CA1 pyramidal neuron: depolarization block (Bianchi et al. 2012)

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NEURON files from the paper: On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons by D.Bianchi, A. Marasco, A.Limongiello, C.Marchetti, H.Marie,B.Tirozzi, M.Migliore (2012). J Comput. Neurosci. In press. DOI: 10.1007/s10827-012-0383-y. Experimental findings shown that under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. We analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single-compartment. The results show the specic ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to depolarization block.
1 . Bianchi D, Marasco A, Limongiello A, Marchetti C, Marie H, Tirozzi B, Migliore M (2012) On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. J Comput Neurosci 33:207-25 [PubMed]
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,t; I A; I K; I M; I h; I K,Ca; I_AHP;
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Mathematica;
Model Concept(s): Simplified Models; Depolarization block; Bifurcation;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at-]; Limongiello, Alessandro [alessandro.limongiello at];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; GabaA; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I_AHP; Gaba; Glutamate;
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TITLE decay of internal calcium concentration
: Internal calcium concentration due to calcium currents and pump.
: Differential equations.
: Simple model of ATPase pump with 3 kinetic constants (Destexhe 92)
:     Cai + P <-> CaP -> Cao + P  (k1,k2,k3)
: A Michaelis-Menten approximation is assumed, which reduces the complexity
: of the system to 2 parameters: 
:       kt = <tot enzyme concentration> * k3  -> TIME CONSTANT OF THE PUMP
:	kd = k2/k1 (dissociation constant)    -> EQUILIBRIUM CALCIUM VALUE
: The values of these parameters are chosen assuming a high affinity of 
: the pump to calcium and a low transport capacity (cfr. Blaustein, 
: TINS, 11: 438, 1988, and references therein).  
: Units checked using "modlunit" -> factor 10000 needed in ca entry
: VERSION OF PUMP + DECAY (decay can be viewed as simplified buffering)
: All variables are range variables
: This mechanism was published in:  Destexhe, A. Babloyantz, A. and 
: Sejnowski, TJ.  Ionic mechanisms for intrinsic slow oscillations in
: thalamic relay neurons. Biophys. J. 65: 1538-1552, 1993)
: Written by Alain Destexhe, Salk Institute, Nov 12, 1992
: This file was modified by Yiota Poirazi ( on April 18, 2001 to account for the sharp
: Ca++ spike repolarization observed in: Golding, N. Jung H-Y., Mickus T. and Spruston N
: "Dendritic Calcium Spike Initiation and Repolarization are controlled by distinct potassium channel
: subtypes in CA1 pyramidal neurons". J. of Neuroscience 19(20) 8789-8798, 1999.
:  factor 10000 is replaced by 10000/18 needed in ca entry
:  taur --rate of calcium removal-- is replaced by taur*7 (7 times faster) 


	USEION ca READ ica, cai WRITE cai	
        RANGE ca
	GLOBAL depth,cainf,taur

	(molar) = (1/liter)			: moles do not appear in units
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	(msM)	= (ms mM)
	FARADAY = (faraday) (coulomb)

	depth	= .1	(um)		: depth of shell
	taur	= 200	(ms)		: rate of calcium removal
	cainf	= 100e-6(mM)
	cai		(mM)

	ca		(mM) 

	ca = cainf

	ica		(mA/cm2)
	drive_channel	(mM/ms)
	SOLVE state METHOD euler


	drive_channel =  - (10000) * ica / (2 * FARADAY * depth)
	if (drive_channel <= 0.) { drive_channel = 0.  }   : cannot pump inward 
	ca' = drive_channel/18 + (cainf-ca)/(taur*7)
      : ca' = drive_channel/20 + (cainf -ca)/(taur*9)

	cai = ca

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