Thank you for your reply,and I do need your help.I recreate the model based on Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
https://senselab.med.yale.edu/ModelDB/S ... 123815,but I added chloride accumulation mechanism to study the effect of the decrease of gabaa current on the depolarization of pyramidal neuron
,so now my gabaa.mod as below:
TITLE GABAergic conductance with changing Cl- concentration
NEURON {
POINT_PROCESS gaba
USEION cl READ ecl WRITE icl VALENCE -1
NONSPECIFIC_CURRENT ihco3
RANGE tau1, tau2, g
RANGE P, HCO3e, HCO3i, i
RANGE icl, ihco3, ehco3, e
GLOBAL total
}
UNITS {
(mA) = (milliamp)
(nA) = (nanoamp)
(mV) = (millivolt)
(uS) = (micromho)
(mM) = (milli/liter)
F = (faraday) (coulombs)
R = (k-mole) (joule/degC)
}
PARAMETER {
tau1 =.1 (ms) <1e-9,1e9>
tau2 = 10 (ms) <1e-9,1e9>
HCO3e = 23 (mM) : extracellular HCO3- concentration
HCO3i = 12 (mM) : intracellular HCO3- concentration
P = 0.18 : HCO3/Cl relative permeability
celsius = 37 (degC)
}
ASSIGNED {
v (mV) : postsynaptic voltage
icl (nA) : chloride current = (1-P)*g*(v - ecl)
ihco3 (nA) : bicarb current = P*g*(v - ehco3)
i (nA) : total current generated by this mechanism
: = icl + ihco3
g (uS) : total conductance, split between bicarb (P*g)
: and chloride ((1-P)*g)
factor
total (uS)
ecl (mV) : equilibrium potential for Cl-
ehco3 (mV) : equilibrium potential for HCO3-
e (mV) : reversal potential for GABAR
}
STATE {
A (uS)
B (uS)
}
INITIAL {
LOCAL tp
total = 0
if (tau1/tau2 > .9999) {
tau1 = .9999*tau2
}
A = 0
B = 0
tp = (tau1*tau2)/(tau2 - tau1) * log(tau2/tau1)
factor = -exp(-tp/tau1) + exp(-tp/tau2)
factor = 1/factor
ehco3 = log(HCO3i/HCO3e)*(1000)*(celsius + 273.15)*R/F
e = P*ehco3 + (1-P)*ecl
}
BREAKPOINT {
SOLVE state METHOD cnexp
g = B - A
icl = (1-P)*g*(v-ecl)
ihco3 = P*g*(v-ehco3)
i = icl + ihco3
e = P*ehco3 + (1-P)*ecl
}
DERIVATIVE state {
A' = -A/tau1
B' = -B/tau2
}
NET_RECEIVE(weight (uS)) {
A = A + weight*factor
B = B + weight*factor
total = total+weight
And my chloride accumulation mechanism as below:
NEURON {
SUFFIX cldifus
USEION cl READ icl WRITE cli, ecl VALENCE -1
USEION hco3 READ hco3i, hco3o VALENCE -1
GLOBAL vrat :vrat must be GLOBAL
RANGE tau, cli0, clo0, egaba, delta_egaba, init_egaba, ehco3, ecl
}
DEFINE Nannuli 11
UNITS {
(molar) = (1/liter)
(mM) = (millimolar)
(um) = (micron)
(mA) = (milliamp)
(mV) = (millivolt)
FARADAY = (faraday) (10000 coulomb)
PI = (pi) (1)
F = (faraday) (coulombs)
R = (k-mole) (joule/degC)
}
PARAMETER {
DCl = 2 (um2/ms) : Kuner & Augustine, Neuron 27: 447
tau = 3000 (ms)
cli0 = 4.25 (mM)
clo0 = 135 (mM)
hco3i0 = 12 (mM)
hco3o0 = 23(mM)
P = 0.18
celsius = 37 (degC)
}
ASSIGNED {
diam (um)
icl (mA/cm2)
cli (mM)
hco3i (mM)
hco3o (mM)
vrat[Nannuli] : numeric value of vrat
equals the volume
: of annulus i of a 1um diameter cylinder
: multiply by diam^2 to get volume per um length
egaba (mV)
ehco3 (mV)
ecl (mV)
init_egaba (mV)
delta_egaba (mV)
}
STATE {
: cl[0] is equivalent to cli
: cl[] are very small, so specify absolute tolerance
cl[Nannuli] (mM) <1e-10>
}
BREAKPOINT {
SOLVE state METHOD sparse
ecl = log(cli/clo0)*(1000)*(celsius + 273.15)*R/F
egaba = P*ehco3 + (1-P)*ecl
delta_egaba = egaba - init_egaba
}
LOCAL factors_done
INITIAL {
if (factors_done == 0) { : flag becomes 1 in the first segment
factors_done = 1 : all subsequent segments will have
factors() : vrat = 0 unless vrat is GLOBAL
}
cli = cli0
hco3i = hco3i0
hco3o = hco3o0
FROM i=0 TO Nannuli-1 {
cl = cli
}
ehco3 = log(hco3i/hco3o)*(1000)*(celsius + 273.15)*R/F
ecl = log(cli/clo0)*(1000)*(celsius + 273.15)*R/F
egaba = P*ehco3 + (1-P)*ecl
init_egaba = egaba
delta_egaba = egaba - init_egaba
}
LOCAL frat[Nannuli] : scales the rate constants for model geometry
PROCEDURE factors() {
LOCAL r, dr2
r = 1/2 : starts at edge (half diam), diam = 1, length = 1
dr2 = r/(Nannuli-1)/2 : full thickness of outermost annulus,
: half thickness of all other annuli
vrat[0] = 0
frat[0] = 2*r : = diam
FROM i=0 TO Nannuli-2 {
vrat = vrat + PI*(r-dr2/2)*2*dr2 : interior half
r = r - dr2
frat[i+1] = 2*PI*r/(2*dr2) : outer radius of annulus Ai+1/delta_r=2PI*r*1/delta_r
: div by distance between centers
r = r - dr2
vrat[i+1] = PI*(r+dr2/2)*2*dr2 : outer half of annulus
}
}
KINETIC state {
COMPARTMENT i, diam*diam*vrat {cl}
LONGITUDINAL_DIFFUSION i, DCl*diam*diam*vrat {cl}
~ cl[0] << ((icl*PI*diam/FARADAY) + (diam*diam*vrat[0]*(cli0 - cl[0])/tau)) : icl is Cl- influx
FROM i=0 TO Nannuli-2 {
~ cl <-> cl[i+1] (DCl*frat[i+1], DCl*frat[i+1])
}
cli = cl[0]
}