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Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons
Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP(3)) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP(3)K-A binds to F-actin in an act...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884490/ https://www.ncbi.nlm.nih.gov/pubmed/29617377 http://dx.doi.org/10.1371/journal.pone.0193859 |
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author | Choi, Byungil Lee, Hyun Woo Mo, Seojung Kim, Jin Yong Kim, Hyun Wook Rhyu, Im Joo Hong, Eunhwa Lee, Yeon Kyung Choi, June-Seek Kim, Chong-Hyun Kim, Hyun |
author_facet | Choi, Byungil Lee, Hyun Woo Mo, Seojung Kim, Jin Yong Kim, Hyun Wook Rhyu, Im Joo Hong, Eunhwa Lee, Yeon Kyung Choi, June-Seek Kim, Chong-Hyun Kim, Hyun |
author_sort | Choi, Byungil |
collection | PubMed |
description | Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP(3)) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP(3)K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP(3)K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus. In the present study, to further elucidate the role of IP(3)K-A in the brain, we developed a transgenic (Tg) mouse line in which IP(3)K-A is conditionally overexpressed approximately 3-fold in the excitatory neurons of forebrain regions, including the hippocampus. The Tg mice showed an increase in both presynaptic release probability of evoked responses, along with bigger synaptic vesicle pools, and miniature excitatory postsynaptic current amplitude, although the spine density or the expression levels of the postsynaptic density-related proteins NR2B, synaptotagmin 1, and PSD-95 were not affected. Hippocampal-dependent learning and memory tasks, including novel object recognition and radial arm maze tasks, were partially impaired in Tg mice. Furthermore, (R,S)-3,5-dihydroxyphenylglycine-induced metabotropic glutamate receptor long-term depression was inhibited in Tg mice and this inhibition was dependent on protein kinase C but not on the IP(3) receptor. Long-term potentiation and depression dependent on N-methyl-d-aspartate receptor were marginally affected in Tg mice. In summary, this study shows that overexpressed IP(3)K-A plays a role in some forms of hippocampus-dependent learning and memory tasks as well as in synaptic transmission and plasticity by regulating both presynaptic and postsynaptic functions. |
format | Online Article Text |
id | pubmed-5884490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58844902018-04-13 Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons Choi, Byungil Lee, Hyun Woo Mo, Seojung Kim, Jin Yong Kim, Hyun Wook Rhyu, Im Joo Hong, Eunhwa Lee, Yeon Kyung Choi, June-Seek Kim, Chong-Hyun Kim, Hyun PLoS One Research Article Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP(3)) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP(3)K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP(3)K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus. In the present study, to further elucidate the role of IP(3)K-A in the brain, we developed a transgenic (Tg) mouse line in which IP(3)K-A is conditionally overexpressed approximately 3-fold in the excitatory neurons of forebrain regions, including the hippocampus. The Tg mice showed an increase in both presynaptic release probability of evoked responses, along with bigger synaptic vesicle pools, and miniature excitatory postsynaptic current amplitude, although the spine density or the expression levels of the postsynaptic density-related proteins NR2B, synaptotagmin 1, and PSD-95 were not affected. Hippocampal-dependent learning and memory tasks, including novel object recognition and radial arm maze tasks, were partially impaired in Tg mice. Furthermore, (R,S)-3,5-dihydroxyphenylglycine-induced metabotropic glutamate receptor long-term depression was inhibited in Tg mice and this inhibition was dependent on protein kinase C but not on the IP(3) receptor. Long-term potentiation and depression dependent on N-methyl-d-aspartate receptor were marginally affected in Tg mice. In summary, this study shows that overexpressed IP(3)K-A plays a role in some forms of hippocampus-dependent learning and memory tasks as well as in synaptic transmission and plasticity by regulating both presynaptic and postsynaptic functions. Public Library of Science 2018-04-04 /pmc/articles/PMC5884490/ /pubmed/29617377 http://dx.doi.org/10.1371/journal.pone.0193859 Text en © 2018 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Choi, Byungil Lee, Hyun Woo Mo, Seojung Kim, Jin Yong Kim, Hyun Wook Rhyu, Im Joo Hong, Eunhwa Lee, Yeon Kyung Choi, June-Seek Kim, Chong-Hyun Kim, Hyun Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title | Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title_full | Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title_fullStr | Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title_full_unstemmed | Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title_short | Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons |
title_sort | inositol 1,4,5-trisphosphate 3-kinase a overexpressed in mouse forebrain modulates synaptic transmission and mglur-ltd of ca1 pyramidal neurons |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884490/ https://www.ncbi.nlm.nih.gov/pubmed/29617377 http://dx.doi.org/10.1371/journal.pone.0193859 |
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