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
                            
// fig2A_c91662.hoc
// modified from fig2A.hoc from Migliore et al 2005 oblique model
// http://senselab.med.yale.edu/modeldb/showmodel.asp?model=55035
// to replace original model's default cell with c91662

{load_file("nrngui.hoc")}
// {cvode_active(1)} // uncomment for cvode however cvode incompat. for calcium analysis

numaxon=1
numsoma=1
numbasal=52
numapical=70
numtrunk=49

// xopen("geo5038804.hoc")             // geometry file for default cell
{xopen("c91662.ses")}  // a cell thats shape is similar to the one in Chen C et al. 2005
{load_file("obliques_primary_tuft.hoc")} // defines SectionLists
{xopen("fixnseg.hoc")}

// Omori et al. 2009 define a step function for Rm that is a high resistance, RmDend near
// the soma and then 350 +- 100 microns from the soma drops to 1/10 that value, RmDistalDend
Rm = 10^4.5 // 31622  lower limit from Omori et al. 2009, Michele's original value: 28000  // ohm cm2
RmDend = Rm
RmDistalDend = 10^3.5 // 3162.2 upper limit from Omori et al. 2009.
// Rm for Omori et al. 2006 value ~900 ohm cm2 (some value less than 1000)
// note also that pressing the leaky dendrites button now makes the model like Omori et
// al. 2009's paper range limits for Rm in a step distribution.
RmSoma = Rm
RmAx = Rm
{load_file("leaky_distal.hoc")} // procedures make_leaky_distal_Rm(), make_const_dend_Rm()
Cm    = 1
CmSoma= Cm
CmAx  = Cm
CmDend = Cm

RaAll= 150
RaSoma=150  
RaAx = 50

Vrest = -65
// now handled in paper....hoc: dt = 0.025 // dt =0.1 is OK for demo
gna =  .025
AXONM = 5
gkdr = 0.01
celsius = 35.0  
KMULT =  0.03 // Michele suggests that changing these to 0.04 from 0.03
KMULTP = 0.03 // is within the physiological range
ghd=0.00005

// the below 2 get reset later but must be defined to show up in gui text editors
gc=0  // used for setting the T, L, and N Ca2+ currents max conductance
gKc=0 // used for setting the Ca2+ sensitive K current max conductance
gt=0  // used for setting the T-type Ca current max cond. to a particular value

alzheimers_flag=0 // flag turns true when simulating alzheimers
current_marker_color=3 // starts out blue (3), red is 2
apic_resize_factor=1 // default value doesn't change anything, 10, 1/10 typical choices
apic_comp_index=0 // selects in text box which compartment is specifically changed, 0-128 valid choices
marker_graph=1 // 1 for marker graphs
line_graph=1 // 1 for line graphs
strdef current_marker_style
current_marker_style="O"
current_marker_size=3
current_cai_marker=3 // peak internal Ca2+ concentration graphs:  3=triangle 2=square
current_cai_marker_color=1 // 1=black, 2=red
aBeta_concentration_factor=1 // this is used to model smaller concentrations of aBeta
			     // than were measured experimentally.  The assumption is
// that the blocking due to a smaller value of aBeta would be linearly proportional to
// the full blocking as a factor of the ratio of the model concentration divided by the
// experimentally measured concentration (1 uM aBeta).
scale_ka=1 // used to scale the A-type current gmax's in the Migliore distribution
scale_obliques=1 // used to scale the A-type current gmax's on the relative distrib. in the obliq.s
objref g, b1, b2, c, d, stim, distrx, distry, distrt, cdistry
objref peak_ca_graph, peak_optical_graph

objref distrca, distr_cai_t // store the maximum cai values and times those max's occurred
objref tmp_vecx, tmp_vecy
objref b3
objref obliquex, obliquey, primaryx, primaryy, tuftx, tufty
objref obliqueca, primaryca, tuftca
objref obliqueoptical, primaryoptical, tuftoptical
objref p, chen_c_bpAP_peaks
objref soma_v_vec, dend_v_vec
objref obdend_v_vec, healthy_obdend_v_vec, abeta_obdend_v_vec

forsec "axon" {insert pas e_pas=Vrest g_pas = 1/RmAx Ra=RaAx cm=CmAx}
forsec "soma" {insert pas e_pas=Vrest g_pas = 1/RmSoma Ra=RaSoma cm=CmSoma}

// the union of dendrites in dendrite and user5 in the original model are
// analagous to the union of the dendrites in basal and apic in c91662

// forsec "dendrite" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "basal" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
// forsec "user5" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "apic" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}

access soma

freq=50
geom_nseg()
// chance here to change the nseg for compartments if want to study effect of that
// high resolution for middle oblique of interest:


// for apicindex=73,79 {
//  apic[apicindex] nseg*=27

//forall { nseg*=27 }
/**/

tot=0
forall {tot=tot+nseg}
distance()  // establishes soma (still accessed) as origin for distance(x) function

tstop=20

load_file("control_boxes.hoc")

p = new PlotShape()
p.exec_menu("Shape Plot")
p.size(-194.658,304.758,-223.667,609.667)
p.variable("v")
p.show(0)

rel=0.5
soma {
  stim= new IClamp(rel)
  stim.amp=0 // was 2.5 in original Migliore et al. 2005 model
  stim.dur=1.5
  stim.del=1
}
axon {
  stim= new IClamp(1)
  stim.amp=.1  // just a short small pulse is all that is neces. in axon to start bAP
  stim.dur=.2
  stim.del=0  // start stimulus right away since takes a little while to prop. to soma
}
axon { pt3dchange(0,1) } // change the diameter to 1 um prox to soma to match impedance for bAP

{load_file("distribute_currents.hoc")}
{load_file("init_and_run_and_graph.hoc")}
{load_file("aBeta.hoc")} // aBeta.hoc must be loaded after the cell is created
{load_file("shrink_obliques.hoc")} // electrically remove obliques
{load_file("oblique_scaled_ka.hoc")}
store_healthy_g_A() // store A current conductances for healthy cell.

// compare between healthy and aBeta applied cells backpropagating action potentials
objref healthy_bpAPs, aBeta_bpAPs
// note that the above stored peak voltages are aligned with the distrx vectors which
// contain the distance from the soma to the apical dendrite
objref percent_increase, experiment_indicies, per_inc_between_240_300, x_between_240_300
// experiment_indicies hold the indicies of distr(x or y) that correspond to the range
// that Chen C measured increases in bpAPs
objref g1

{load_file("figs.hoc")}  // contains procedures to create figures for Dend. Hypoth. paper

scale_ka=1  // throughout the whole cell
scale_obliques=3 // use 3 times ka slope in the obliques in standard model for this study
assign_relative_ka()

store_healthy_g_A()  // reassign this distribution as the healthy (control) one.

load_file("generate_conc_graph.hoc") // contains procs for concentration dependence study
load_file("oblique_application.hoc") // graphs comparison between oblique aBeta and control
load_file("bAP_peak_vecs.hoc")