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:
   BK_IAMC_ChannelML (Type: Channel mechanism, Model: ChannelML based process)

   with parameters: 
   /channelml/@units = SI Units 
   /channelml/notes = A channel from Maex, R and De Schutter, E. Synchronization of Golgi and Granule Cell Firing in a     Detailed Network Model of the Cerebellar Granule  ... 
   /channelml/channel_type/@name = BK_IAMC_ChannelML 
   /channelml/channel_type/status/@value = stable 
   /channelml/channel_type/status/issue = This ChannelML file is intended ONLY to replicate the original GENESIS functionality. A new Granule cell model is being developed based on 	  D'Angelo ... 
   /channelml/channel_type/status/contributor/name = Padraig Gleeson 
   /channelml/channel_type/notes = Calcium dependent K+ channel 
   /channelml/channel_type/authorList/modelAuthor[1]/name = Maex, R. 
   /channelml/channel_type/authorList/modelAuthor[2]/name = De Schutter, E. 
   /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/publication/fullTitle = Maex, R and De Schutter, E. 	Synchronization of Golgi and Granule Cell Firing in a Detailed Network Model of the 	cerebellar Granule Cell Layer. J Neu ... 
   /channelml/channel_type/publication/pubmedRef = http://www.ncbi.nlm.nih.gov/pubmed/9819260 
   /channelml/channel_type/neuronDBref/modelName = K channels 
   /channelml/channel_type/neuronDBref/uri = http://senselab.med.yale.edu/senselab/NeuronDB/channelGene2.htm#table3 
   /channelml/channel_type/current_voltage_relation/@cond_law = ohmic 
   /channelml/channel_type/current_voltage_relation/@ion = k 
   /channelml/channel_type/current_voltage_relation/@default_gmax = 0.15 
   /channelml/channel_type/current_voltage_relation/@default_erev = -0.0865 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@name = Calcium 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@ion = ca 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@charge = 2 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@variable_name = ca_conc 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@min_conc = 7.55e-7 
   /channelml/channel_type/current_voltage_relation/conc_dependence/@max_conc = 0.050 
   /channelml/channel_type/current_voltage_relation/q10_settings/@q10_factor = 3 
   /channelml/channel_type/current_voltage_relation/q10_settings/@experimental_temp = 17.350264793 
   /channelml/channel_type/current_voltage_relation/offset/@value = 0.010 
   /channelml/channel_type/current_voltage_relation/gate[1]/@name = m 
   /channelml/channel_type/current_voltage_relation/gate[1]/@instances = 1 
   /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]/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 = generic 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[1]/@expr = 2500/(1 + ( (1.5e-3 *(exp (-85*v))) / ca_conc)) 
   /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 = generic 
   /channelml/channel_type/current_voltage_relation/gate[1]/transition[2]/@expr = 1500/(1 + (ca_conc / (1.5e-4 * (exp (-77*v))))) 
   /channelml/channel_type/current_voltage_relation/gate[2]/@name = n 
   /channelml/channel_type/current_voltage_relation/gate[2]/@instances = 1 
   /channelml/channel_type/current_voltage_relation/gate[2]/closed_state/@id = n0 
   /channelml/channel_type/current_voltage_relation/gate[2]/open_state/@id = n 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@name = tau 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@from = n0 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@to = n 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@expr_form = generic 
   /channelml/channel_type/current_voltage_relation/gate[2]/time_course/@expr = 0.005 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@name = inf 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@from = n0 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@to = n 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@expr_form = generic 
   /channelml/channel_type/current_voltage_relation/gate[2]/steady_state/@expr = 1 

// File from which this was generated: /home/Simon/NML2_Test/AOB_MC_neuroConstruct/cellMechanisms/BK_IAMC_ChannelML/KCa_chan.xml

// XSL file with mapping to simulator: /home/Simon/NML2_Test/AOB_MC_neuroConstruct/cellMechanisms/BK_IAMC_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: SI Units

COMMENT
    A channel from Maex, R and De Schutter, E. Synchronization of Golgi and Granule Cell Firing in a
    Detailed Network Model of the Cerebellar Granule Cell Layer
ENDCOMMENT

TITLE Channel: BK_IAMC_ChannelML

COMMENT
    Calcium dependent K+ channel
ENDCOMMENT


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


    
NEURON {
      

    SUFFIX BK_IAMC_ChannelML
    USEION k READ ek WRITE ik VALENCE 1  ? reversal potential of ion is read, outgoing current is written
           
        
    USEION ca READ cai VALENCE 2 ? internal concentration of ion is read

    
    RANGE gmax, gion
    
    RANGE minf, mtau
    
    RANGE ninf, ntau
    
}

PARAMETER { 
      

    gmax = 0.000014999999999999999 (S/cm2)  ? default value, should be overwritten when conductance placed on cell
    
}



ASSIGNED {
      

    v (mV)
    
    celsius (degC)
          

    ? Reversal potential of k
    ek (mV)
    ? The outward flow of ion: k calculated by rate equations...
    ik (mA/cm2)
          

    ? The internal concentration of ion: ca is used in the rate equations...
    cai (mM)   
    
    
    gion (S/cm2)
    minf
    mtau (ms)
    ninf
    ntau (ms)
    
}

BREAKPOINT { 
    SOLVE states METHOD derivimplicit
    gion = gmax * (m
^1) * (n
^1)      

    ik = gion*(v - ek)
            

}



INITIAL {
    
    ek = -86.5
        
    settables(v,cai)
    m = minf
        n = ninf
        
    
}
    
STATE {
    m
    n
    
}



DERIVATIVE states {
    settables(v,cai)
    m' = (minf - m)/mtau
            n' = (ninf - n)/ntau
            

}

PROCEDURE settables(v(mV), cai(mM)) {  
    
    ? Note: not all of these may be used, depending on the form of rate equations
    LOCAL  alpha, beta, tau, inf, gamma, zeta, ca_conc
, temp_adj_m
, temp_adj_n
    
    UNITSOFF
    
    ? There is a Q10 factor which will alter the tau of the gates 
                 

    temp_adj_m = 3^((celsius - 17.350264793)/10)     

    temp_adj_n = 3^((celsius - 17.350264793)/10)
    
    ? There is a voltage offset of 0.010. This will shift the dependency of the rate equations 
    v = v - (10)
    
    ? Gate depends on the concentration of ca
    ca_conc = cai ? In NEURON, the variable for the concentration  of ca is cai
    
            
                
           

        
    ?      ***  Adding rate equations for gate: m  ***
         
    ? Found a generic form of the rate equation for alpha, using expression: 2500/(1 + ( (1.5e-3 *(exp (-85*v))) / ca_conc))
    
    ? Note: Equation (and all ChannelML file values) in SI Units so need to convert v first...
    
    v = v * 0.001   ? temporarily set v to units of equation...
            
    alpha = 2500/(1 + ( (1.5e-3 *(exp (-85*v))) / ca_conc))
        
    ? Set correct units of alpha for NEURON
    alpha = alpha * 0.001 
    
    v = v * 1000   ? reset v
        
     
    ? Found a generic form of the rate equation for beta, using expression: 1500/(1 + (ca_conc / (1.5e-4 * (exp (-77*v)))))
    
    ? Note: Equation (and all ChannelML file values) in SI Units so need to convert v first...
    
    v = v * 0.001   ? temporarily set v to units of equation...
            
    beta = 1500/(1 + (ca_conc / (1.5e-4 * (exp (-77*v)))))
        
    ? Set correct units of beta for NEURON
    beta = beta * 0.001 
    
    v = v * 1000   ? reset v
        
    mtau = 1/(temp_adj_m*(alpha + beta))
    minf = alpha/(alpha + beta)
    


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

    
            
                
           

        
    ?      ***  Adding rate equations for gate: n  ***
         
    ? Found a generic form of the rate equation for tau, using expression: 0.005
    
    ? Note: Equation (and all ChannelML file values) in SI Units so need to convert v first...
    
    v = v * 0.001   ? temporarily set v to units of equation...
            
    tau = 0.005
        
    ? Set correct units of tau for NEURON
    tau = tau * 1000 
    
    v = v * 1000   ? reset v
        
    ntau = tau/temp_adj_n
     
    ? Found a generic form of the rate equation for inf, using expression: 1
    
    ? Note: Equation (and all ChannelML file values) in SI Units so need to convert v first...
    
    v = v * 0.001   ? temporarily set v to units of equation...
            
    inf = 1
         
    
    v = v * 1000   ? reset v
        
    ninf = inf
    


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

         

}


UNITSON



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