Modelling reduced excitability in aged CA1 neurons as a Ca-dependent process (Markaki et al. 2005)

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"We use a multi-compartmental model of a CA1 pyramidal cell to study changes in hippocampal excitability that result from aging-induced alterations in calcium-dependent membrane mechanisms. The model incorporates N- and L-type calcium channels which are respectively coupled to fast and slow afterhyperpolarization potassium channels. Model parameters are calibrated using physiological data. Computer simulations reproduce the decreased excitability of aged CA1 cells, which results from increased internal calcium accumulation, subsequently larger postburst slow afterhyperpolarization, and enhanced spike frequency adaptation. We find that aging-induced alterations in CA1 excitability can be modelled with simple coupling mechanisms that selectively link specific types of calcium channels to specific calcium-dependent potassium channels."
1 . Markaki M, Orphanoudakis S, Poirazi P (2005) Modelling reduced excitability in aged CA1 neurons as a calcium-dependent process Neurocomputing 65-66:305-314
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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: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I N; I A; I K; I M; I K,Ca; I R;
Gap Junctions:
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Aging/Alzheimer`s;
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I N; I A; I K; I M; I K,Ca; I R;
basic_graphics.hoc *
basic-graphics.hoc *
choose-secs.hoc *
cut-sections.hoc *
deduce-ratio.hoc *
find-gmax.hoc *
GABA_shiftsyn.hoc *
GABA_shiftsyn_bg.hoc *
ken.h *
map-segments-to-3d.hoc *
maxmin.hoc *
mod_func.c *
newshiftsyn *
newshiftsyn.c *
num-rec.h *
salloc.hoc *
shiftsyn-init_bg.hoc *
shiftsyn-initA.hoc *
spikecount.hoc *
tune-epsps.hoc *
vector-distance.hoc *
verbose-system.hoc *
// This function is used to calculate the AMPA coductance values 
// such that a single pulse stimulus gives rise to a 5mV local depolarization 
// at every synapse location along the cell (each synapse has both an AMPA and an NMDA mechanism).
// AMPA values for each location tested, along the sections tested are saved in the tune_epsp_list
// written by Terrence Brannon, last modified by Yiota Poirazi, July 2001,

strdef fast_file
strdef sec_str, recstr, tuning_code
objref epsp_glu, epsp_nmda, vmvec, epsp_ic, tmpvec

proc tune_epsp_fast () { 
//  printf("proc tune_epsp_fast (%s.v(%g))\n", secname(), $2)

  R = $2                 //  synapse location
  epsp_glu  = new GLU(R)
  epsp_nmda = new NMDA(R)
  tuned = 0             //  initial values before tuning
  old_GMAX = 0
  while (!tuned) {

   epsp_glu.gmax  = GMAX     // previously calculated maximum AMPA conductance
   epsp_nmda.gmax = GMAX*NMDA_AMPA_RATIO  // maximum NMDA conductance 

   fakecell {                            // single shock current injection to a fake cell
     epsp_ic = new IClamp(0.5)           
     epsp_ic.amp = 1
     epsp_ic.dur = 1
     epsp_ic.del = 0.1*tstop

   setpointer epsp_glu.pre,  epsp_ic.i
   setpointer epsp_nmda.pre, epsp_ic.i

   tmpvec = new Vector(tstop/dt)
   sprint(recstr, "tmpvec.record(&%s.v(%g))", secname(), R) // record depolarization at synapse

   vmvec = tmpvec.c
   // test if resulting depolarization is closed to the desired value (5mV)

   if (epsilon_equal(vmvec.max(),desired_voltage,$3)) {
     tuned = 1  // if yes, stop         

   } else {     // if no, update the GMAX value and test again

     diffa = desired_voltage-BASELINE
     diffb = vmvec.max()-BASELINE
     ratio = diffa/diffb
     GMAX = GMAX*ratio

     print "\t\tnew GMAX: ", GMAX

 sprint(tuning_code,"%s tune_epsp_list.append(new EPSPTuning(\"%s\",%f,%f,1))", secname(), secname(), x, GMAX)
 $o4.printf("%s\n", tuning_code)


// test if difference between desired and actual voltage is smaller than epsilon

func epsilon_equal() {
  printf("epsilon_equal(%f,%f,%f)\n", $1,$2,$3)
  diff = ($1-$2)
  if (abs(diff) < $3) {
  } else {