KV1 channel governs cerebellar output to thalamus (Ovsepian et al. 2013)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:150024
The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 alpha andKV beta2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. ... Through the use of multi-compartmental modelling and ... the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established.
Reference:
1 . Ovsepian SV, Steuber V, Le Berre M, O'Hara L, O'Leary VB, Dolly JO (2013) A defined heteromeric KV1 channel stabilizes the intrinsic pacemaking and regulates the output of deep cerebellar nuclear neurons to thalamic targets. J Physiol 591:1771-91 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Cerebellum deep nucleus neuron;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I K; I h; I CAN; I_Ks;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s): Kv1.1 KCNA1; Kv1.2 KCNA2;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Bursting; Ion Channel Kinetics; Active Dendrites; Detailed Neuronal Models; Intrinsic plasticity; Rebound firing;
Implementer(s): Steuber, Volker [v.steuber at herts.ac.uk]; Luthman, Johannes [jwluthman at gmail.com];
Search NeuronDB for information about:  AMPA; NMDA; I Na,p; I Na,t; I L high threshold; I T low threshold; I K; I h; I CAN; I_Ks;
/
CNModel_May2013
readme.txt
CaConc.mod *
CaHVA.mod *
CalConc.mod *
CaLVA.mod *
DCNsyn.mod *
DCNsynGABA.mod *
DCNsynNMDA.mod *
fKdr.mod *
GammaStim.mod *
h.mod *
Ifluct8.mod *
NaF.mod *
NaP.mod *
pasDCN.mod *
SK.mod *
sKdr.mod *
TNC.mod *
DCN_cip_axis_main.hoc
DCN_cip_fi_main.hoc
DCN_mechs1.hoc *
DCN_mechs2.hoc
DCN_morph.hoc *
DCN_params.hoc
DCN_params_axis.hoc
DCN_params_fi_init.hoc
DCN_params_rebound.hoc
DCN_rebound_main.hoc
DCN_recording.hoc
DCN_spontact_loop_main.hoc
                            
TITLE High voltage activated calcium current (CaHVA) of deep cerebellar nucleus (DCN) neuron
COMMENT
    Translated from GENESIS by Johannes Luthman and Volker Steuber. 
    This mechanism and the other calcium channel (CaLVA.mod) are the only channel
    mechanisms of the DCN model that use the GHK mechanism to calculate reversal
    potential. Thus, extracellular Ca concentration is of importance and shall be 
    set from hoc.

    Calcium entering the neuron through this channel is kept track of by CaConc.mod
    and affects the conductance of the SK.mod channel mechanism.
ENDCOMMENT 

NEURON { 
	SUFFIX CaHVA 
	USEION ca READ cai, cao WRITE ica
	RANGE perm, ica, m, cai
	GLOBAL qdeltat
} 
 
UNITS { 
	(mA) = (milliamp) 
	(mV) = (millivolt) 
	(molar) = (1/liter)
	(mM) = (millimolar)
} 
 
PARAMETER { 
    qdeltat = 1
    perm = 7.5e-6 (cm/seconds)
} 

ASSIGNED {
	v (mV)
    cai (mM)
    cao (mM)     
	ica (mA/cm2) 
	minf (1)
	taum (ms) 
	celsius (degC)
	T (kelvin)
    A (1)
} 

STATE {
	m
} 

INITIAL { 
    T = 273.15 + celsius
    rate(v)
    m = minf 
} 
 
BREAKPOINT { 
    SOLVE states METHOD cnexp 
    A = getGHKexp(v)
    : "4.47814e6 * v / T" in the following is the simplification of the GHK
    : current equation's (z^2 * F^2 * (0.001) * v) / (R * T). [*(0.001) is to get 
    : volt from NEURON's mV.] Together with the simplification in getGHKexp() 
    : (below), this speeds up the whole DCN simulation (without synapses) by 8%.
    : The division of the calcium concentrations (mM) by 1000 gives molar as 
    : required by the GHK current equation.
    ica = perm * m*m*m * (4.47814e6 * v / T) * ((cai/1000) - (cao/1000) * A) / (1 - A)
} 
 
DERIVATIVE states { 
	rate(v) 
	m' = (minf - m)/taum 
} 

PROCEDURE rate(v(mV)) {
	TABLE minf, taum FROM -150 TO 100 WITH 300
    minf = 1 / (1 + exp((v + 34.5) / -9))
    taum = 1 / ((31.746 * ((exp((v - 5) / -13.89) + 1) ^ -1)) + (3.97e-4 * (v + 8.9)) * ((exp((v + 8.9) / 5) - 1) ^ -1))
    taum = taum / qdeltat
} 

FUNCTION getGHKexp(v(mV)) {
    TABLE DEPEND T FROM -150 TO 100 WITH 300 
    getGHKexp = exp(-23.20764929 * v / T): =the calculated values of
            : getGHKexp = exp((-z * F * (0.001) * v) / (R * T)).
}