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 [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:
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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readme.html
cacumm.mod
cagk.mod *
cal2.mod *
can2.mod *
cat.mod *
distr.mod *
h.mod
ipulse2.mod *
kadist.mod
kaprox.mod
kdrca1.mod
na3n.mod
naxn.mod *
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
fig1.jpg
fig2.jpg
fig2A_c91662.hoc
fig3.jpg
fig3.ses
fig4.jpg
fig4.ses
fig5.jpg
fig6b.jpg
figs.hoc
find_averages.hoc
fixnseg.hoc
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
paper_fig_buttons.hoc
sectiontest.hoc
shrink_obliques.hoc
SubBranch.hoc
trigger_and_start.hoc
wait_for_go.hoc
                            
// add_ca.hoc
// add Ca2+ channels and pump from Michele's 2008 CA3 model 101629
// to the cell to model how Ca2+ increases with greater bAPs
// The T, N, and L-type Ca channels are included and also the
// Ca2+ sensitive K channel to balance the Ca2+ excitation
// Future modifications could be done using the distributions cited by
// Oh MM, et al. 2010 (Disterhoft lab review article):
// "...Studies have shown that VGCCs are non-uniformly distributed on CA1
// pyramidal cells: L and N-type VGCCs are found predominantly on the
// soma and proximal dendrites; T and R-type VGCCs are found
// predominantly on the apical dendrites (Westenbroek et al., 1990;
// Westenbroek et al., 1992; Christie et al., 1995; Magee et al., 1995;
// Magee and Johnston, 1995a, b; Westenbroek et al., 1995; Christie et
// al., 1996; Magee and Carruth, 1999).

gc=1.e-5 * 2.5 // 2.5x original 2008 Miglioire model distribution is new default
gKc=5e-5
gcal=gc*4
gcan=gc*4
gcat=gc

forsec "apic" { 
        insert cacum
        for (x, 0) depth_cacum(x)=diam(x)/2 // Ca2+ accumulation and pump 
	// see comment at top of this script:
        insert cal // L-type
	insert can // N-type
        insert cat // T-type Ca2+ channels
	insert cagk // Ca2+ sensitive K channel
}

// assume basal distribution of Ca channels similar to apical although
// there are no citations for this
forsec "basal" { 
    insert cacum
    for (x, 0) depth_cacum(x)=diam(x)/2 // Ca2+ accumulation and pump 
    insert cal // L-type
    insert can // N-type
    insert cat // T-type Ca2+ channels
    insert cagk // Ca2+ sensitive K channel

}

forsec "soma" { 
	insert cacum depth_cacum=diam/2
        insert cal 
        insert can 
        insert cat // according to Oh et al. (above quote) not present
	insert cagk  
}

proc init_ca() { // initializes calcium channels max conductances
     forall {
	    if (ismembrane("cal")) {
	       gcalbar_cal=gc*4
	       gbar_cagk= gKc 
	   }
	    if (ismembrane("can")) {
	       gcanbar_can=gc*4
	       gbar_cagk= gKc 
	   }
	   if (ismembrane("cat")) {
	       gcatbar_cat=gc
	       gbar_cagk= gKc 
	   }
     }
}

proc reset_ca() {
     gc=$1
     init_ca()
}

proc init_cat() { // pass this function the new value for cat everywhere
     forall {
	    if (ismembrane("cat")) {
	       gcatbar_cat=$1
	   }
     }

}