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

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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]
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;
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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
                            
COMMENT by Johannes Luthman:

    This mechanism is based on DCNsyn.mod in this project. What's added here is
    paired-pulse depression of the synapse's current, based on Shin et al, 2007
    (PLOSone issue 5, e485, page 2), on which the changes in terminology
    compared to DCNsyn.mod are based.
    The depression is implemented via the change from [g = B - A] in DCNsyn.mod
    to [g = (B - A) * deprLevel] here, and the calculation of deprLevel on each
    input (NETRECEIVE).

ENDCOMMENT

NEURON {
	POINT_PROCESS DCNsynGABA
	NONSPECIFIC_CURRENT i
	RANGE g, i, e, tauRise, tauFall, startDeprLevel, deprLevel
}

UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
}

PARAMETER {
	tauRise = 1 (ms)
	tauFall = 1 (ms)
	e = 0 (mV)
	startDeprLevel = 1 : set this in hoc to the depression level reached at 
	        : steady state (use the equation for relProbSS, below) by the 
	        : used GABAergic input frequency.
}

ASSIGNED {
    relProbSS (1) : This corresponds to Rss in the article (given in COMMENT at top).
    relProb[2] (1) : This corresponds to Rn and Rn-1 in the article.
    freq (1/s) : This corresponds to r in the article.
    tau (ms)
    tSpikes[2] (ms)
    ISI (ms)
    deprLevel (1) : level of synaptic depression. The conductance is
                  : multiplied by this factor in BREAKPOINT.
    notFirstSpike (1) : boolean used to set up values of previous step on first
                      : call to this mechanism.

	v (mV)
	i (nA)
	g (microsiemens)
	factor
}

STATE {
	A (microsiemens)
	B (microsiemens)
}

INITIAL {
	LOCAL tp
	if (tauRise/tauFall > .9999) {
		tauRise = .9999*tauFall
	}
	A = 0
	B = 0
	tp = (tauRise*tauFall)/(tauFall - tauRise) * log(tauFall/tauRise)
	factor = -exp(-tp/tauRise) + exp(-tp/tauFall)
	factor = 1/factor

    notFirstSpike = 0
}

BREAKPOINT {
    : Here the conductance is updated each time step, while the NET_RECEIVE block
    : is only invoked by being contacted by a NetCon object.
  	SOLVE state METHOD cnexp
   	g = (B - A) * deprLevel
   	i = g*(v - e)   	
}

DERIVATIVE state {
	A' = -A/tauRise
	B' = -B/tauFall
}

NET_RECEIVE(weight (microsiemens)) {
    deprLevel = giveFractionG()
    state_discontinuity(A, A + weight*factor)
	state_discontinuity(B, B + weight*factor)
}

FUNCTION giveFractionG() {
	if (notFirstSpike) {
        : Set the current spike to the present time, and calculate ISI as the
        : difference in time from the last pass through here.
        tSpikes[0] = tSpikes[1]
        tSpikes[1] = t
        ISI = tSpikes[1] - tSpikes[0]
        freq = 1000 / ISI
        
        relProbSS = 0.08 + 0.60*exp(-2.84*freq) + 0.32*exp(-0.02*freq)
        tau = 2 + 2500*exp(-0.274*freq) + 100*exp(-0.022*freq)
        relProb[1] = relProb[0] + (relProbSS - relProb[0]) * (1-exp(-ISI/tau))
        relProb[0] = relProb[1]

        giveFractionG = relProb[1]
	} else {
	    tSpikes[1] = t
	    relProb[0] = startDeprLevel
	    notFirstSpike = 1
	    giveFractionG = relProb[0]
	}
}

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