Solinas et al. 2019
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A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP

Authors: Sergio M. G. Solinas1,2, Elke Edelmann3,4, Volkmar Leßmann3,4, Michele Migliore1

Author information: 1Istitute of Biophysics, National Research Council, Palermo, Italy, 2 Institute of Neuroinformatics, University of Zurich and ETH Zurich, Zurich, Switzerland, 3Institute of Physiology, Otto-von-Guericke-University, Medical Faculty, Magdeburg, Germany, 4Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany.

Corresponding author: Michele Migliore ( )

Journal: Plos Computational Biology

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Citation: 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


Licence: the Creative Commons Attribution (CC BY) license  applies for all files. Under this Open Access license anyone  may copy, distribute, or reuse the files as long as the authors and the original source are properly cited.

Across the mammalian nervous system, neurotrophins control synaptic plasticity, neuromodulation, and neuronal growth. The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is known to promote structural and functional synaptic plasticity in the hippocampus, the cerebral cortex, and many other brain areas. In recent years, a wealth of data has been accumulated revealing the paramount importance of BDNF for neuronal function. BDNF signaling gives rise to multiple complex signaling pathways that mediate neuronal survival and differentiation during development, and formation of new memories. These different roles of BDNF for neuronal function have essential consequences if BDNF signaling in the brain is reduced. Thus, BDNF knock-out mice or mice that are deficient in BDNF receptor signaling via TrkB and p75 receptors show deficits in neuronal development, synaptic plasticity, and memory formation. Accordingly, BDNF signaling dysfunctions are associated with many neurological and neurodegenerative conditions including Alzheimer's and Huntington's disease. However, despite the widespread implications of BDNF-dependent signaling in synaptic plasticity in healthy and pathological conditions, the interplay of the involved different biochemical pathways at the synaptic level remained mostly unknown. In this paper, we investigated the role of BDNF/TrkB signaling in spike-timing dependent plasticity (STDP) in rodent hippocampus CA1 pyramidal cells, by implementing the first subcellular model of BDNF regulated, spike timing-dependent long-term potentiation (t-LTP). The model is based on previously published experimental findings on STDP and accounts for the observed magnitude, time course, stimulation pattern and BDNF-dependence of t-LTP. It allows interpreting the main experimental findings concerning specific biomolecular processes, and it can be expanded to take into account more detailed biochemical reactions. The results point out a few predictions on how to enhance LTP induction in such a way to rescue or improve cognitive functions under pathological conditions.

Model and data: the model and the data used in the paper are available at the links reported in the sections below