Active dendrites shape signaling microdomains in hippocampal neurons (Basak & Narayanan 2018)

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Accession:244848
The spatiotemporal spread of biochemical signals in neurons and other cells regulate signaling specificity, tuning of signal propagation, along with specificity and clustering of adaptive plasticity. Theoretical and experimental studies have demonstrated a critical role for cellular morphology and the topology of signaling networks in regulating this spread. In this study, we add a significantly complex dimension to this narrative by demonstrating that voltage-gated ion channels (A-type Potassium channels and T-type Calcium channels) on the plasma membrane could actively amplify or suppress the strength and spread of downstream signaling components. We employed a multiscale, multicompartmental, morphologically realistic, conductance-based model that accounted for the biophysics of electrical signaling and the biochemistry of calcium handling and downstream enzymatic signaling in a hippocampal pyramidal neuron. We chose the calcium – calmodulin – calcium/calmodulin-dependent protein kinase II (CaMKII) – protein phosphatase 1 (PP1) signaling pathway owing to its critical importance to several forms of neuronal plasticity, and employed physiologically relevant theta-burst stimulation (TBS) or theta-burst pairing (TBP) protocol to initiate a calcium microdomain through NMDAR activation at a synapse.
Reference:
1 . Basak R, Narayanan R (2018) Active dendrites regulate the spatiotemporal spread of signaling microdomains. PLoS Comput Biol 14:e1006485 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite; Synapse; Channel/Receptor; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): Ca pump; I A; I_SERCA; I Calcium; I_K,Na; I h; I Potassium;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Calcium dynamics; Reaction-diffusion; Signaling pathways; Synaptic Plasticity;
Implementer(s): Basak, Reshma [reshmab at iisc.ac.in]; Narayanan, Rishikesh [rishi at iisc.ac.in];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; NMDA; I A; I h; I Calcium; I Potassium; I_SERCA; I_K,Na; Ca pump;
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Basak_Narayayanan_2018
Spine1000_sample
readme.txt
apamp.mod
caminmax.mod
car.mod
cat.mod
ghkampa.mod
ghknmda.mod
h.mod
kadist.mod *
kaprox.mod
kdrca1.mod *
modcamechs.mod
na3.mod
nax.mod
vmax.mod
distance.hoc
distance_SD.hoc
Fig_13.hoc
mosinit.hoc
n123.hoc *
ObliquePath.hoc *
oblique-paths.hoc *
Sample_output_Calcium.txt
                            
// This template creates the Basal Path lists, starting from the
// section attached to the trunk and ending with the basal tip section 
// written by Terrence Brannon, modified by Yiota Poirazi, July 2001, poirazi@LNC.usc.edu

begintemplate ObliquePath

public dtrunk_to_tip, trunk_section, root_oblique

strdef sexec

objref trunk_section
strdef trunk_section_name

objref root_oblique
strdef root_oblique_name

objref tip_section
strdef tip_section_name

objref oblique_path

proc init () {
  sec_count=0

  forsec $o1 {

    if (sec_count==1) {
       root_oblique    = new SectionRef()
       root_oblique_name=secname()
    }
      
    if (!sec_count) {
       distance(0,1)
       trunk_section  = new SectionRef()
       trunk_section_name=secname()
      }
    sec_count=sec_count+1

    tip_section    = new SectionRef()
    tip_section_name=secname()
  }

  access root_oblique.sec
  distance(0,0)
  access tip_section.sec
  dtrunk_to_tip=distance(1,1)

//  printf("ObliquePath trunk_section: %s root_oblique: %s tip_section: %s distance between root_oblique and tip_section: %g\n", trunk_section_name, root_oblique_name, tip_section_name, dtrunk_to_tip)
}

endtemplate ObliquePath

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