A detailed Purkinje cell model (Masoli et al 2015)

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Accession:229585
The Purkinje cell is one of the most complex type of neuron in the central nervous system and is well known for its massive dendritic tree. The initiation of the action potential was theorized to be due to the high calcium channels presence in the dendritic tree but, in the last years, this idea was revised. In fact, the Axon Initial Segment, the first section of the axon was seen to be critical for the spontaneous generation of action potentials. The model reproduces the behaviours linked to the presence of this fundamental sections and the interplay with the other parts of the neuron.
Reference:
1 . Masoli S, Solinas S, D'Angelo E (2015) Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization. Front Cell Neurosci 9:47 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon;
Brain Region(s)/Organism: Cerebellum;
Cell Type(s): Cerebellum Purkinje GABA cell;
Channel(s): I Sodium; I Calcium; I Na,t; I K;
Gap Junctions:
Receptor(s):
Gene(s): Cav2.1 CACNA1A; Cav3.1 CACNA1G; Cav3.2 CACNA1H; Cav3.3 CACNA1I; Nav1.6 SCN8A; Kv1.1 KCNA1; Kv1.5 KCNA5; Kv3.3 KCNC3; Kv3.4 KCNC4; Kv4.3 KCND3; KCa1.1 KCNMA1; KCa2.2 KCNN2; KCa3.1 KCNN4; Kir2.1 KCNJ2; HCN1;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s): Bursting; Detailed Neuronal Models; Action Potentials; Action Potential Initiation; Axonal Action Potentials;
Implementer(s): Masoli, Stefano [stefano.masoli at unipv.it]; Solinas, Sergio [solinas at unipv.it];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,t; I K; I Sodium; I Calcium;
: Calcium ion accumulation with endogenous buffers, DCM and pump

COMMENT

The basic code of Example 9.8 and Example 9.9 from NEURON book was adapted as:

1) Extended using parameters from Schmidt et al. 2003.
2) Pump rate was tuned according to data from Maeda et al. 1999
3) DCM was introduced and tuned to approximate the effect of radial diffusion

Reference: Anwar H, Hong S, De Schutter E (2010) Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cell. Cerebellum*

*Article available as Open Access

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20981513

Written by Haroon Anwar, Computational Neuroscience Unit, Okinawa Institute of Science and Technology, 2010.
Contact: Haroon Anwar (anwar@oist.jp)

ENDCOMMENT


NEURON {
  SUFFIX cdp5
  USEION ca READ cao, cai, ica WRITE cai
  RANGE ica_pmp
  RANGE Nannuli, Buffnull2, rf3, rf4, vrat
  RANGE TotalPump

}


UNITS {
	(mol)   = (1)
	(molar) = (1/liter)
	(mM)    = (millimolar)
	(um)    = (micron)
	(mA)    = (milliamp)
	FARADAY = (faraday)  (10000 coulomb)
	PI      = (pi)       (1)
}

PARAMETER {
	Nannuli = 10.9495 (1)
	celsius (degC)
        
	cainull = 45e-6 (mM)
        mginull =.59    (mM)

:	values for a buffer compensating the diffusion

	Buffnull1 = 0	(mM)
	rf1 = 0.0134329	(/ms mM)
	rf2 = 0.0397469	(/ms)

	Buffnull2 = 60.9091	(mM)
	rf3 = 0.1435	(/ms mM)
	rf4 = 0.0014	(/ms)

:	values for benzothiazole coumarin (BTC)
	BTCnull = 0	(mM)
	b1 = 5.33	(/ms mM)
	b2 = 0.08	(/ms)

:	values for caged compound DMNPE-4
	DMNPEnull = 0	(mM)
	c1 = 5.63	(/ms mM)
	c2 = 0.107e-3	(/ms)

:       values for Calbindin (2 high and 2 low affinity binding sites)

        CBnull=	.16             (mM)
        nf1   =43.5           (/ms mM)
        nf2   =3.58e-2        (/ms)
        ns1   =5.5            (/ms mM)
        ns2   =0.26e-2        (/ms)

:       values for Parvalbumin

        PVnull  = .08           (mM)
        m1    = 1.07e2        (/ms mM)
        m2    = 9.5e-4                (/ms)
        p1    = 0.8           (/ms mM)
        p2    = 2.5e-2                (/ms)

  	kpmp1    = 3e-3       (/mM-ms)
  	kpmp2    = 1.75e-5   (/ms)
  	kpmp3    = 7.255e-5  (/ms)
	TotalPump = 1e-9	(mol/cm2)	

}

ASSIGNED {
	diam      (um)
	ica       (mA/cm2)
	ica_pmp   (mA/cm2)
	parea     (um)     : pump area per unit length
	parea2	  (um)
	cai       (mM)
	mgi	(mM)
	vrat	(1)	
}

CONSTANT { cao = 2	(mM) }

STATE {
	: ca[0] is equivalent to cai
	: ca[] are very small, so specify absolute tolerance
	: let it be ~1.5 - 2 orders of magnitude smaller than baseline level

	ca		(mM)    <1e-3>
	mg		(mM)	<1e-6>
	
	Buff1		(mM)	
	Buff1_ca	(mM)

	Buff2		(mM)
	Buff2_ca	(mM)

	BTC		(mM)
	BTC_ca		(mM)

	DMNPE		(mM)
	DMNPE_ca	(mM)	

        CB		(mM)
        CB_f_ca		(mM)
        CB_ca_s		(mM)
        CB_ca_ca	(mM)

        PV		(mM)
        PV_ca		(mM)
        PV_mg		(mM)
	
	pump		(mol/cm2) <1e-15>
	pumpca		(mol/cm2) <1e-15>

}

BREAKPOINT {
	SOLVE state METHOD sparse
}

LOCAL factors_done

INITIAL {
		factors()

		ca = cainull
		mg = mginull
		
		Buff1 = ssBuff1()
		Buff1_ca = ssBuff1ca()

		Buff2 = ssBuff2()
		Buff2_ca = ssBuff2ca()

		BTC = ssBTC()
		BTC_ca = ssBTCca()		

		DMNPE = ssDMNPE()
		DMNPE_ca = ssDMNPEca()

		CB = ssCB( kdf(), kds())   
	        CB_f_ca = ssCBfast( kdf(), kds())
       	 	CB_ca_s = ssCBslow( kdf(), kds())
        	CB_ca_ca = ssCBca( kdf(), kds())

        	PV = ssPV( kdc(), kdm())
        	PV_ca = ssPVca(kdc(), kdm())
        	PV_mg = ssPVmg(kdc(), kdm())

		
  	parea = PI*diam
	parea2 = PI*(diam-0.2)
	ica = 0
	ica_pmp = 0
:	ica_pmp_last = 0
	pump = TotalPump
	pumpca = 0
	
	cai = ca
}

PROCEDURE factors() {
        LOCAL r, dr2
        r = 1/2                : starts at edge (half diam)
        dr2 = r/(Nannuli-1)/2  : full thickness of outermost annulus,
        vrat = PI*(r-dr2/2)*2*dr2  : interior half
        r = r - dr2
}


LOCAL dsq, dsqvol  : can't define local variable in KINETIC block
                   :   or use in COMPARTMENT statement

KINETIC state {
  COMPARTMENT diam*diam*vrat {ca mg Buff1 Buff1_ca Buff2 Buff2_ca BTC BTC_ca DMNPE DMNPE_ca CB CB_f_ca CB_ca_s CB_ca_ca PV PV_ca PV_mg}
  COMPARTMENT (1e10)*parea {pump pumpca}


	:pump
	~ ca + pump <-> pumpca  (kpmp1*parea*(1e10), kpmp2*parea*(1e10))
	~ pumpca <-> pump   (kpmp3*parea*(1e10), 0)
  	CONSERVE pump + pumpca = TotalPump * parea * (1e10)
	
	ica_pmp = 2*FARADAY*(f_flux - b_flux)/parea	
	: all currents except pump
	: ica is Ca efflux
	~ ca << (-ica*PI*diam/(2*FARADAY))

	:RADIAL DIFFUSION OF ca, mg and mobile buffers

	dsq = diam*diam
		dsqvol = dsq*vrat
		~ ca + Buff1 <-> Buff1_ca (rf1*dsqvol, rf2*dsqvol)
		~ ca + Buff2 <-> Buff2_ca (rf3*dsqvol, rf4*dsqvol)
		~ ca + BTC <-> BTC_ca (b1*dsqvol, b2*dsqvol)
		~ ca + DMNPE <-> DMNPE_ca (c1*dsqvol, c2*dsqvol)
		:Calbindin	
		~ ca + CB <-> CB_ca_s (nf1*dsqvol, nf2*dsqvol)
	       	~ ca + CB <-> CB_f_ca (ns1*dsqvol, ns2*dsqvol)
        	~ ca + CB_f_ca <-> CB_ca_ca (nf1*dsqvol, nf2*dsqvol)
        	~ ca + CB_ca_s <-> CB_ca_ca (ns1*dsqvol, ns2*dsqvol)

		:Paravalbumin
        	~ ca + PV <-> PV_ca (m1*dsqvol, m2*dsqvol)
        	~ mg + PV <-> PV_mg (p1*dsqvol, p2*dsqvol)


  	cai = ca
	mgi = mg
}

FUNCTION ssBuff1() (mM) {
	ssBuff1 = Buffnull1/(1+((rf1/rf2)*cainull))
}
FUNCTION ssBuff1ca() (mM) {
	ssBuff1ca = Buffnull1/(1+(rf2/(rf1*cainull)))
}
FUNCTION ssBuff2() (mM) {
        ssBuff2 = Buffnull2/(1+((rf3/rf4)*cainull))
}
FUNCTION ssBuff2ca() (mM) {
        ssBuff2ca = Buffnull2/(1+(rf4/(rf3*cainull)))
}

FUNCTION ssBTC() (mM) {
	ssBTC = BTCnull/(1+((b1/b2)*cainull))
}

FUNCTION ssBTCca() (mM) {
	ssBTCca = BTCnull/(1+(b2/(b1*cainull)))
}

FUNCTION ssDMNPE() (mM) {
	ssDMNPE = DMNPEnull/(1+((c1/c2)*cainull))
}

FUNCTION ssDMNPEca() (mM) {
	ssDMNPEca = DMNPEnull/(1+(c2/(c1*cainull)))
}

FUNCTION ssCB( kdf(), kds()) (mM) {
	ssCB = CBnull/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBfast( kdf(), kds()) (mM) {
	ssCBfast = (CBnull*kds())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBslow( kdf(), kds()) (mM) {
	ssCBslow = (CBnull*kdf())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBca(kdf(), kds()) (mM) {
	ssCBca = (CBnull*kdf()*kds())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION kdf() (1) {
	kdf = (cainull*nf1)/nf2
}
FUNCTION kds() (1) {
	kds = (cainull*ns1)/ns2
}
FUNCTION kdc() (1) {
	kdc = (cainull*m1)/m2
}
FUNCTION kdm() (1) {
	kdm = (mginull*p1)/p2
}
FUNCTION ssPV( kdc(), kdm()) (mM) {
	ssPV = PVnull/(1+kdc()+kdm())
}
FUNCTION ssPVca( kdc(), kdm()) (mM) {
	ssPVca = (PVnull*kdc())/(1+kdc()+kdm())
}
FUNCTION ssPVmg( kdc(), kdm()) (mM) {
	ssPVmg = (PVnull*kdm())/(1+kdc()+kdm())
}

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