Nigral dopaminergic neurons: effects of ethanol on Ih (Migliore et al. 2008)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:112359
We use a realistic computational model of dopaminergic neurons in vivo to suggest that ethanol, through its effects on Ih, modifies the temporal structure of the spiking activity. The model predicts that the dopamine level may increase much more during bursting than pacemaking activity, especially in those brain regions with a slow dopamine clearance rate. The results suggest that a selective pharmacological remedy could thus be devised against the rewarding effects of ethanol that are postulated to mediate alcohol abuse and addiction, targeting the specific HCN genes expressed in dopaminergic neurons.
Reference:
1 . Migliore M, Cannia C, Canavier CC (2008) A modeling study suggesting a possible pharmacological target to mitigate the effects of ethanol on reward-related dopaminergic signaling. J Neurophysiol 99:2703-7 [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; Electrogenic pump;
Brain Region(s)/Organism:
Cell Type(s): Substantia nigra pars compacta DA cell;
Channel(s): I Na,t; I A; I K; I K,leak; I h; I Calcium; Na/K pump;
Gap Junctions:
Receptor(s): AMPA; NMDA; Glutamate; Gaba;
Gene(s):
Transmitter(s): Dopamine;
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Bursting; Active Dendrites; Detailed Neuronal Models; Action Potentials; Pathophysiology; Sodium pump; Alcohol Use Disorder;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Substantia nigra pars compacta DA cell; AMPA; NMDA; Glutamate; Gaba; I Na,t; I A; I K; I K,leak; I h; I Calcium; Na/K pump; Dopamine;
/
modeldb-etoh
readme.html
ampasyn.mod *
cabalan.mod *
cachan.mod
capump.mod *
dop.mod *
hh3.mod *
IhDA.mod
kca.mod *
leak.mod *
nabalan.mod *
nmdasyn.mod *
pump.mod *
damodel3.ses
fig3.hoc
mosinit.hoc
screenshot.jpg
x1e0p9927-b.dat
x2e0p9927-b.dat
                            
TITLE Calcium dependent potassium channel (small conductance SK)
 

UNITS {
        (molar) = (1/liter)
        (pA) =  (picoamp)
	(mV) =	(millivolt)
        (S)  =  (siemens)
	(mA) =	(milliamp)
	(mM) =	(millimolar)
}


INDEPENDENT {v FROM -100 TO 50 WITH 50 (mV)}

NEURON {
	SUFFIX kca
	USEION ca READ cai
	USEION k WRITE ik
	RANGE  gkbar,km,oinf,n
 
}


PARAMETER {
        dt  (ms)
        cai (mM)
        celsius = 35   (degC)
        gkbar = 800e-6 (S/cm2)
        ek = -100      (mV)
        km = 0.00019   (mM)
        n  = 4.0       (1)
        
        
}

ASSIGNED { 
           ik		(mA/cm2)
           oinf           
}


BREAKPOINT {
        oinf = 1/(1 + pow(km/cai,n))
	ik = oinf*gkbar*(v - ek)
}