Amyloid beta (IA block) effects on a model CA1 pyramidal cell (Morse et al. 2010)

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Accession:87284
The model simulations provide evidence oblique dendrites in CA1 pyramidal neurons are susceptible to hyper-excitability by amyloid beta block of the transient K+ channel, IA. See paper for details.
Reference:
1 . Morse TM, Carnevale NT, Mutalik PG, Migliore M, Shepherd GM (2010) Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study Front. Neural Circuits 4:16 [PubMed]
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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:
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I h; I K,Ca;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Dendritic Action Potentials; Active Dendrites; Detailed Neuronal Models; Pathophysiology; Aging/Alzheimer`s;
Implementer(s): Carnevale, Ted [Ted.Carnevale at Yale.edu]; Morse, Tom [Tom.Morse at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I h; I K,Ca;
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CA1_abeta
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cal2.mod *
can2.mod *
cat.mod *
distr.mod *
h.mod
ipulse2.mod *
kadist.mod
kaprox.mod
kdrca1.mod
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zcaquant.mod
aBeta.hoc
add_ca.hoc
bAP_peak_vecs.hoc
c91662.ses
C91662_Link.txt
cond_report.hoc
control_boxes.hoc
distribute_currents.hoc
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fig2A_c91662.hoc
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figs.hoc
find_averages.hoc
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GaspiriniEtAl2007Fig1Stimulation.ses
generate_conc_graph.hoc
gka_averager.hoc
graph_na3_kinetics.hoc
init_and_run_and_graph.hoc
leaky_distal.hoc
maxica.hoc
maxica.ses.20100525
mosinit.hoc
na3_shifter.hoc
ntc_additions.hoc
oblique_application.hoc
oblique_scaled_ka.hoc
obliques_primary_tuft.hoc
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sectiontest.hoc
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COMMENT
	calcium accumulation into a volume of area*depth next to the
	membrane with a decay (time constant tau) to resting level
	given by the global calcium variable cai0_ca_ion
	Modified to include a resting current (irest) and peak value
	(cmax)
	i is a dummy current needed to force a BREAKPOINT
	Note: irest cancels out resting calcium current contributions
	by mechanisms that write ica.  To initialize irest properly
	use a custom proc init that assigns values to irest as illustrated
	in this excerpt:
	finitialize(Vrest) // use v_init if want to change.
        fcurrent()
	forall if (ismembrane("cacum")) {
	       for(x,0) irest_cacum(x)=ica(x) // (fixed from =-ica minus sign bug)
	}

ENDCOMMENT

NEURON {
	SUFFIX cacum
	USEION ca READ ica WRITE cai
	NONSPECIFIC_CURRENT i
	RANGE depth, tau, cai0, cmax, irest, ca_tmax
}

UNITS {
        (um) = (micron)
	(mM) = (milli/liter)
	(mA) = (milliamp)
	F = (faraday) (coulombs)
}

PARAMETER {
	depth = 0.1 (um)	: assume volume = area*depth
	irest = 0  (mA/cm2)		: to be initialized in hoc	
	tau = 40 (ms) :  ~40 ms phenomenologically fits dendrite shafts, ~350 ms fits spines (murthy et al 2000 PNAS, earlier model default was 100 (ms)
	cai0 = 50e-6 (mM)	: Requires explicit use in INITIAL
			: block for it to take precedence over cai0_ca_ion
			: Do not forget to initialize in hoc if different
			: from this default.
}

ASSIGNED {
        ica      (mA/cm2)
        cmax     (milli/liter)
        ca_tmax  (ms)
        i        (mA/cm2)
}

STATE {
	cai (mM)
}

INITIAL {
	cai = cai0
:	irest = ica : this make simulations depend on end result of prior simulations
	cmax=cai
	ca_tmax=0
}

BREAKPOINT {
	SOLVE integrate METHOD derivimplicit
	if (cai>cmax) {cmax=cai ca_tmax=t}
	i=0
}

DERIVATIVE integrate {
	cai' = (irest-ica)/depth/F/2 * (1e4) + (cai0 - cai)/tau
}