Channel density variability among CA1 neurons (Migliore et al. 2018)

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The peak conductance of many ion channel types measured in any given animal is highly variable across neurons, both within and between neuronal populations. The current view is that this occurs because a neuron needs to adapt its intrinsic electrophysiological properties either to maintain the same operative range in the presence of abnormal inputs or to compensate for the effects of pathological conditions. Limited experimental and modeling evidence suggests this might be implemented via the correlation and/or degeneracy in the function of multiple types of conductances. To study this mechanism in hippocampal CA1 neurons and interneurons, we systematically generated a set of morphologically and biophysically accurate models. We then analyzed the ensembles of peak conductance obtained for each model neuron. The results suggest that the set of conductances expressed in the various neuron types may be divided into two groups: one group is responsible for the major characteristics of the firing behavior in each population and the other more involved with degeneracy. These models provide experimentally testable predictions on the combination and relative proportion of the different conductance types that should be present in hippocampal CA1 pyramidal cells and interneurons.
1 . Migliore R, Lupascu CA, Bologna LL, Romani A, Courcol JD, Antonel S, Van Geit WAH, Thomson AM, Mercer A, Lange S, Falck J, Roessert CA, Shi Y, Hagens O, Pezzoli M, Freund TF, Kali S, Muller EB, Schuermann F, Markram H, Migliore M (2018) The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow PLOS Computational Biology
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: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I h; Ca pump; I K; I K,Ca; I Calcium; I CAN; I M; I Na,t; I A; I_KD; I T low threshold; I L high threshold;
Gap Junctions:
Simulation Environment: NEURON; BluePyOpt ;
Model Concept(s): Activity Patterns; Action Potentials; Detailed Neuronal Models; Methods; Parameter Fitting;
Implementer(s): Migliore, Rosanna [rosanna.migliore at]; Migliore, Michele [Michele.Migliore at];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; I_KD; Ca pump;
cacumm.mod *
cagk.mod *
cal2.mod *
can2.mod *
cat.mod *
kadist.mod *
kaprox.mod *
kdrca1.mod *
kmb.mod *
TITLE Slow Ca-dependent potassium current
                            :   Ca++ dependent K+ current IC responsible for slow AHP
                            :   Differential equations
                            :   Model based on a first order kinetic scheme
                            :       + n cai <->     (alpha,beta)
                            :   Following this model, the activation fct will be half-activated at 
                            :   a concentration of Cai = (beta/alpha)^(1/n) = cac (parameter)
                            :   The mod file is here written for the case n=2 (2 binding sites)
                            :   ---------------------------------------------
                            :   This current models the "slow" IK[Ca] (IAHP): 
                            :      - potassium current
                            :      - activated by intracellular calcium
                            :      - NOT voltage dependent
                            :   A minimal value for the time constant has been added
                            :   Ref: Destexhe et al., J. Neurophysiology 72: 803-818, 1994.
                            :   See also: ,
                            :   modifications by Yiota Poirazi 2001 (
			    :   taumin = 0.5 ms instead of 0.1 ms	

                            NEURON {
                                    SUFFIX kca
                                    USEION k READ ek WRITE ik
                                    USEION ca READ cai
                                    RANGE gk, gbar, m_inf, tau_m,ik
                                    GLOBAL beta, cac

                            UNITS {
                                    (mA) = (milliamp)
                                    (mV) = (millivolt)
                                    (molar) = (1/liter)
                                    (mM) = (millimolar)

                            PARAMETER {
                                    v               (mV)
                                    celsius = 36    (degC)
                                    ek      = -80   (mV)
                                    cai     = 2.4e-5 (mM)           : initial [Ca]i
                                    gbar    = 0.01   (mho/cm2)
                                    beta    = 0.03   (1/ms)          : backward rate constant
                                    cac     = 0.00035  (mM)            : middle point of activation fct
       				    taumin  = 0.5    (ms)            : minimal value of the time cst

                            STATE {m}        : activation variable to be solved in the DEs       

                            ASSIGNED {       : parameters needed to solve DE 
                                    ik      (mA/cm2)
                                    tau_m   (ms)
                            BREAKPOINT { 
                                    SOLVE states METHOD derivimplicit
                                    gk = gbar*m*m*m     : maximum channel conductance
                                    ik = gk*(v - ek)    : potassium current induced by this channel

                            DERIVATIVE states { 
                                    m' = (m_inf - m) / tau_m

                            INITIAL {
                            :  activation kinetics are assumed to be at 22 deg. C
                            :  Q10 is assumed to be 3
                                    tadj = 3 ^ ((celsius-22.0)/10) : temperature-dependent adjastment factor
                                    m = m_inf

                            PROCEDURE evaluate_fct(v(mV),cai(mM)) {  LOCAL car
                                    car = (cai/cac)^4
                                    m_inf = car / ( 1 + car )      : activation steady state value
                                    tau_m =  1 / beta / (1 + car) / tadj
                                    if(tau_m < taumin) { tau_m = taumin }   : activation min value of time cst

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