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]
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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
                            
TITLE na3
: Na current for axon. No slow inact.
: M.Migliore Jul. 1997

NEURON {
	SUFFIX nax
	USEION na READ ena WRITE ina
	RANGE  gbar
	GLOBAL minf, hinf, mtau, htau,thinf, qinf
}

PARAMETER {
	gbar = 0.010   	(mho/cm2)	
								
	tha  =  -30	(mV)		: v 1/2 for act	
	qa   = 7.2	(mV)		: act slope (4.5)		
	Ra   = 0.4	(/ms)		: open (v)		
	Rb   = 0.124 	(/ms)		: close (v)		

	thi1  = -45	(mV)		: v 1/2 for inact 	
	thi2  = -45 	(mV)		: v 1/2 for inact 	
	qd   = 1.5	(mV)	        : inact tau slope
	qg   = 1.5      (mV)
	mmin=0.02	
	hmin=0.5			
	q10=2
	Rg   = 0.01 	(/ms)		: inact recov (v) 	
	Rd   = .03 	(/ms)		: inact (v)	

	thinf  = -50 	(mV)		: inact inf slope	
	qinf  = 4 	(mV)		: inact inf slope 

	ena		(mV)            : must be explicitly def. in hoc
	celsius
	v 		(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

ASSIGNED {
	ina 		(mA/cm2)
	thegna		(mho/cm2)
	minf 		hinf 		
	mtau (ms)	htau (ms) 	
}
 

STATE { m h}

BREAKPOINT {
        SOLVE states METHOD cnexp
        thegna = gbar*m*m*m*h
	ina = thegna * (v - ena)
} 

INITIAL {
	trates(v)
	m=minf  
	h=hinf
}

DERIVATIVE states {   
        trates(v)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
}

PROCEDURE trates(vm) {  
        LOCAL  a, b, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha,Ra,qa)
	b = trap0(-vm,-tha,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1,Rd,qd)
	b = trap0(-vm,-thi2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf)/qinf))
}

FUNCTION trap0(v,th,a,q) {
	if (fabs(v-th) > 1e-6) {
	        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
	} else {
	        trap0 = a * q
 	}
}