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]
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;
/* Sets nseg in each section to an odd value
   so that its segments are no longer than 
     d_lambda x the AC length constant
   at frequency freq in that section.

   Be sure to specify your own Ra and cm before calling geom_nseg()

   To understand why this works, 
   and the advantages of using an odd value for nseg,
   see  Hines, M.L. and Carnevale, N.T.
        NEURON: a tool for neuroscientists.
        The Neuroscientist 7:123-135, 2001.
*/

// these are reasonable values for most models
freq = 100      // Hz, frequency at which AC length constant will be computed
d_lambda = 0.1

func lambda_f() { local i, x1, x2, d1, d2, lam
        if (n3d() < 2) {
                return 1e5*sqrt(diam/(4*PI*$1*Ra*cm))
        }
// above was too inaccurate with large variation in 3d diameter
// so now we use all 3-d points to get a better approximate lambda
        x1 = arc3d(0)
        d1 = diam3d(0)
        lam = 0
        for i=1, n3d()-1 {
                x2 = arc3d(i)
                d2 = diam3d(i)
                lam += (x2 - x1)/sqrt(d1 + d2)
                x1 = x2   d1 = d2
        }
        //  length of the section in units of lambda
        lam *= sqrt(2) * 1e-5*sqrt(4*PI*$1*Ra*cm)

        return L/lam
}

proc geom_nseg() {
    soma area(0.5) // make sure diam reflects 3d points
    forall { nseg = int((L/(d_lambda*lambda_f(freq))+0.9)/2)*2 + 1  }
}


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