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 2024-01-19T23:02:05Z 2024-01-19T23:02:05Z 2021-09-03 2018-04-04 1932-6203 https://pubs.kist.re.kr/handle/201004/121495 Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP3) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP3K-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. IP3K-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 IP3K-A in the brain, we developed a transgenic (Tg) mouse line in which IP3K-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 IP3 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 IP3K-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. English PUBLIC LIBRARY SCIENCE METABOTROPIC GLUTAMATE-RECEPTOR LONG-TERM DEPRESSION PROTEIN-KINASE-C DHPG-INDUCED LTD GYRUS IN-VITRO SIGNAL-TRANSDUCTION RAT HIPPOCAMPUS BEHAVIORAL FLEXIBILITY ENDOPLASMIC-RETICULUM DENDRITIC SPINES Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons Article 10.1371/journal.pone.0193859 1 PLOS ONE, v.13, no.4 PLOS ONE 13 4 scie scopus 000429203800015 2-s2.0-85045064216 Multidisciplinary Sciences Science & Technology - Other Topics Article METABOTROPIC GLUTAMATE-RECEPTOR LONG-TERM DEPRESSION PROTEIN-KINASE-C DHPG-INDUCED LTD GYRUS IN-VITRO SIGNAL-TRANSDUCTION RAT HIPPOCAMPUS BEHAVIORAL FLEXIBILITY ENDOPLASMIC-RETICULUM DENDRITIC SPINES