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

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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.
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 cell;
Channel(s): Ca pump; I A; I_SERCA; I Calcium; I_K,Na; I h; I Potassium;
Gap Junctions:
Receptor(s): AMPA; NMDA;
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]; Narayanan, Rishikesh [rishi at];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; AMPA; NMDA; I A; I h; I Calcium; I Potassium; I_SERCA; I_K,Na; Ca pump;
kadist.mod *
kdrca1.mod *
n123.hoc *
ObliquePath.hoc *
oblique-paths.hoc *
The files in this directory incorporate calcium handling mechanisms involved in the Ca – Calmodulin – CaMKII – PP1 pathway in a conductance-based neuronal CA1 pyramidal model developed in Rathour and Narayanan, PNAS, 2014. The simulation environment is NEURON.  The model contains Na, KDR, KA, h, CaT and CaR currents, and employs GHK-based implementations of AMPA and NMDA receptors. Fig13.hoc helps recreate Fig 13 of the following paper:

Basak R, Narayanan R. Active dendrites regulate the spatiotemporal spread of signaling microdomains; Plos Comp Biol (in Press).

Running Fig13.hoc will create files that will contain .txt files storing the values of various species (Ca, Calmodulin, phosphorylated CaMKII etc.) as they evolve with time at various spatial locations, specifically the 100 µm length around the spine-containing synapse in the oblique containing the calcium handling mechanisms. The default number of spines in the oblique in the .hoc file is 1000. Example output was obtained by running the defaultgrad_Dependent() function. This shows the example data generated for the Calcium species for 100 ms of simulation time at the central location of the oblique and is provided in the Sample_output_Calcium.txt file in this directory. The calcium handling mechanisms were incorporated in the file modcamechs.mod, which is modified from Ashhad and Narayanan; Journal of physiology; 2013

Implemented by Reshma Basak and Rishikesh Narayanan. Contact reshmab at .

If you need more help running this model please see:

20181008 A correction from Reshma Basak for a shell volume scaling bug
in modcamechs.mod and an updated sample calcium .txt file. The bug
resulted in quantitative but not qualitative changes.

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