],px[1],px[2],px[1],px[3]]
  py = [py[0],py[1],py[2],py[1],py[3]]
  #px = reshape([px(:,[1 2 3 2 4]) nan(size(x,1),1)]',size(x,1)*6,1);
  #py = reshape([py(:,[1 2 3 2 4]) nan(size(x,1),1)]',size(x,1)*6,1);
  ax.plot(px,py,'k-',linewidth=lw,color=lc)

def timeseriesmean(times,x):
  return 1.0*sum([(t2-t1)*(x1+x2)/2 for t1,t2,x1,x2 in zip(times[0:-1],times[1:],x[0:-1],x[1:])])/(times[-1]-times[0])

def timeseriessecondmoment(times,x):
  return 1.0*sum([(t2-t1)*(x1**2+x2**2)/2 for t1,t2,x1,x2 in zip(times[0:-1],times[1:],x[0:-1],x[1:])])

def timeseriesstd(times,x,xmean=pylab.nan):
  if pylab.isnan(xmean):
    xmean = timeseriesmean(times,x)
  return pylab.sqrt(1.0*sum([(t2-t1)*((x1-xmean)**2+(x2-xmean)**2)/2 for t1,t2,x1,x2 in zip(times[0:-1],times[1:],x[0:-1],x[1:])])/(times[-1]-times[0]))

def drawdiscontinuity(ax,y,yoffset,x=0,xoffset=0.1,lw=2.0,lw2=1.0):
  thisline = ax.plot([x-xoffset,x+xoffset],[y-yoffset,y],'k-',linewidth=lw2)
  thisline[0].set_clip_on(False)
  thisline = ax.plot([x-xoffset,x+xoffset],[y,y+yoffset],'k-',linewidth=lw2)
  thisline[0].set_clip_on(False)
  thisline = ax.plot([x-xoffset,x+xoffset],[y-0.5*yoffset,y+0.5*yoffset],'k-',color='#FFFFFF',zorder=100,linewidth=lw)
  thisline[0].set_clip_on(False)

def firingratecurve(spikes,T=[],dt=1.0,gauss_std=5.0):
  if type(spikes) is list:
    spikes = pylab.array(spikes)
  if type(T) is list and len(T) == 0:
    T = max(spikes[0,:])
  FRs = pylab.zeros([int(T/dt),1])
  FRts = [dt*(i+0.5) for i in range(0,len(FRs))]
  for iFRt in range(0,len(FRs)):
    FRs[iFRt] = sum(pylab.exp(-1/2*(FRts[iFRt]-spikes[0,:])**2/gauss_std**2))
  return [FRs,FRts]

def find(condition):
    "Return the indices where ravel(condition) is true"
    res, = np.nonzero(np.ravel(condition))
    return res

def mylegend(fig,pos,styles,texts,nx=1,dx=2,yplus=0.5,yplustext=0.35,colors=[],dashes=[],linewidths=[],myfontsize=8):
  ny = int(pylab.ceil(1.0*len(styles)/nx))
  print("ny = "+str(ny))
  axnew = fig.add_axes(pos)
  handles = []
  for i in range(0,len(styles)):
    handles.append(axnew.plot([dx*int(i/ny)+0.15,dx*int(i/ny)+0.35],[yplus+ny-1-(i%ny),yplus+ny-1-(i%ny)],styles[i]))
    axnew.text(dx*int(i/ny)+0.5,yplustext+ny-1-(i%ny),texts[i],fontsize=myfontsize)
  axnew.set_xlim([0,dx*nx])
  axnew.set_ylim([0,len(styles)])
  for i in range(0,len(dashes)):
    if len(dashes[i]) > 0:
      handles[i][0].set_dashes(dashes[i])
  for i in range(0,len(colors)):
    if len(colors[i]) > 0:
      handles[i][0].set_color(colors[i])
  for i in range(0,len(linewidths)):
    if type(linewidths[i]) is not list and linewidths[i] > 0:
      handles[i][0].set_linewidth(linewidths[i])
  axnew.get_xaxis().set_visible(False)
  axnew.get_yaxis().set_visible(False)
  axnew.set_xlim([0,dx*nx])
  axnew.set_ylim([0,ny])
  return axnew

import math

def colorsredtolila(N,brightness=1.0,whiteness=0.0):
  if N==1:
    return ['#0000FF']
  C = colorsredtolilaint(N,brightness,whiteness)
  hexlist = []
  for j in range(0,N):
    myhex = '#'
    for k in range(0,3):
      if C[j][k] < 16:
        myhex = myhex + '0' + hex(C[j][k])[2]
      else:
        myhex = myhex + hex(C[j][k])[2:4]
    hexlist.append(myhex)
  return hexlist

def colorsredtolilaint(N,brightness=1.0,whiteness=0.0):

  linchange = [1.0/(N-1)*x for x in range(0,N)]
  linchange_x = [x/0.8 for x in [0.0, 0.36, 0.45, 0.65, 0.7, 0.8]]
  linchange_y = [0.0, 0.29, 0.46, 0.65, 0.75, 0.83]
  for i in range(0,len(linchange)):
    ind = N
    for j in range(0,len(linchange_x)):
      if linchange[i] >= linchange_x[j]:
        ind = j
    if ind < len(linchange_x)-1:
      linchange[i] = linchange_y[ind]+(linchange_y[ind+1]-linchange_y[ind])*(linchange[i]-linchange_x[ind])/(linchange_x[ind+1]-linchange_x[ind])

  C = hsv2rgblist([int(255*x) for x in linchange],[1.0-whiteness]*N,[brightness]*N);
  return C


def hsv2rgblist(h, s, v):
  hs = []
  ss = []
  vs = []
  for i in range(0,len(h)):
    h1, s1, v1 = hsv2rgb(h[i],s[i],v[i])
    hs.append(h1)
    ss.append(s1)
    vs.append(v1)
  return list(zip(hs,ss,vs))

def hsv2rgb(h, s, v):
  h = float(h)
  s = float(s)
  v = float(v)
  h60 = h / 60.0
  h60f = math.floor(h60)
  hi = int(h60f) % 6
  f = h60 - h60f
  p = v * (1 - s)
  q = v * (1 - f * s)
  t = v * (1 - (1 - f) * s)
  r, g, b = 0, 0, 0
  if hi == 0: r, g, b = v, t, p
  elif hi == 1: r, g, b = q, v, p
  elif hi == 2: r, g, b = p, v, t
  elif hi == 3: r, g, b = p, q, v
  elif hi == 4: r, g, b = t, p, v
  elif hi == 5: r, g, b = v, p, q
  r, g, b = int(r * 255), int(g * 255), int(b * 255)
  return r, g, b
    
def rgb2hsv(r, g, b):
  r, g, b = r/255.0, g/255.0, b/255.0
  mx = max(r, g, b)
  mn = min(r, g, b)
  df = mx-mn
  if mx == mn:
    h = 0
  elif mx == r:
    h = (60 * ((g-b)/df) + 360) % 360
  elif mx == g:
    h = (60 * ((b-r)/df) + 120) % 360
  elif mx == b:
    h = (60 * ((r-g)/df) + 240) % 360
  if mx == 0:
    s = 0
  else:
    s = df/mx
  v = mx
  return h, s, v

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