Burst and tonic firing behaviour in subfornical organ (SFO) neurons (Medlock et al 2018)

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Accession:262422
"Subfornical organ (SFO) neurons exhibit heterogeneity in current expression and spiking behavior, where the two major spiking phenotypes appear as tonic and burst firing. Insight into the mechanisms behind this heterogeneity is critical for understanding how the SFO, a sensory circumventricular organ, integrates and selectively influences physiological function. To integrate efficient methods for studying this heterogeneity, we built a single-compartment, Hodgkin-Huxley-type model of an SFO neuron that is parameterized by SFO-specific in vitro patch-clamp data. The model accounts for the membrane potential distribution and spike train variability of both tonic and burst firing SFO neurons. Analysis of model dynamics confirms that a persistent Na+ and Ca2+ currents are required for burst initiation and maintenance and suggests that a slow-activating K+ current may be responsible for burst termination in SFO neurons. Additionally, the model suggests that heterogeneity in current expression and subsequent influence on spike afterpotential underlie the behavioral differences between tonic and burst firing SFO neurons. Future use of this model in coordination with single neuron patch-clamp electrophysiology provides a platform for explaining and predicting the response of SFO neurons to various combinations of circulating signals, thus elucidating the mechanisms underlying physiological signal integration within the SFO."
Reference:
1 . Medlock L, Shute L, Fry M, Standage D, Ferguson AV (2018) Ionic mechanisms underlying tonic and burst firing behavior in subfornical organ neurons: a combined experimental and modeling study. J Neurophysiol 120:2269-2281 [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): Hodgkin-Huxley neuron;
Channel(s): I Na,t; I Sodium; I Potassium; I Na,p; I Calcium; I A; I_Ks;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: MATLAB;
Model Concept(s): Action Potentials; Simplified Models; Activity Patterns; Bursting;
Implementer(s): Medlock, Laura [laura.medlock at mail.utoronto.ca];
Search NeuronDB for information about:  I Na,p; I Na,t; I A; I Sodium; I Calcium; I Potassium; I_Ks;
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MedlockEtAl2018
readme.html
SFO_burst.png
SFO_model.m
SFO_tonic1.png
SFO_tonic2.png
                            
%% SFO Model

% Burst Firing:
% For values of gNa=150 & gK=100 (in mS/cm^2) we get burst firing,
% gKS ranges from 2-5mS/cm^2 depending on the burst regime (B1 vs B2).

% Tonic Firing:
% Transition burst firing regime to tonic firing by either:
% 1. Increasing gK from 100mS/cm^2 to 280mS/cm^2.
% 2. Increasing gNa from from 150mS/cm^2 to 170mS/cm^2.

clear

%% Time:
dt = 0.01;                % Step Size for Eulers Method
timesec = 30;             % End Time (s)
tfinal = timesec*1000;    % End Time (ms)
Tstep =(0:dt:tfinal);     % Time Array (ms)

%% Initial Values:
V=-60;                    % Membrane Potential (mV)
nA=0;                     % IK Activation
mA=0.35;                  % IKS Activation
hA=0;                     % IKS Inactivation
mKA=0;                    % IA Activation
hKA=0;                    % IA Inactivation
sA=0;                     % INa Activation
kA=0;                     % INa Inactivation
mNaP=0;                   % INaP Activation
hNaP=0;                   % INaP Inactivation
mNCa=0;                   % ICa Activation

%% Cell Properties
% Cell Morphology:
CellSize = 10;                       % Model Cell Diameter in microns
CellArea = 4*pi*((CellSize/2).^2);   % Model Cell Area for Spherical Shape
% Cell Capacitance:
Cr = 5;                              % Real Cell Capacitance in pF
C = (Cr/CellArea)*100;               % Model Capacitance in uF/cm^2
% Cell Resistance:
Rr = 1;                              % Real Cell Resistance in gigaohms
R = (Rr * CellArea)*10;              % Model Cell Resistance in ohms*cm^2
% Reversal Potential (in mV):
Er = -65;                            % Reversal Potential for leak
ENa = 107;                           % Reversal Potential for Na+
EK = -88;                            % Reversal Potential for K+
ENSCC = -35;                         % Reversal Potential for NSCC
ECa = 120;                           % Reversal Potential for Ca2+
% Conductance (in mS/cm^2):
gLeak = (1/R)*1000;                  % Conductance of IL
gK = 100;                            % Conductance of IK
gKS = 3;                             % Conductance of IKS
gA = 3;                              % Conductance of IA
gNa = 150;                           % Conductance of INa
gNaP = 0.13;                         % Conductance of INaP
gNSCC = 0.2;                         % Conductance of INSCC
gCa = 0.3;                           % Conductance of ICa

%% Zeros Vectors
Vm=zeros(1,length(Tstep));
Iz=zeros(1,length(Tstep));
IN=zeros(1,length(Tstep));

%% Looping Code
% Solving differential equations with Eulers method:

tidx=0;
for z=Tstep
    tidx=tidx+1;

%% Injected Current
    % Where 1 pA = 0.3183 uA/cm^2 & 10 pA = 3.18 uA/cm^2
    I=0;

%% Time Constants (in ms):
    tau_nA = 7.2-(6.4/(1+exp((V+28.3)/-19.2)));  % Time Constant for IK activation
    tau_mA = 3000;                               % Time Constant for IKS activation
    tau_hA = 10;                                 % Time Constant for IKS inactivation
    tau_sA = 0.1;                                % Time Constant for INa activation
    tau_kA = 1;                                  % Time Constant for INa inactivation
    tau_mNaP = 5;                                % Time Constant for INaP activation
    tau_hNaP = 50;                               % Time Constant for INaP inactivation
    tau_mNCa = 5;                                % Time Constant for ICa activation
    tau_mKA = 5;                                 % Time Constant for IA activation
    tau_hKA = 30;                                % Time Constant for IA inactivation

%% Current Equations:
  % Potassium Currents:
    % Delayed-rectifier K+ Current (IK):
    nA0=1/(1+exp((V-2)/-8));
    nA = nA + dt*((nA0-nA)/tau_nA);
    IK = gK*nA^4*(V-EK);
    % Slow-activating K+ Current (IKS):
    mA0 = 1/(1+exp((V+44)/-18));
    mA = mA + dt*((mA0-mA)/tau_mA);
    hA0 = 1/(1+exp((V+61)/8));
    hA = hA + dt*((hA0-hA)/tau_hA);
    IKS = gKS*mA^3*hA*(V-EK);
    % Transient K+ Current (IA):
    mKA0 = 1/(1+exp((V+44)/-18));
    mKA = mKA + dt*((mKA0-mKA)/tau_mKA);
    hKA0 = 1/(1+exp((V+61)/8));
    hKA = hKA + dt*((hKA0-hKA)/tau_hKA);
    IA = gA*mKA^3*hKA*(V-EK);
  % Sodium Currents:
    % Transient Na+ Current (INa):
    sA0 = 1/(1+exp((V+31)/-6.11));
    sA = sA + dt*((sA0-sA)/tau_sA);
    kA0 = 1/(1+exp((V+62)/6.15));
    kA = kA + dt*((kA0-kA)/tau_kA);
    INa = gNa*sA^3*kA*(V-ENa);
    % Persisent Na+ Current (INaP):
    mNaP0 = 1/(1+exp((V+55)/-4));
    mNaP = mNaP + dt*((mNaP0-mNaP)/tau_mNaP);
    hNaP0 =1/(1+exp((V+45)/6.1));
    hNaP = hNaP + dt*((hNaP0-hNaP)/tau_hNaP);
    INaP = gNaP*mNaP^3*hNaP*(V-ENa);
  % Calcium Currents:
    % N-Type Ca2+ Current (ICa):
    mNCa0 = 1/(1+exp((V+14)/-5.8));
    mNCa = mNCa + dt*((mNCa0-mNCa)/tau_mNCa);
    ICa = gCa*mNCa^2*(V-ECa);
  % Leak Current (IL):
    IL = gLeak*(V-Er);
  % Non-selective Cation Current (INSCC):
    INSCC = gNSCC*(V-ENSCC);
  % Noise (IN):
    stdnoise = 9;          % Standard Deviation for Noise
    IN=stdnoise*randn;     % Noise Current (Gaussian Distribution)

%% Voltage Calculation:
    V = V + ((dt/C)*(I + IN - IL - INa - IK - INSCC - INaP - IA - ICa - IKS));

%% Voltage Array:
    Vm(tidx)= V;

end

%% Membrane Potential vs Time Plot:
figure('Renderer', 'painters', 'Position', [100 100 1200 500])
sh(1)=subplot(1,1,1);
plot(Tstep,Vm,'k-')
% Figure Settings:
box off
ax = gca;
ax.FontSize = 14; 
xlabel('Time (s)','FontSize',14)
ylabel('Membrane Potential (mV)','FontSize',14)
xt=arrayfun(@num2str,get(gca,'xtick')/1000,'un',0);
set(gca,'xticklabel',xt)

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