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

 Download zip file   Auto-launch 
Help downloading and running models
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;
/
CA1_abeta
translate
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
                            
TITLE K-A channel from Klee Ficker and Heinemann
: modified to account for Dax A Current ----------
: M.Migliore Jun 1997

UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
}

PARAMETER {
	celsius
        v (mV)
        gkabar=.008 (mho/cm2)
        vhalfn=-1   (mV)
        vhalfl=-56   (mV)
        a0l=0.05      (/ms)
        a0n=.1    (/ms)
        zetan=-1.8    (1)
        zetal=3    (1)
        gmn=0.39   (1)
        gml=1   (1)
        lmin=2  (mS)
        nmin=0.2  (mS)
        pw=-1    (1)
        tq=-40
        qq=5
        q10=5
        qtl=1
	ek
}


NEURON {
        SUFFIX kad
        USEION k READ ek WRITE ik
        RANGE gkabar,gka
        GLOBAL ninf,linf,taul,taun,lmin
}

STATE {
	n
        l
}

ASSIGNED {
	ik (mA/cm2)
        ninf
        linf      
        taul
        taun
        gka
}

INITIAL {
	rates(v)
	n=ninf
	l=linf
}

BREAKPOINT {
        SOLVE states METHOD cnexp
        gka = gkabar*n*l
        ik = gka*(v-ek)
}

FUNCTION alpn(v(mV)) {
LOCAL zeta
  zeta=zetan+pw/(1+exp((v-tq)/qq))
  alpn = exp(1.e-3*zeta*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betn(v(mV)) {
LOCAL zeta
  zeta=zetan+pw/(1+exp((v-tq)/qq))
  betn = exp(1.e-3*zeta*gmn*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION alpl(v(mV)) {
  alpl = exp(1.e-3*zetal*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betl(v(mV)) {
  betl = exp(1.e-3*zetal*gml*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
}

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        n' = (ninf - n)/taun
        l' =  (linf - l)/taul
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a,qt
        qt=q10^((celsius-24)/10)
        a = alpn(v)
        ninf = 1/(1 + a)
        taun = betn(v)/(qt*a0n*(1+a))
	if (taun<nmin) {taun=nmin}
        a = alpl(v)
        linf = 1/(1+ a)
	taul = 0.26*(v+50)/qtl
	if (taul<lmin/qtl) {taul=lmin/qtl}
}