Infraslow intrinsic rhythmogenesis in a subset of AOB projection neurons (Gorin et al 2016)

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Accession:217783
We investigated patterns of spontaneous neuronal activity in mouse accessory olfactory bulb mitral cells, the direct neural link between vomeronasal sensory input and limbic output. Both in vitro and in vivo, we identify a subpopulation of mitral cells that exhibit slow stereotypical rhythmic discharge. In intrinsically rhythmogenic neurons, these periodic activity patterns are maintained in absence of fast synaptic drive. The physiological mechanism underlying mitral cell autorhythmicity involves cyclic activation of three interdependent ionic conductances: subthreshold persistent Na(+) current, R-type Ca(2+) current, and Ca(2+)-activated big conductance K(+) current. Together, the interplay of these distinct conductances triggers infraslow intrinsic oscillations with remarkable periodicity, a default output state likely to affect sensory processing in limbic circuits. The model reproduces the intrinsic firing in a reconstructed single AOB mitral cell with ion channels kinetics fitted to experimental measurements of their steady state and time course.
Reference:
1 . Gorin M, Tsitoura C, Kahan A, Watznauer K, Drose DR, Arts M, Mathar R, O'Connor S, Hanganu-Opatz IL, Ben-Shaul Y, Spehr M (2016) Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons. J Neurosci 36:3127-44 [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: Olfactory bulb;
Cell Type(s): Olfactory bulb (accessory) mitral cell;
Channel(s): I Potassium; I Na,p; I Calcium; I Na,t; I K,Ca; I A; I K; I R;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Sensory processing; Oscillations; Olfaction;
Implementer(s): O'Connor, Simon [simon.oconnor at btinternet.com];
Search NeuronDB for information about:  I Na,p; I Na,t; I A; I K; I K,Ca; I Calcium; I Potassium; I R;
COMMENT

   **************************************************
   File generated by: neuroConstruct v1.7.1 
   **************************************************

   This file holds the implementation in NEURON of the Cell Mechanism:
   NaxSH10_ChannelML (Type: Channel mechanism, Model: ChannelML based process)

   with parameters: 
   /channelml/@units = Physiological Units 
   /channelml/notes = ChannelML file containing a single Channel description 
   /channelml/channel_type/@name = NaxSH10_ChannelML 
   /channelml/channel_type/@density = yes 
   /channelml/channel_type/status/@value = stable 
   /channelml/channel_type/status/comment = Agreement of generated NEURON and GENESIS to original NEURON mod. Compared voltage and n traces on single comp with current pulse 
   /channelml/channel_type/status/contributor/name = Padraig Gleeson 
   /channelml/channel_type/notes = Na Channel 
   /channelml/channel_type/authorList/modelTranslator/name = Padraig Gleeson 
   /channelml/channel_type/authorList/modelTranslator/institution = UCL 
   /channelml/channel_type/authorList/modelTranslator/email = p.gleeson - at - ucl.ac.uk 
   /channelml/channel_type/current_voltage_relation/@cond_law = ohmic 
   /channelml/channel_type/current_voltage_relation/@ion = na 
   /channelml/channel_type/current_voltage_relation/@default_gmax = 40 
   /channelml/channel_type/current_voltage_relation/@default_erev = 67 
   /channelml/channel_type/current_voltage_relation/@charge = 1 
   /channelml/channel_type/current_voltage_relation/q10_settings/@q10_factor = 2 
   /channelml/channel_type/current_voltage_relation/q10_settings/@experimental_temp = 24 
   /channelml/channel_type/current_voltage_relation/gate[1]/@name = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/@instances = 3 
   /channelml/channel_type/current_voltage_relation/gate[1]/closed_state/@id = m0 
   /channelml/channel_type/current_voltage_relation/gate[1]/open_state/@id = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/open_state/@fraction = 1 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@name = alpha 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@from = m0 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@to = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@expr_form = exp_linear 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@rate = 2.880000018 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@scale = 7.2 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@midpoint = -20 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@name = beta 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@from = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@to = m0 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@expr_form = exp_linear 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@rate = 0.892800005 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@scale = -7.2 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@midpoint = -20 
   /channelml/channel_type/current_voltage_relation/gate[1]/time_course/@name = tau 
   /channelml/channel_type/current_voltage_relation/gate[1]/time_course/@from = m0 
   /channelml/channel_type/current_voltage_relation/gate[1]/time_course/@to = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/time_course/@expr_form = generic 
   /channelml/channel_type/current_voltage_relation/gate[1]/time_course/@expr = 1/( (alpha + beta) * temp_adj_m ) < 0.02 ? (0.02 * temp_adj_m) : 1/(alpha + beta) 
   /channelml/channel_type/current_voltage_relation/gate[2]/@name = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/@instances = 1 
   /channelml/channel_type/current_voltage_relation/gate[2]/closed_state/@id = h0 
   /channelml/channel_type/current_voltage_relation/gate[2]/open_state/@id = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/open_state/@fraction = 1 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@name = alpha 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@from = h0 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@to = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@expr_form = exp_linear 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@rate = 0.045 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@scale = 1.5 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[1]/@midpoint = -35 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@name = beta 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@from = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@to = h0 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@expr_form = exp_linear 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@rate = 0.015 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@scale = -1.5 
   /channelml/channel_type/current_voltage_relation/gate[2]/transition[2]/@midpoint = -35 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@name = tau 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@from = h0 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@to = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@expr_form = generic 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@expr = 1/( (alpha + beta) * temp_adj_h ) < 0.5 ? (0.5 * temp_adj_h) : 1/(alpha + beta)   
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@name = inf 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@from = h0 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@to = h 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@expr_form = sigmoid 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@rate = 1 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@scale = 4 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@midpoint = -40 
   /channelml/channel_type/impl_prefs/table_settings/@max_v = 100 
   /channelml/channel_type/impl_prefs/table_settings/@min_v = -100 
   /channelml/channel_type/impl_prefs/table_settings/@table_divisions = 2000 

// File from which this was generated: /home/Simon/NML2_Test/AOB_MC_neuroConstruct/cellMechanisms/NaxSH10_ChannelML/NaChannel.xml

// XSL file with mapping to simulator: /home/Simon/NML2_Test/AOB_MC_neuroConstruct/cellMechanisms/NaxSH10_ChannelML/ChannelML_v1.8.1_NEURONmod.xsl

ENDCOMMENT


?  This is a NEURON mod file generated from a ChannelML file

?  Unit system of original ChannelML file: Physiological Units

COMMENT
    ChannelML file containing a single Channel description
ENDCOMMENT

TITLE Channel: NaxSH10_ChannelML

COMMENT
    Na Channel
ENDCOMMENT


UNITS {
    (mA) = (milliamp)
    (mV) = (millivolt)
    (S) = (siemens)
    (um) = (micrometer)
    (molar) = (1/liter)
    (mM) = (millimolar)
    (l) = (liter)
}


    
NEURON {
      

    SUFFIX NaxSH10_ChannelML
    USEION na READ ena WRITE ina VALENCE 1 ? reversal potential of ion is read, outgoing current is written
           
        
    RANGE gmax, gion
    
    RANGE minf, mtau
    
    RANGE hinf, htau
    
}

PARAMETER { 
      

    gmax = 0.04 (S/cm2)  ? default value, should be overwritten when conductance placed on cell
    
}



ASSIGNED {
      

    v (mV)
    
    celsius (degC)
          

    ? Reversal potential of na
    ena (mV)
    ? The outward flow of ion: na calculated by rate equations...
    ina (mA/cm2)
    
    
    gion (S/cm2)
    minf
    mtau (ms)
    hinf
    htau (ms)
    
}

BREAKPOINT { 
                        
    SOLVE states METHOD cnexp
        
    gion = gmax * ((1*m)
^3) * ((1*h)
^1)      

    ina = gion*(v - ena)
            

}



INITIAL {
    
    ena = 67
        
    rates(v)
    m = minf
        h = hinf
        
    
}
    
STATE {
    m
    h
    
}



DERIVATIVE states {
    rates(v)
    m' = (minf - m)/mtau
            h' = (hinf - h)/htau
            

}

PROCEDURE rates(v(mV)) {  
    
    ? Note: not all of these may be used, depending on the form of rate equations
    LOCAL  alpha, beta, tau, inf, gamma, zeta
, temp_adj_m,
         A_alpha_m, B_alpha_m, Vhalf_alpha_m,
         A_beta_m, B_beta_m, Vhalf_beta_m
, temp_adj_h,
         A_alpha_h, B_alpha_h, Vhalf_alpha_h,
         A_beta_h, B_beta_h, Vhalf_beta_h,
         A_inf_h, B_inf_h, Vhalf_inf_h
    
    TABLE minf, mtau,hinf, htau
 DEPEND celsius FROM -100 TO 100 WITH 2000
    
    UNITSOFF
    
    ? There is a Q10 factor which will alter the tau of the gates 
                 

    temp_adj_m = 2^((celsius - 24)/10)     

    temp_adj_h = 2^((celsius - 24)/10)
            
                
           

        
    ?      ***  Adding rate equations for gate: m  ***
        
    ? Found a parameterised form of rate equation for alpha, using expression: A*((v-Vhalf)/B) / (1 - exp(-((v-Vhalf)/B)))
    A_alpha_m = 2.880000018
    B_alpha_m = 7.2
    Vhalf_alpha_m = -20 
    alpha = A_alpha_m * vtrap((v - Vhalf_alpha_m), B_alpha_m)
    
    
    ? Found a parameterised form of rate equation for beta, using expression: A*((v-Vhalf)/B) / (1 - exp(-((v-Vhalf)/B)))
    A_beta_m = 0.892800005
    B_beta_m = -7.2
    Vhalf_beta_m = -20 
    beta = A_beta_m * vtrap((v - Vhalf_beta_m), B_beta_m)
    
     
    ? Found a generic form of the rate equation for tau, using expression: 1/( (alpha + beta) * temp_adj_m ) < 0.02 ? (0.02 * temp_adj_m) : 1/(alpha + beta)
    
    
    if (1/( (alpha + beta) * temp_adj_m ) < 0.02 ) {
        tau =  (0.02 * temp_adj_m) 
    } else {
        tau =  1/(alpha + beta)
    }
    mtau = tau/temp_adj_m
    minf = alpha/(alpha + beta)
    


    ?     *** Finished rate equations for gate: m ***
    

    
            
                
           

        
    ?      ***  Adding rate equations for gate: h  ***
        
    ? Found a parameterised form of rate equation for alpha, using expression: A*((v-Vhalf)/B) / (1 - exp(-((v-Vhalf)/B)))
    A_alpha_h = 0.045
    B_alpha_h = 1.5
    Vhalf_alpha_h = -35 
    alpha = A_alpha_h * vtrap((v - Vhalf_alpha_h), B_alpha_h)
    
    
    ? Found a parameterised form of rate equation for beta, using expression: A*((v-Vhalf)/B) / (1 - exp(-((v-Vhalf)/B)))
    A_beta_h = 0.015
    B_beta_h = -1.5
    Vhalf_beta_h = -35 
    beta = A_beta_h * vtrap((v - Vhalf_beta_h), B_beta_h)
    
     
    ? Found a generic form of the rate equation for tau, using expression: 1/( (alpha + beta) * temp_adj_h ) < 0.5 ? (0.5 * temp_adj_h) : 1/(alpha + beta)  
    
    
    if (1/( (alpha + beta) * temp_adj_h ) < 0.5 ) {
        tau =  (0.5 * temp_adj_h) 
    } else {
        tau =  1/(alpha + beta)  
    }
    htau = tau/temp_adj_h
    
    ? Found a parameterised form of rate equation for inf, using expression: A / (1 + exp((v-Vhalf)/B))
    A_inf_h = 1
    B_inf_h = 4
    Vhalf_inf_h = -40 
    inf = A_inf_h / (exp((v - Vhalf_inf_h) / B_inf_h) + 1)
    
    hinf = inf
    


    ?     *** Finished rate equations for gate: h ***
    

         

}


? Function to assist with parameterised expressions of type linoid/exp_linear

FUNCTION vtrap(VminV0, B) {
    if (fabs(VminV0/B) < 1e-6) {
    vtrap = (1 + VminV0/B/2)
}else{
    vtrap = (VminV0 / B) /(1 - exp((-1 *VminV0)/B))
    }
}

UNITSON



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