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

Solinas, Sergio M G; Edelmann, Elke; Leßmann, Volkmar; Migliore, Michele (2019). A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP. PLoS Computational Biology, 15(4):e1006975.

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Neuroinformatics
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Ecology, Evolution, Behavior and Systematics
Physical Sciences > Modeling and Simulation
Physical Sciences > Ecology
Life Sciences > Molecular Biology
Life Sciences > Genetics
Life Sciences > Cellular and Molecular Neuroscience
Physical Sciences > Computational Theory and Mathematics
Uncontrolled Keywords:Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience
Language:English
Date:24 April 2019
Deposited On:14 Feb 2020 10:19
Last Modified:23 Oct 2024 01:36
Publisher:Public Library of Science (PLoS)
ISSN:1553-734X
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pcbi.1006975
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  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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