AP initiation, propagation, and cortical invasion in a Layer 5 pyramidal cell (Anderson et 2018)

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" ... High frequency (~130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. ...We found robust AP propagation throughout the complex axonal arbor of the hyperdirect neuron. Even at therapeutic DBS frequencies, stimulation induced APs could reach all of the intracortical axon terminals with ~100% fidelity. The functional result of this high frequency axonal driving of the thousands of synaptic connections made by each directly stimulated hyperdirect neuron is a profound synaptic suppression that would effectively disconnect the neuron from the cortical circuitry. ..."
1 . Anderson RW, Farokhniaee A, Gunalan K, Howell B, McIntyre CC (2018) Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation Brain Stimulation
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon;
Brain Region(s)/Organism:
Cell Type(s): Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell;
Gap Junctions:
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Parkinson's; Deep brain stimulation;
Search NeuronDB for information about:  Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell;
// --------------------------------------------------------------
// passive & active membrane 
// --------------------------------------------------------------

proc init_shu_axon() {

//global variable made specific to shu
cm_myelin_shu = 0.04
g_pas_node_shu = 0.02
gna_node_shu = 7500
gkv_axon_shu = 1000
gna_dend_shu = 20

forsec wholeaxon {
  // na+ channels
  insert naShu

  ra = 100
  Ra = ra
  //global_ra = ra

  insert pas
  rm = 40000
  cm = 0.7

  g_pas = 1/rm
  e_pas = v_init

  Ek = -90
  Ena = 60


//not using myelinated axon yet, uncomment once we have it.
  // exceptions along the axon
  forsec myelinseclist cm = cm_myelin_shu*1
  forsec myelinseclist g_pas = 0.00002
  forsec nodeseclist g_pas = g_pas_node_shu

  forsec myelinseclist gbar_naShu = gna_dend_shu*1
  forsec nodeseclist gbar_naShu = gna_node_shu/5

// na channels
  forsec binzeggerCorticofugal gbar_naShu = gna_node_shu/3
  forsec firstOrder gbar_naShu = gna_node_shu/8.333
  forsec secondOrder gbar_naShu = gna_node_shu/10
  forsec thirdOrder gbar_naShu = gna_node_shu/20
//  forsec "node" gbar_kvShu = gkv_axon_shu  
// this is added by Yu at Oct.13

  // kv delayed rectifier channels
  forsec binzeggerCorticofugal { insert kvShu  gbar_kvShu = gkv_axon_shu/2 }
  forsec firstOrder { insert kvShu  gbar_kvShu = gkv_axon_shu/5 }
  forsec secondOrder { insert kvShu  gbar_kvShu = gkv_axon_shu/10 }
  forsec thirdOrder { insert kvShu  gbar_kvShu = gkv_axon_shu/20 }

  forsec wholeaxon if(ismembrane("k_ion")) ek = Ek
  forsec wholeaxon if(ismembrane("na_ion")) {
    ena = Ena
    // seems to be necessary for 3d cells to shift Na kinetics -5 mV
    vshift_naShu = -5



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