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.
Model Type: Neuron or other electrically excitable cell; Synapse; Dendrite
Region(s) or Organism(s): Hippocampus
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents: I Na,t; I_KD; I K; I h; I A; I Calcium
Transmitters: Glutamate
Model Concept(s): Facilitation; Long-term Synaptic Plasticity; Short-term Synaptic Plasticity; STDP
Simulation Environment: NEURON
Implementer(s): Solinas, Sergio [solinas at unipv.it]; Migliore, Michele [Michele.Migliore at Yale.edu]
References:
Solinas SMG, Edelmann E, Leßmann V, Migliore M. (2019). A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP. PLoS computational biology. 15 [PubMed]