Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.

The mechanisms of long-term synaptic maintenance are a key component to understanding the mechanism of long-term memory. From biological experiments, a hypothesis arose that repetitive stimuli with appropriate intervals are essential to maintain new synapses for periods of longer than a few days. We...

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Autores principales:	Hiromu Takizawa, Noriko Hiroi, Akira Funahashi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13263eaaf842449b99d9ceb2241ffac0
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spelling	oai:doaj.org-article:13263eaaf842449b99d9ceb2241ffac02021-11-18T08:04:25ZMathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.1932-620310.1371/journal.pone.0051000https://doaj.org/article/13263eaaf842449b99d9ceb2241ffac02012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284653/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The mechanisms of long-term synaptic maintenance are a key component to understanding the mechanism of long-term memory. From biological experiments, a hypothesis arose that repetitive stimuli with appropriate intervals are essential to maintain new synapses for periods of longer than a few days. We successfully reproduce the time-course of relative numbers of synapses with our mathematical model in the same conditions as biological experiments, which used Adenosine-3', 5'-cyclic monophosphorothioate, Sp-isomer (Sp-cAMPS) as external stimuli. We also reproduce synaptic maintenance responsiveness to intervals of Sp-cAMPS treatment accompanied by PKA activation. The model suggests a possible mechanism of sustainable synaptogenesis which consists of two steps. First, the signal transduction from an external stimulus triggers the synthesis of a new signaling protein. Second, the new signaling protein is required for the next signal transduction with the same stimuli. As a result, the network component is modified from the first network, and a different signal is transferred which triggers the synthesis of another new signaling molecule. We refer to this hypothetical mechanism as network succession. We build our model on the basis of two hypotheses: (1) a multi-step network succession induces downregulation of SSH and COFILIN gene expression, which triggers the production of stable F-actin; (2) the formation of a complex of stable F-actin with Drebrin at PSD is the critical mechanism to achieve long-term synaptic maintenance. Our simulation shows that a three-step network succession is sufficient to reproduce sustainable synapses for a period longer than 14 days. When we change the network structure to a single step network, the model fails to follow the exact condition of repetitive signals to reproduce a sufficient number of synapses. Another advantage of the three-step network succession is that this system indicates a greater tolerance of parameter changes than the single step network.Hiromu TakizawaNoriko HiroiAkira FunahashiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51000 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiromu Takizawa Noriko Hiroi Akira Funahashi Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
description	The mechanisms of long-term synaptic maintenance are a key component to understanding the mechanism of long-term memory. From biological experiments, a hypothesis arose that repetitive stimuli with appropriate intervals are essential to maintain new synapses for periods of longer than a few days. We successfully reproduce the time-course of relative numbers of synapses with our mathematical model in the same conditions as biological experiments, which used Adenosine-3', 5'-cyclic monophosphorothioate, Sp-isomer (Sp-cAMPS) as external stimuli. We also reproduce synaptic maintenance responsiveness to intervals of Sp-cAMPS treatment accompanied by PKA activation. The model suggests a possible mechanism of sustainable synaptogenesis which consists of two steps. First, the signal transduction from an external stimulus triggers the synthesis of a new signaling protein. Second, the new signaling protein is required for the next signal transduction with the same stimuli. As a result, the network component is modified from the first network, and a different signal is transferred which triggers the synthesis of another new signaling molecule. We refer to this hypothetical mechanism as network succession. We build our model on the basis of two hypotheses: (1) a multi-step network succession induces downregulation of SSH and COFILIN gene expression, which triggers the production of stable F-actin; (2) the formation of a complex of stable F-actin with Drebrin at PSD is the critical mechanism to achieve long-term synaptic maintenance. Our simulation shows that a three-step network succession is sufficient to reproduce sustainable synapses for a period longer than 14 days. When we change the network structure to a single step network, the model fails to follow the exact condition of repetitive signals to reproduce a sufficient number of synapses. Another advantage of the three-step network succession is that this system indicates a greater tolerance of parameter changes than the single step network.
format	article
author	Hiromu Takizawa Noriko Hiroi Akira Funahashi
author_facet	Hiromu Takizawa Noriko Hiroi Akira Funahashi
author_sort	Hiromu Takizawa
title	Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
title_short	Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
title_full	Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
title_fullStr	Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
title_full_unstemmed	Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
title_sort	mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/13263eaaf842449b99d9ceb2241ffac0
work_keys_str_mv	AT hiromutakizawa mathematicalmodelingofsustainablesynaptogenesisbyrepetitivestimulisuggestssignalingmechanismsinvivo AT norikohiroi mathematicalmodelingofsustainablesynaptogenesisbyrepetitivestimulisuggestssignalingmechanismsinvivo AT akirafunahashi mathematicalmodelingofsustainablesynaptogenesisbyrepetitivestimulisuggestssignalingmechanismsinvivo
_version_	1718422212114907136

Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.

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