NAcc medium spiny neuron: effects of cannabinoid withdrawal (Spiga et al. 2010)

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Accession:126640
Cannabinoid withdrawal produces a hypofunction of dopaminergic neurons targeting medium spiny neurons (MSN) of the forebrain. Administration of a CB1 receptor antagonist to control rats provoked structural abnormalities, reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis. Experimental observations were incorporated into a realistic computational model which predicts a strong reduction in the excitability of morphologically-altered MSN, yielding a significant reduction in action potential output. These paper provided direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their post synaptic counterpart, supporting a hypodopaminergic state as a distinctive feature of the “addicted brain”.
Reference:
1 . Spiga S, Lintas A, Migliore M, Diana M (2010) Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependence. Addict Biol 15:266-76 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism: Basal ganglia;
Cell Type(s): Nucleus accumbens spiny projection neuron;
Channel(s): I Na,t; I A; I Potassium; I A, slow; I Krp;
Gap Junctions:
Receptor(s): AMPA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Activity Patterns; Active Dendrites; Detailed Neuronal Models; Action Potentials; Synaptic Integration; Addiction;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  AMPA; I Na,t; I A; I Potassium; I A, slow; I Krp; Glutamate;
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withdrawal
tau_tables
readme.html
kaf.mod *
kas.mod *
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naf.mod *
netstimd.mod
after.ses
after-withdrawal.hoc
all_tau_vecs.hoc
control.hoc
control.ses
fixnseg.hoc *
mosinit.hoc
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soma17.hoc
                            
TITLE Krp (4ap resistant, persistent) current for nucleus accumbens

COMMENT

Nisenbaum ES, Wilson CJ, Foehring RC, Surmeier DJ (1996). Isolation and
characterization of a persistent potassium current in neostriatal neurons. J
Neurophys 76(2): 1180-1194.

Recorded at 22C - corrected to 35C with qfact 3

Jason Moyer 2004 - jtmoyer@seas.upenn.edu

ENDCOMMENT

UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
        (S)  = (siemens)
}
 
NEURON {
        SUFFIX krp
        USEION k READ ek WRITE ik
        RANGE  gkbar, ik
}
 
PARAMETER {
	gkbar   =   0.002 (S/cm2)

	mvhalf = -13.5		(mV)	: Nisenbaum 1996, Fig 6C
	mslope = -11.8		(mV)	: Nisenbaum 1996, Fig 6C
	mshift = 0		(mV)

	hvhalf = -54.7		(mV)	: Nisenbaum 1996, Fig 9D
	hslope = 18.6		(mV)	: Nisenbaum 1996, Fig 9D
 	hshift = 0		(mV)

 	a = 0.7				: matched to Nisenbaum 1996, figure 9A (with qfact = 1)
 	qfact = 3.0
}
 
STATE { m h }
 
ASSIGNED {
	ek				(mV)
        v 				(mV)
        ik 				(mA/cm2)
        gk				(S/cm2)
        minf 
	hinf
    }
 
BREAKPOINT {
        SOLVE state METHOD cnexp
        gk = gkbar * m * (a*h + (1-a)) 
        ik = gk * ( v - ek )
}
 

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

FUNCTION_TABLE taumkrp (v(mV))  (ms)
FUNCTION_TABLE tauhkrp (v(mV))  (ms)

DERIVATIVE state { 
        rates(v)
        m' = (minf - m) / (taumkrp(v)/qfact)
        h' = (hinf - h) / (tauhkrp(v)/qfact)
}
 
PROCEDURE rates(v (mV)) {  
	TABLE minf, hinf DEPEND mshift, hshift
		FROM -200 TO 200 WITH 201
			minf = 1 / (1 + exp( (v - mvhalf - mshift) / mslope ))
			hinf = 1 / (1 + exp( (v - hvhalf - hshift) / hslope ))
}
 
 

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