Alcohol action in a detailed Purkinje neuron model and an efficient simplified model (Forrest 2015)

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Accession:180789
" ... we employ a novel reduction algorithm to produce a 2 compartment model of the cerebellar Purkinje neuron from a previously published, 1089 compartment model. It runs more than 400 times faster and retains the electrical behavior of the full model. So, it is more suitable for inclusion in large network models, where computational power is a limiting issue. We show the utility of this reduced model by demonstrating that it can replicate the full model’s response to alcohol, which can in turn reproduce experimental recordings from Purkinje neurons following alcohol application. ..."
Reference:
1 . Forrest MD (2015) Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster. BMC Neurosci 16:27 [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;
Brain Region(s)/Organism: Cerebellum;
Cell Type(s): Cerebellum Purkinje GABA cell;
Channel(s): I Na,t; I T low threshold; I A; I K; I K,leak; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; I_HERG; Na/Ca exchanger; Na/K pump; I_AHP; I Cl, leak; I Na, leak; I Ca,p; I_KD; Ca pump;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Dendritic Action Potentials; Bursting; Ion Channel Kinetics; Oscillations; Simplified Models; Active Dendrites; Influence of Dendritic Geometry; Detailed Neuronal Models; Sodium pump; Depolarization block; Dendritic Bistability; Markov-type model; Alcohol Use Disorder;
Implementer(s): Forrest, Michael [mikeforrest at hotmail.com];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,t; I T low threshold; I A; I K; I K,leak; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; I_HERG; Na/Ca exchanger; Na/K pump; I_AHP; I Cl, leak; I Na, leak; I Ca,p; I_KD; Ca pump;
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Forrest2015
collapse_algorithm
README.txt
bkpkj.mod *
cad.mod *
cadiff.mod *
cae.mod *
cap2.mod *
captain.mod *
cat.mod *
cha.mod *
erg.mod *
gkca.mod *
hpkj.mod *
k23.mod *
ka.mod *
kc3.mod *
kd.mod *
kdyn.mod *
khh.mod *
km.mod *
kpkj.mod *
kpkj2.mod *
kpkjslow.mod *
kv1.mod *
leak.mod *
lkpkj.mod *
myexchanger.mod *
myexchangersoma.mod *
mypump.mod *
mypumpsoma.mod *
nadifl.mod *
narsg.mod *
newnew.mod *
pump.mod *
2_compartment.hoc
full.ses *
full_data_writer.hoc
full_morph.hoc
lesbos.ses *
mex.hoc
mosinit.hoc
mosinit_full.hoc
mosinit_simple.hoc
simple_data_writer.hoc
                            
: FORREST MD (2014) Two Compartment Model of the Cerebellar Purkinje Neuron

COMMENT

Ih current	 - hyperpolarization-activated nonspecific Na and K channel
		 - contributes to the resting membrane potential
		 - controls the afterhyperpolarization
Reference:

1.	Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current
	(Ih) and its contribution to pacemaker activity in rat CA1 hippocampal
	stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130,
	1996.

		V1/2 = -84.1 mV
		   k = 10.2
		reversal potential = -32.9 +/- 1.1 mV

at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s
at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms 
t2 = 1.04+/-0.16 s


2.	Maccaferri, G. et al. Properties of the
	Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal
	cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993.

		V1/2 = -97.9 mV
		   k = 13.4
		reversal potential = -18.3 mV

3.	Pape, H.C.  Queer current and pacemaker: The
	hyperpolarization-activated cation current in neurons, Annu. Rev. 
	Physiol. 58:299-327, 1996.

		single channel conductance is around 1 pS
		average channel density is below 0.5 um-2
		0.5 pS/um2 = 0.00005 mho/cm2 = 0.05 umho/cm2		
4.	Magee, J.C. Dendritic Hyperpolarization-Activated Currents Modify
	the Integrative Properties of Hippocampal CA1 Pyramidal Neurons, J.
	Neurosci., 18(19):7613-7624, 1998

Deals with Ih in CA1 pyramidal cells.  Finds that conductance density
increases with distance from the soma.

soma g = 0.0013846 mho/cm2
dendrite g (300-350 um away) = 0.0125 mho/cm2
see Table 1 in th paper

ENDCOMMENT

 UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
}
 
NEURON {
        SUFFIX cha
        USEION h READ eh WRITE ih VALENCE 1
        RANGE gkhbar,ih
        GLOBAL rinf, rexp, tau_r
}
 
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
 
PARAMETER {
        v (mV)
        p = 5 (degC)
        dt (ms)
        gkhbar = 0.001385       : 0.001385 (mho/cm2)			
        eh = -32.9 (mV)
}
 
STATE {
        r
}
 
ASSIGNED {
        ih (mA/cm2)
	rinf rexp
	tau_r
}
 
BREAKPOINT {
        SOLVE deriv METHOD derivimplicit
        ih = gkhbar*r*(v - eh)
}
 
INITIAL {
	rates(v)
	r = rinf
}

DERIVATIVE deriv { :Computes state variable h at current v and dt.
	rates(v)
	r' = (rinf - r)/tau_r
}

PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        TABLE rinf, rexp, tau_r DEPEND dt, p FROM -200
TO 100 WITH 300
	rinf = 1/(1 + exp((v+84.1)/10.2))
	rexp = 1 - exp(-dt/(tau_r))
	tau_r = 100 + 1/(exp(-17.9-0.116*v)+exp(-1.84+0.09*v))
}
 
UNITSON