Coincident glutamatergic depolarization effects on Cl- dynamics (Lombardi et al, 2021)

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Accession:266823
"... we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval..."
Reference:
1 . Lombardi A, Jedlicka P, Luhmann HJ, Kilb W (2021) Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons PLOS Comp Bio
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Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Dendrite;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA3 pyramidal GLU cell;
Channel(s):
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Short-term Synaptic Plasticity; Synaptic Plasticity; Chloride regulation;
Implementer(s): Jedlicka, Peter [jedlicka at em.uni-frankfurt.de]; Kilb, Werner [wkilb at uni-mainz.de];
Search NeuronDB for information about:  Hippocampus CA3 pyramidal GLU cell; GabaA; AMPA; NMDA; Gaba; Glutamate;
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_For Zip -Neuron-Models_AMPA-GABA
Fig6de_Ball-stick_tonic_GABA
cldif_CA3_NKCC1_HCO3.mod *
gabaA_Cl_HCO3.mod *
tonic.mod *
vecevent.mod *
cell_soma_dendrite_pas.hoc *
cell_soma_dendrite_tonicGABA.hoc
Determine_Rinput.ses
Determine_Rinput-Info.txt
Display_One_AMPA.ses
GABA-AMPA_BS-Effect-AMPA-on-tonic-GABA_Var-Cl_tauAMPA-hand.hoc
GABA-AMPA_BS-NOtonicGABA_Dif-gAMPA_Var-Cl.hoc
GABA-AMPA_BS-tonicGABA_Dif-gAMPA_Var-Cl.hoc
GABA-AMPA_BS-tonicGABA_One_AMPA.hoc
GABA-AMPA_BS-tonicGABA_var-temp_rel_AMPA_Var-Cl_tauGABA-hand_AMPA-hand.hoc
init_Cldif.hoc *
Isolated_Dendrite.ses *
start_GABA-AMPA_BS-NOtonicGABA_Dif-gAMPA_Var-Cl.hoc
start_GABA-AMPA_BS-passive_No-synGABA_var-temp_rel_AMPA_Var-Cl_AMPA-hand.hoc
start_GABA-AMPA_BS-tonicGABA_Dif-gAMPA_Var-Cl.hoc
start_GABA-AMPA_BS-tonicGABA_No-synGABA_var-temp_rel_AMPA_Var-Cl_AMPA-hand.hoc
start_GABA-AMPA_BS-tonicGABA_One_AMPA.hoc
start_GABA-AMPA_BS-tonicGABA_var-temp_rel_AMPA_Var-Cl_tauGABA-hand_AMPA-hand.hoc
                            
// Simulation and analysis of Spatiotemporal Component of Cl- Gradients in a isolated dendrite
// Here simulation of one AMPA Synapses
// Here application in a simple Ball and Stick Model


// Determination Parameters AMPA
  ANZAHL_AMPA = 1           //Anzahl der synaptischen Pulse
  G_AMPA = 0.000305 * 0   //Value from Lombardi et al 2018 
  E_AMPA = 0                // Reversal Potential of Exp2Syn
  DECAY_AMPA = 11      
  AMPA_SYN_LOCATION = 0.5   // Position GABA Synapse for Pulses
  AMPA_Delay = 198000


// Determine [Cl-]i -----------

   Cl_intra = 5              // mM

//----- Define run parameters ---------------------
  tstop = 200000   // Duration
  slowdown_start = AMPA_Delay - 1000
  v_init = -60   // Initial voltage
  dt_fast = 10      // Step Interval in ms
  dt_slow = 0.2      // Step Interval in ms

// Functions init_changedt and set_changedt -----------------//
//                                                           //
// Event Handler that decreases dt at a given timepoint      //
// required for fast equilibratin at low temp resolution     //
// but a high resolution for phases with synaptic events      //
// ----------------------------------------------------------//

objref fih
fih = new FInitializeHandler("init_slowchangedt()")

proc init_slowchangedt() {
  printf("\n Init_slowchangedt-ok, Start = %g ms \n",slowdown_start)
  dt = dt_fast  
  cvode.event(slowdown_start, "set_slowdt()")
}

proc set_slowdt() {
  printf("\n Call executed - changed to slow dt \n")
  dt = dt_slow
  if (cvode.active()) {
    cvode.re_init()
  } else {
    fcurrent()
  }
}


//-- Initialize Graph for Display of [Cli]i in the right scale
objectvar Cl_graph
Cl_graph = new Graph(0)
Cl_graph.size(slowdown_start,tstop,5.76,5.77)
Cl_graph.view(slowdown_start, 5.76, tstop - slowdown_start, 0.01, 462, 636, 961.2, 200.8)
graphList[0].append(Cl_graph)
Cl_graph.addexpr("dend.cli( 0.5 )", 1, 1, 0.8, 0.9, 2)

//----- Insert synapses -------------------------

  objref ampasyn
  dend {
    // insert AMPA synapse 
    ampasyn = new Exp2Syn(AMPA_SYN_LOCATION)
    ampasyn.tau1 = 0.1 
    ampasyn.tau2 = DECAY_AMPA
    ampasyn.e = E_AMPA
  }

// Definition of synaptic Stimuli
  objref stimAMPApuls      //Pulssequenz AMPA
  stimAMPApuls = new NetStim(AMPA_SYN_LOCATION)
  stimAMPApuls.number = ANZAHL_AMPA


// Linkage of synaptic Inputs
  objref synpulseampa

// Update Cl- homeostasis in all compartments ----------------------------------------------
  forsec all {
    cli0_cldif_CA3_NKCC1_HCO3 = Cl_intra
    cli_Start_cldif_CA3_NKCC1_HCO3 = Cl_intra
    cli_cldif_CA3_NKCC1_HCO3 = Cl_intra
  }

//-- Stimulate AMPA --------------------------------------------------------------
   dend {
      stimAMPApuls.start = AMPA_Delay 
      synpulseampa = new NetCon(stimAMPApuls, ampasyn, 0, 0, G_AMPA)
   }

// Run Simulation --------------------------------------------------------
   run()