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]
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
                            
// init_and_run_and_graph.hoc
// model specific versions of initialization and run procedures including graphing after the run
reset_e_pas = -1
proc init() {
	t=0
        forall {
        v=Vrest
        if (ismembrane("nax") || ismembrane("na3")) {ena=55}
        if (ismembrane("kdr") || ismembrane("kap") || ismembrane("kad")) {ek=-90}
        if (ismembrane("hd") ) {ehd_hd=-30}
	}
	finitialize(Vrest) // use v_init if want to change.
        fcurrent()
	forall if (ismembrane("cacum")) {
	       for(x,0) irest_cacum(x)=ica(x)
// bug fix removes this	       for(x,0) irest_cacum(x)=-ica(x) // this init is not correct in the sense
// that it does not make the starting resting membrane potential an equilibrium point
// which is what it was intended to be.  Since the calcium currents are small here
// it is only a small pertubation (see the use of irest in cacumm.mod)
	}
  if (reset_e_pas) {
        forall {
	  for (x) {
           if (ismembrane("na3")||ismembrane("nax")){e_pas(x)=v(x)+(ina(x)+ik(x))/g_pas(x)}
	    if (ismembrane("hd")) {e_pas(x)=e_pas(x)+i_hd(x)/g_pas(x)}
	    if (ismembrane("ca_ion")) {e_pas(x)=e_pas(x)+ica(x)/g_pas(x)}
	  }
	}
  }
// uncomment for cvode however cvode incompat. with Calcium analysis code
//	cvode.re_init()
//	cvode.event(tstop)
	access soma
	g.begin()
	// init_ca()  // initialize Ca2+ channels and Ca2+ sens. K+ current
	// print "Ca2+ channels initialized"
	frecord_init() // properly resets vectors for recording
}


proc advance() {
	fadvance()
	g.plot(t)
	g.flush()
	p.flush()
	doNotify()
}
objref sect_list_2getparent
objref obdend_ca_vec  // record the Ca2+ in an oblique dendrite

proc runp() {
	// record soma and an apical dendrite's voltages in vectors
	soma_v_vec=new Vector()
	dend_v_vec=new Vector()
	obdend_v_vec=new Vector()
	soma_v_vec.record(&soma.v(0.5))
	dend_v_vec.record(&apic[16].v(0.5))  // 16 is 264.5, 14 is 233 um, 18 is 284 um from soma
	obdend_v_vec.record(&apic[76].v(0.5))  // tip of the middle oblique featured in fig 1

	obdend_ca_vec=new Vector()
	obdend_ca_vec.record(&apic[76].v(0.5))  // tip of the middle oblique featured in fig 1

        stdinit()
	continuerun(tstop)

	distrx=new Vector() // dist. from soma stored here used for several other vec's x coord's
	distry=new Vector()
//	obliquex=new Vector() // holds distance from soma to oblique dend
//	obliquey=new Vector() // holds max voltage corresponding to distance
	// in the primary apical dendrite (the trunk)
	primaryx=new Vector() // holds distance from soma to primary dend
	primaryy=new Vector() // holds max voltage corresponding to distance
	primaryca=new Vector() // holds max calcium corresponding to distance
	primaryoptical=new Vector() // holds max optical corresponding to distance
	// in the tuft
	tuftx=new Vector() // holds distance from soma to tuft dend
	tufty=new Vector() // holds max voltage corresponding to distance
	tuftca=new Vector() // holds max ca corresponding to distance
	tuftoptical=new Vector() // holds optical voltage corresponding to distance

	distrca=new Vector() // holds the maximum cai per compartment
	distr_cai_t=new Vector() // holds the time at which those max's occurred

//	forsec "apical_dendrite" {
	forsec "apic" {
		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			distrx.append(distance(x))       // note these vecs used only for markers so don't 
			distry.append(vmax_ds(x)-Vrest)  // need to be connected to previous dends like lines
			distrca.append(cmax_cacum(x))  // use absolute value to start with
			distr_cai_t.append(ca_tmax_cacum(x))
			}
		}
	}
// role taken over by bAP_peak_vecs.hoc
//	forsec obliques {
//		for (x) if (x>0 && x<1) {
//			if (diam>=0.) {
//			obliquex.append(distance(x)) 
//			obliquey.append(vmax_ds(x)-Vrest)
//			}
//		}
//	}
	forsec primary {
		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			primaryx.append(distance(x)) 
			primaryy.append(vmax_ds(x)-Vrest)
			primaryca.append(cmax_cacum(x))
			primaryoptical.append((cmax_cacum(x)-cai0_cacum(x))/cai0_cacum(x))
			}
		}
	}
	forsec tuft {
		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			tuftx.append(distance(x)) // used only for markers
			tufty.append(vmax_ds(x)-Vrest)
			tuftca.append(cmax_cacum(x))
			tuftoptical.append((cmax_cacum(x)-cai0_cacum(x))/cai0_cacum(x))
			}
		}
	}
	// also receive the time of the peak - used interactively (via gui) to study time delivery of peak bAP
	distrt=new Vector() // can be graphed with distrx as x coordinate
//	forsec "apical_dendrite" {
	forsec "apic" {
		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			distrt.append(tmax_ds(x))
			}
		}
	}
      assign_dist_peak_vecs()
      if (marker_graph) {
//         distry.mark(c,distrx,current_marker_style,current_marker_size,current_marker_color+alzheimers_flag,2)
//         obliquey.mark(d,obliquex,current_marker_style,current_marker_size+1,current_marker_color-alzheimers_flag,2)
         primaryy.mark(d,primaryx,"s",current_marker_size+1,7+alzheimers_flag,2)
         tufty.mark(d,tuftx,"t",current_marker_size+1,4+alzheimers_flag,2)
         primaryca.mark(peak_ca_graph,primaryx,"s",current_marker_size+1,7+alzheimers_flag,2)
         tuftca.mark(peak_ca_graph,tuftx,"t",current_marker_size+1,4+alzheimers_flag,2)
         primaryoptical.mark(peak_optical_graph,primaryx,"s",current_marker_size+1,7+alzheimers_flag,2)
         tuftoptical.mark(peak_optical_graph,tuftx,"t",current_marker_size+1,4+alzheimers_flag,2)
      }
      if (line_graph) {
         // if line graph then make line graphs for bAPs if abeta (alzheimers_flag) shift color
         // now done at bottom of this proc with calls to bAP_peak_vecs.hoc procs
//         forsec obliques {
//            color_choice=1+alzheimers_flag // black or red if abeta present
//            tmp_vecx=new Vector()
//            tmp_vecy=new Vector()
//		for (x) if (x>0 && x<1) {
//			if (diam>=0.) {
//			tmp_vecx.append(distance(x)) 
//			tmp_vecy.append(vmax_ds(x)-Vrest)
//			}
//		}
//            tmp_vecy.line(d,tmp_vecx, color_choice,1)
//         }
         // the primary is a special case where there are no branches and
         // only apic[25] has nseg different than 1
         tmp_vecx=new Vector()
         tmp_vecy=new Vector()
         forsec primary {
            color_choice=7+alzheimers_flag // purple or yellow if abeta present
		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			tmp_vecx.append(distance(x)) 
			tmp_vecy.append(vmax_ds(x)-Vrest)
			}
		}
         }
         tmp_vecy.line(d,tmp_vecx, color_choice,4)
         forsec tuft {
            color_choice=4+alzheimers_flag //  if abeta present
            tmp_vecx=new Vector()
            tmp_vecy=new Vector()
         // here need to add in code that will connect tuft dends to their parents
         // which are either the primary trunk or other tufts
            sect_list_2getparent = new SectionRef()
            sect_list_2getparent.parent {
                  x=0.5*((nseg-1)/nseg+1) // finds last relative (0-1) point on parent
              	tmp_vecx.append(distance(x)) // that we want to start with
			tmp_vecy.append(vmax_ds(x)-Vrest)
            }

		for (x) if (x>0 && x<1) {
			if (diam>=0.) {
			tmp_vecx.append(distance(x))
			tmp_vecy.append(vmax_ds(x)-Vrest)
			}
		}
            tmp_vecy.line(d,tmp_vecx, color_choice,1)
         }
      }
      // for model to Chen statistics comparison:
      chen_c_bpAP_peaks=new Vector() // apic[15] through 19 have middles

	// within Chen C 2005 range of 240-300 ums.  It was found by hand that these
	// compartments apic[15 through 19] correspond to the primary dendrite, the likely
	// source of Chen C's electrical recordings.
	/* oc>for i=14,19 {apic[i] print secname(),.5,distance(.5),v }
	apic[14]0.5 233.72056 -46.048939
	apic[15]0.5 253.83815 -41.003093
	apic[16]0.5 264.45777 -38.230327
	apic[17]0.5 276.62687 -34.690309
	apic[18]0.5 284.63212 -32.181721
	apic[19]0.5 295.92992 -28.539688
	oc>
	*/

	for i=15,19 {
		apic[i] chen_c_bpAP_peaks.append(vmax_ds(0.5)-Vrest)
	}
	soma chen_c_bpAP_soma_peak=vmax_ds(0.5)-Vrest
//	c.flush()
	doNotify()
//      assign_dist_peak_vecs() // new procs which connect the oblique dendrites
      print "calling graph_dist_peak_vecs()"
      graph_dist_peak_vecs()
}

proc runm() {
  print "model run"
  runp()  // used to be runp(1) however the argument is no longer used
}