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]
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 GLU 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 GLU 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
                            
// distribute_currents.hoc

plateau_500=0 // switch determines if to assign IA mx cond. values at 
// greater than 500 um from the soma to a value which is equal to that at 500 um
// in the below function

proc assign_migliore_distribution() { // this new version scales kab, kad throughout the cell
  print "Assigning Migliore distribution of currents with new I_A slope scale ",scale_ka
  forsec "axon" {   
                insert nax gbar_nax=gna * AXONM
                insert kdr gkdrbar_kdr=gkdr
//              insert kap gkabar_kap = KMULTP // J. Neurosci., September 8, 2004 • 24(36):7903–7915
//                                                Rhodes et al.  seems to indicate no IA in axons
}

  forsec "soma" {  
		insert ds // measure max v, [Ca2+]internal, and times these occur
		insert hd ghdbar_hd=ghd	vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
//		print "adding additional currents KM and Na,p to soma"
//		insert KM
//		gMbar_KM=0.002
//		insert nap
//		gbar_nap=0.001
  }
  // scale_ka=1 // factor for scaling ka default set in fig2A_c91662.hoc
  forsec "basal" {
		insert hd ghdbar_hd=ghd vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0
 		for (x) if (x>0 && x<1) { xdist = distance(x)
                  ghdbar_hd(x) = ghd*(1+3*xdist/100)
                  if (xdist > 100){
                    if ((xdist > 500)&&(plateau_500)) {
		      vhalfl_hd=-81
                      gkabar_kad(x) = KMULT*(1+scale_ka*500/100)
                    } else { // 100<x<500
		      vhalfl_hd=-81
                      gkabar_kad(x) = KMULT*(1+scale_ka*xdist/100)
                    }
                  } else { // x<100
		      vhalfl_hd=-73
                      gkabar_kap(x) = KMULTP*(1+scale_ka*xdist/100)
                  }
                }
  }                
  // forsec "apical_dendrite" {
  forsec "apic" { // includes primary dend., obliques, and tuft
	insert ds
	insert hd ghdbar_hd=ghd
        insert na3 gbar_na3=gna
        insert kdr gkdrbar_kdr=gkdr
	insert kap gkabar_kap=0
	insert kad gkabar_kad=0

	for (x) if (x>0 && x<1) { xdist = distance(x)
                  ghdbar_hd(x) = ghd*(1+3*xdist/100)
                  if (xdist > 100){
                    if ((xdist > 500)&&(plateau_500)) {
		      vhalfl_hd=-81
                      gkabar_kad(x) = KMULT*(1+scale_ka*500/100)
                    } else { // 100<x<500
		      vhalfl_hd=-81
                      gkabar_kad(x) = KMULT*(1+scale_ka*xdist/100)
                    }
                  } else { // x<100
		      vhalfl_hd=-73
                      gkabar_kap(x) = KMULTP*(1+scale_ka*xdist/100)
                  }
        }
  }
}
proc assign_migliore_distribution_old() { // this first method used the absolute value at the tip of the 
// distal dendrite to assign (a possibly scaled) distribution of kad
  print "Assigning Migliore distribution of currents with I_A scale ",scale_ka
  forsec "axon" {   
                insert nax gbar_nax=gna * AXONM
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
  }

  forsec "soma" {  
		insert ds // measure max voltages, max [Ca2+]internal, and times they occur
		insert hd ghdbar_hd=ghd	vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
  }
  // scale_ka=1 // factor for scaling ka default set in fig2A_c91662.hoc
  forsec "basal" {
		insert hd ghdbar_hd=ghd vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0
		for (x) if (x>0 && x<1) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
					vhalfl_hd=-81
                        		gkabar_kad(x) = KMULT*(1+scale_ka*xdist/100)
                			} else {
					vhalfl_hd=-73
                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
               				}
		}
  }
                
  // forsec "apical_dendrite" {
  forsec "apic" {
		insert ds // measure max voltages, max [Ca2+]internal, and their times
		insert hd ghdbar_hd=ghd
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0

		for (x) if (x>0 && x<1) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
					vhalfl_hd=-81
                        		gkabar_kad(x) = KMULT*(1+scale_ka*xdist/100)
                			} else {
					vhalfl_hd=-73
                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
               				}
		}
  }
}

assign_migliore_distribution()
load_file("add_ca.hoc")  // add L,N,T-type Ca2+ chan, pump, and Ca2+ sens. K+ current
init_ca() // initialize calcium channels max conductances
// for c91662 note that the apic subsection contains the analagous pieces of
// both apical_dendrite and user5 in the default cell from modeldb and that
// they are set with identical intrinsic currents and parameters
//forsec "user5" {
//	insert ds
//		insert hd ghdbar_hd=ghd
//              insert na3 gbar_na3=gna
//              insert kdr gkdrbar_kdr=gkdr
//		insert kap gkabar_kap=0
//		insert kad gkabar_kad=0

//		for (x) if (x>0 && x<1) { xdist = distance(x)
//                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
//                		if (xdist > 100){
//					vhalfl_hd=-81
//                        		gkabar_kad(x) = KMULT*(1+xdist/100)
//                			} else {
//					vhalfl_hd=-73
//                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
//               				}
//		}
//}

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