biostudies-literatureKim MGNational Research Foundation of Korea72https://www.ebi.ac.uk/biostudies/studies/S-EPMC7206715biostudies-literatureUnknown13(1)Inositol phosphate metabolism has emerged as one of the key players in synaptic transmission. Previous studies have shown that the deletion of inositol hexakisphosphate kinase 1 (IP6K1), which is responsible for inositol pyrophosphate biosynthesis, alters probability of presynaptic vesicle release and short-term facilitation of glutamatergic synapses in mouse hippocampus. However, the behavioral and cognitive functions regulated by IP6K1 remain largely elusive. In this study, IP6K1-knockout mice exhibited decreased prepulse inhibition with no defects in Y-maze and elevated plus maze tests. Interestingly, IP6K1 knockout led to impaired short-term memory formation in a contextual fear memory retrieval test with no effect on long-term memory. Further, both hippocampal long-term potentiation and long-term depression in IP6K1-knockout mice were similar to those in the wild-type control. Taken together, the findings in this study suggest the physiological roles of IP6K1 and the associated inositol pyrophosphate metabolism in regulating sensorimotor gating as well as short-term memory.Molecular brainInositol hexakisphosphate kinase-1 is a key mediator of prepulse inhibition and short-term fear memory.PMC7206715NRF-2018R1A5A1024261NRF-2017R1A2B4006535NRF-2019M3C7A1031742NRF-2018R1A2B2005913Kim SChung CPark HZhang SPark SJKim MGfalseInositol hexakisphosphate kinase-1 is a key mediator of prepulse inhibition and short-term fear memory.Inositol phosphate metabolism has emerged as one of the key players in synaptic transmission. Previous studies have shown that the deletion of inositol hexakisphosphate kinase 1 (IP6K1), which is responsible for inositol pyrophosphate biosynthesis, alters probability of presynaptic vesicle release and short-term facilitation of glutamatergic synapses in mouse hippocampus. However, the behavioral and cognitive functions regulated by IP6K1 remain largely elusive. In this study, IP6K1-knockout mice exhibited decreased prepulse inhibition with no defects in Y-maze and elevated plus maze tests. Interestingly, IP6K1 knockout led to impaired short-term memory formation in a contextual fear memory retrieval test with no effect on long-term memory. Further, both hippocampal long-term potentiation and long-term depression in IP6K1-knockout mice were similar to those in the wild-type control. Taken together, the findings in this study suggest the physiological roles of IP6K1 and the associated inositol pyrophosphate metabolism in regulating sensorimotor gating as well as short-term memory.2020-01-01T00:00:00Z2020 May2024-11-09T05:12:16.703Z2020-05-22T20:09:00ZS-EPMC72067153238105110.1186/s13041-020-00615-3