Calcium response prediction in the striatal spines depending on input timing (Nakano et al. 2013)

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Accession:151458
We construct an electric compartment model of the striatal medium spiny neuron with a realistic morphology and predict the calcium responses in the synaptic spines with variable timings of the glutamatergic and dopaminergic inputs and the postsynaptic action potentials. The model was validated by reproducing the responses to current inputs and could predict the electric and calcium responses to glutamatergic inputs and back-propagating action potential in the proximal and distal synaptic spines during up and down states.
Reference:
1 . Nakano T, Yoshimoto J, Doya K (2013) A model-based prediction of the calcium responses in the striatal synaptic spines depending on the timing of cortical and dopaminergic inputs and post-synaptic spikes. Front Comput Neurosci 7:119 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I A; I K; I K,leak; I K,Ca; I CAN; I Sodium; I Calcium; I Potassium; I A, slow; I Krp; I R; I Q; I Na, leak; I Ca,p; Ca pump;
Gap Junctions:
Receptor(s): D1; AMPA; NMDA; Glutamate; Dopaminergic Receptor; IP3;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Reinforcement Learning; STDP; Calcium dynamics; Reward-modulated STDP;
Implementer(s): Nakano, Takashi [nakano.takashi at gmail.com];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; D1; AMPA; NMDA; Glutamate; Dopaminergic Receptor; IP3; I Na,p; I Na,t; I L high threshold; I A; I K; I K,leak; I K,Ca; I CAN; I Sodium; I Calcium; I Potassium; I A, slow; I Krp; I R; I Q; I Na, leak; I Ca,p; Ca pump;
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Nakano_FICN_model
stim_files2
tau_tables
readme.html
AMPA.mod
bkkca.mod *
cadyn.mod
caL.mod
caL13.mod
caldyn.mod
can.mod
caq.mod
car.mod *
cat.mod
damsg.mod
ER.mod
GABA.mod *
kaf.mod *
kas.mod *
kir.mod
krp.mod *
MGLU.mod
naf.mod
nap.mod *
NMDA.mod
skkca.mod *
stim.mod *
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_IVsaveplot.hoc
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_plot_pre_spine.hoc
_reset.hoc
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_saveplots.hoc
_timed_input_1AP_spine_post.hoc
_timed_input_Glu.hoc
all_tau_vecs.hoc *
baseline_values.txt
basic_procs.hoc
create_mspcells.hoc *
current_clamp.ses
fig4a.png
make_netstims.hoc
mosinit.hoc
msp_template.hoc
nacb_main.hoc
netstims_template.hoc *
posttiming.txt
set_synapse.hoc
set_synapse_caL.hoc
set_synapse_caL13.hoc
set_synapse_can.hoc
set_synapse_caq.hoc
set_synapse_ER.hoc
set_synapse_kir.hoc
set_synapse_naf.hoc
set_synapse_NMDA.hoc
stimxout_jns_sqwave_noinput.dat
synapse_templates.hoc
                            
TITLE N-type calcium channel for nucleus accumbens neuron 
: comments at end of file

UNITS {
	(mV) = (millivolt)
	(mA) = (milliamp)
	(S) = (siemens)
	(molar) = (1/liter)
	(mM) = (millimolar)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

NEURON {
	SUFFIX can
	USEION ca READ cai, cao WRITE ica
	RANGE pbar, ica
		POINTER mu
}

PARAMETER {
	pbar = 1.0e-5	(cm/s)		: vh = -100 mV, 120 ms pulse to 0 mV

	mvhalf = -8.7	(mV)		: Churchill 1998, fig 5
	mslope = -7.4	(mV)		: Churchill 1998, fig 5
	mshift = 0	(mV)

	hvhalf = -74.8	(mV)		: McNaughton 1997, Table 1
	hslope = 6.5	(mV)		: McNaughton 1997, Table 1
	hshift = 0	(mV)
	htau = 70.0	(ms)		: McNaughton 1997, Table 2 (tau1 in Ca)

	vm = -17.19  	(mV)		: fit from Kasai 1992, fig 15
	k = 15.22   	(mV)		: fit from Kasai 1992, fig 15
	kpr = 23.82   	(mV)		: fit from Kasai 1992, fig 15
	c = 0.03856   	(/ms-mV)	: fit from Kasai 1992, fig 15
	cpr = 0.3842	(/ms)		: fit from Kasai 1992, fig 15

	a = 0.21		: percent inactivation
	qfact = 3		: both m & h recorded at 22 C
}

ASSIGNED { 
    v		(mV)
    ica 	(mA/cm2)

    celsius	(degC)
    cai		(mM)
    cao		(mM)
    
    minf
    mtau	(ms)

    hinf

		mu (1)
}

STATE {
    m h
}

BREAKPOINT {
    SOLVE states METHOD cnexp
    ica  = ghk(v,cai,cao) * pbar * m * m * (a*h + (1-a))*(1-(mu-1)*0.8)    : Kasai 92, Brown 93
}

INITIAL {
    settables(v)
    m = minf
    h = hinf
}

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

PROCEDURE settables( v (mV) ) {
	LOCAL malpha, mbeta
	
	TABLE minf, hinf, mtau DEPEND mshift, hshift
        FROM -100 TO 100 WITH 201

		minf = 1  /  ( 1 + exp( (v-mvhalf-mshift) / mslope) )
		hinf = 1  /  ( 1 + exp( (v-hvhalf-hshift) / hslope) )

		malpha = c * (v-vm) / ( exp((v-vm)/k) - 1 )
		mbeta = cpr * exp(v/kpr)		: Kasai 1992, fig 15
		mtau = 1 / (malpha + mbeta)
}


::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::

: ghk() borrowed from cachan.mod share file in Neuron
FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) {
	LOCAL z, eci, eco
	z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
	eco = co*efun(z)
	eci = ci*efun(-z)
	:high cao charge moves inward
	:negative potential charge moves inward
	ghk = (.001)*2*FARADAY*(eci - eco)
}

FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}


COMMENT
Brown AM, Schwindt PC, Crill WE (1993) Voltage dependence and activation
kinetics of pharmacologically defined components of the high-threshold
calcium current in rat neocortical neurons. J Neurophysiol 70:1530-1543.

Churchill D, Macvicar BA (1998) Biophysical and pharmacological
characterization of voltage-dependent Ca2+ channels in neurons isolated
from rat nucleus accumbens. J Neurophysiol 79:635-647.

Kasai H, Neher E (1992) Dihydropyridine-sensitive and
omega-conotoxin-sensitive calcium channels in a mammalian
neuroblastoma-glioma cell line. J Physiol 448:161-188.

Koch, C., and Segev, I., eds. (1998). Methods in Neuronal Modeling: From
Ions to Networks, 2 edn (Cambridge, MA, MIT Press).

Hille, B. (1992). Ionic Channels of Excitable Membranes, 2 edn
(Sunderland, MA, Sinauer Associates Inc.).

McNaughton NCL, Randall AD (1997) Electrophysiological properties of the
human N-type calcium Ca2+ channel: I. Channel Gating in Ca2+, Ba2+, and
Sr2+ containing solutions. Neuropharm 36:895-915.



This is the w-conotoxin GV1A sensitive current in fig 5 from Churchill.


The standard HH model uses a linear approximation to the driving force
for an ion: (Vm - ez).  This is ok for na and k, but not ca - calcium
rectifies at high potentials because 
	1. internal and external concentrations of ca are so different,
	making outward current flow much more difficult than inward 
	2. calcium is divalent so rectification is more sudden than for na
	and k. (Hille 1992, pg 107)

Accordingly, we need to replace the HH formulation with the GHK model,
which accounts for this phenomenon.  The GHK equation is eq 6.6 in Koch
1998, pg 217 - it expresses Ica in terms of Ca channel permeability
(Perm,ca) times a mess. The mess can be circumvented using the ghk
function below, which is included in the Neuron share files.  Perm,ca
can be expressed in an HH-like fashion as 
	Perm,ca = pcabar * mca * mca 	(or however many m's and h's)
where pcabar has dimensions of permeability but can be thought of as max
conductance (Koch says it should be about 10^7 times smaller than the HH
gbar - dont know) and mca is analagous to m (check out Koch 1998 pg 144)

Calcium current can then be modeled as 
	ica = pcabar * mca * mca * ghk()

Jason Moyer 2004 - jtmoyer@seas.upenn.edu

ENDCOMMENT



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