A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP

摘要

Author summary Storing memory traces in the brain is essential for learning and memory formation, and it occurs through synaptic plasticity processes. Timing-dependent Long-Term Potentiation (t-LTP) is a physiologically relevant type of synaptic plasticity that results from the 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 patterns of combined pre- and postsynaptic activity that recruit distinct synaptic growth processes underlying t-LTP. The protein Brain-Derived Neurotrophic Factor (BDNF) is released at synapses and mediates synaptic plasticity in response to specific patterns of t-LTP stimulation in the theta frequency band, while other patterns 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 (70 repeats of pairing 1 presynaptic with 1 postsynaptic AP) and BDNF-dependent 1:4 t-LTP (25 repeats of pairing 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 important to counteract neurodegenerative diseases.