STDP and BDNF in CA1 spines (Solinas et al. 2019)

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Accession:244412
Storing memory traces in the brain is essential for learning and memory formation. Memory traces are created by joint electrical activity in neurons that are interconnected by synapses and allow transferring electrical activity from a sending (presynaptic) to a receiving (postsynaptic) neuron. During learning, neurons that are co-active can tune synapses to become more effective. This process is called synaptic plasticity or long-term potentiation (LTP). Timing-dependent LTP (t-LTP) is a physiologically relevant type of synaptic plasticity that results from repeated sequential firing of action potentials (APs) in pre- and postsynaptic neurons. T-LTP is observed during learning in vivo and is a cellular correlate of memory formation. T-LTP can be elicited by different rhythms of synaptic activity that recruit distinct synaptic growth processes underlying t-LTP. The protein brain-derived neurotrophic factor (BDNF) is released at synapses and mediates synaptic growth in response to specific rhythms of t-LTP stimulation, while other rhythms mediate BDNF-independent t-LTP. Here, we developed a realistic computational model that accounts for our previously published experimental results of BDNF-independent 1:1 t-LTP (pairing of 1 presynaptic with 1 postsynaptic AP) and BDNF-dependent 1:4 t-LTP (pairing of 1 presynaptic with 4 postsynaptic APs). The model explains the magnitude and time course of both t-LTP forms and allows predicting t-LTP properties that result from altered BDNF turnover. Since BDNF levels are decreased in demented patients, understanding the function of BDNF in memory processes is of utmost importance to counteract Alzheimer’s disease.
Reference:
1 . Solinas SMG, Edelmann E, Leßmann V, Migliore M (2019) A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP. PLoS Comput Biol 15:e1006975 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse; Dendrite;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I_KD; I K; I h; I A; I Calcium;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Facilitation; Long-term Synaptic Plasticity; Short-term Synaptic Plasticity; STDP;
Implementer(s): Solinas, Sergio [solinas at unipv.it]; Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; NMDA; I Na,t; I A; I K; I h; I Calcium; I_KD; Glutamate;
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SolinasEtAl2019
mod_files
BDNF.mod
cad.mod
cagk.mod
cal2.mod
can2.mod
cat.mod
distr.mod *
ghknmda.mod
h.mod *
kadist.mod *
kaprox.mod *
kdrca1.mod *
na3n.mod *
naxn.mod *
netstims.mod *
RM_eCB.mod
Wghkampa_preML.mod
                            
TITLE nax
: Na current for axon. No slow inact.
: M.Migliore Jul. 1997
: added sh to account for higher threshold M.Migliore, Apr.2002

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

PARAMETER {
	sh   = 0	(mV)
	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,sh)
	m=minf  
	h=hinf
}

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

PROCEDURE trates(vm,sh2) {  
        LOCAL  a, b, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha+sh2,Ra,qa)
	b = trap0(-vm,-tha-sh2,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1+sh2,Rd,qd)
	b = trap0(-vm,-thi2-sh2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf-sh2)/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
 	}
}