Active dendrites shape signaling microdomains in hippocampal neurons (Basak & Narayanan 2018)

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Accession:244848
The spatiotemporal spread of biochemical signals in neurons and other cells regulate signaling specificity, tuning of signal propagation, along with specificity and clustering of adaptive plasticity. Theoretical and experimental studies have demonstrated a critical role for cellular morphology and the topology of signaling networks in regulating this spread. In this study, we add a significantly complex dimension to this narrative by demonstrating that voltage-gated ion channels (A-type Potassium channels and T-type Calcium channels) on the plasma membrane could actively amplify or suppress the strength and spread of downstream signaling components. We employed a multiscale, multicompartmental, morphologically realistic, conductance-based model that accounted for the biophysics of electrical signaling and the biochemistry of calcium handling and downstream enzymatic signaling in a hippocampal pyramidal neuron. We chose the calcium – calmodulin – calcium/calmodulin-dependent protein kinase II (CaMKII) – protein phosphatase 1 (PP1) signaling pathway owing to its critical importance to several forms of neuronal plasticity, and employed physiologically relevant theta-burst stimulation (TBS) or theta-burst pairing (TBP) protocol to initiate a calcium microdomain through NMDAR activation at a synapse.
Reference:
1 . Basak R, Narayanan R (2018) Active dendrites regulate the spatiotemporal spread of signaling microdomains. PLoS Comput Biol 14:e1006485 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite; Synapse; Channel/Receptor; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): Ca pump; I A; I_SERCA; I Calcium; I_K,Na; I h; I Potassium;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Calcium dynamics; Reaction-diffusion; Signaling pathways; Synaptic Plasticity;
Implementer(s): Basak, Reshma [reshmab at iisc.ac.in]; Narayanan, Rishikesh [rishi at iisc.ac.in];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; AMPA; NMDA; I A; I h; I Calcium; I Potassium; I_SERCA; I_K,Na; Ca pump;
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Basak_Narayayanan_2018
Spine1000_sample
readme.txt
apamp.mod
caminmax.mod
car.mod
cat.mod
ghkampa.mod
ghknmda.mod
h.mod
kadist.mod *
kaprox.mod
kdrca1.mod *
modcamechs.mod
na3.mod
nax.mod
vmax.mod
distance.hoc
distance_SD.hoc
Fig_13.hoc
mosinit.hoc
n123.hoc *
ObliquePath.hoc *
oblique-paths.hoc *
Sample_output_Calcium.txt
                            
TITLE Ca R-type channel with medium threshold for activation


COMMENT 
  Kinetics taken from Jeffrey C Magee and Daniel Johnston (1995)
  "Characterization of single voltage-gated Na+ and Ca2+ channels in
  apical dendrites of rat CA1 pyramidal neurons", J. Physiol. 487(1):
  67-90.

Sterratt et al. 2012
http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=144490
ENDCOMMENT

NEURON {
    SUFFIX car
    USEION ca READ cai, cao WRITE ica
    RANGE gmax, m, h
    RANGE minf, hinf, taum, tauh
    GLOBAL q10, taum_exp, z
}

UNITS {
    (molar) = (/liter)
    (mA) = (milliamp)
    (nA) = (nanoamp)
    (mV) = (millivolt)
    (mM) = (millimolar)
    (S) = (siemens)
    (uS) = (microsiemens)
    FARADAY = (faraday) (coulomb)
    R = (k-mole) (joule/degC)
}

PARAMETER {   
    gmax = 0      (S/cm2) <0,1e9> 
    q10  = 3  
    taum_exp = 0.92  (ms)            : experimentally-measured taum
    z = 2                         : valency of Ca ions
}  

STATE {	mO mC hO hC }    

ASSIGNED {               : parameters needed to solve DE
    v       (mV)
    celsius (degC)
    cai     (mM)
    cao     (mM)
	  ica     (mA/cm2)
    minf
    hinf
	  taum    (ms)
    tauh    (ms)
}

BREAKPOINT {
    SOLVE kin METHOD sparse
	ica = gmax*mO*mO*mO*hO*ghkg(v,cai,cao,z)
}

INITIAL { 
    taum = q10^(-(celsius-22(degC))/10(degC))*taum_exp
    tauh = q10^(-(celsius-22(degC))/10(degC))*53(ms)
    SOLVE kin STEADYSTATE sparse    
    ica = gmax*mO*mO*mO*hO*ghkg(v,cai,cao,z)
}

KINETIC kin {
    minf = 1/(1+exp(-(v- 3(mV))/8.3(mV)))
    hinf = 1/(1+exp( (v+39(mV))/9.2(mV)))
    ~ mC <-> mO (minf/taum, (1-minf)/taum)
    ~ hC <-> hO (hinf/tauh, (1-hinf)/tauh)
    CONSERVE mC + mO = 1
    CONSERVE hC + hO = 1
}

FUNCTION ghkg(v(mV), ci(mM), co(mM), z) (mV) {
    LOCAL xi, f, exi, fxi
    f = R*(celsius+273.15)/(z*(1e-3)*FARADAY)
    xi = v/f
    exi = exp(xi)
    if (fabs(xi) < 1e-4) {
        fxi = 1 - xi/2
    }else{
        fxi = xi/(exi - 1)
    }
    ghkg = f*((ci/co)*exi - 1)*fxi
}


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