Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice
Importin α3 (Gene: Kpna3, the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP)...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.905991/full |
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| author | Yoshiatsu Aomine Yoshiatsu Aomine Koki Sakurai Koki Sakurai Tom Macpherson Tom Macpherson Takaaki Ozawa Takaaki Ozawa Yoichi Miyamoto Yoshihiro Yoneda Masahiro Oka Takatoshi Hikida Takatoshi Hikida |
| author_facet | Yoshiatsu Aomine Yoshiatsu Aomine Koki Sakurai Koki Sakurai Tom Macpherson Tom Macpherson Takaaki Ozawa Takaaki Ozawa Yoichi Miyamoto Yoshihiro Yoneda Masahiro Oka Takatoshi Hikida Takatoshi Hikida |
| author_sort | Yoshiatsu Aomine |
| collection | DOAJ |
| description | Importin α3 (Gene: Kpna3, the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP) in the KPNA3 gene are associated with the occurrence of several psychiatric disorders accompanied by abnormal reward-related behavior, including schizophrenia, major depression, and substance addiction. However, the precise roles of importin α3 in controlling reward processing and motivation are still unclear. In this study, we evaluated the behavioral effects of Kpna3 knockout (KO) in mice on performance in touchscreen operant chamber-based tasks evaluating simple (fixed-ratio) and effortful (progressive-ratio) reward-seeking behaviors. While Kpna3 KO mice showed no significant differences in operant reward learning on a fixed-ratio schedule, they demonstrated significantly increased motivation (increased break point) to instrumentally respond for sucrose on a progressive-ratio schedule. We additionally measured the number of c-Fos-positive cells, a marker of neural activity, in 20 regions of the brain and identified a network of brain regions based on their interregional correlation coefficients. Network and graph-theoretic analyses suggested that Kpna3 deficiency enhanced overall interregional functional connectivity. These findings suggest the importance of Kpna3 in motivational control and indicate that Kpna3 KO mice may be an attractive line for modeling motivational abnormalities associated with several psychiatric disorders. |
| first_indexed | 2024-04-12T12:37:11Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-12T12:37:11Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-5950c7e75ce74768bb30982df01a13252022-12-22T03:32:52ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-06-011610.3389/fnins.2022.905991905991Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in MiceYoshiatsu Aomine0Yoshiatsu Aomine1Koki Sakurai2Koki Sakurai3Tom Macpherson4Tom Macpherson5Takaaki Ozawa6Takaaki Ozawa7Yoichi Miyamoto8Yoshihiro Yoneda9Masahiro Oka10Takatoshi Hikida11Takatoshi Hikida12Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, JapanDepartment of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, JapanDepartment of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, JapanDepartment of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, JapanDepartment of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, JapanNational Institutes for Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, JapanLaboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, JapanLaboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, JapanDepartment of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanImportin α3 (Gene: Kpna3, the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP) in the KPNA3 gene are associated with the occurrence of several psychiatric disorders accompanied by abnormal reward-related behavior, including schizophrenia, major depression, and substance addiction. However, the precise roles of importin α3 in controlling reward processing and motivation are still unclear. In this study, we evaluated the behavioral effects of Kpna3 knockout (KO) in mice on performance in touchscreen operant chamber-based tasks evaluating simple (fixed-ratio) and effortful (progressive-ratio) reward-seeking behaviors. While Kpna3 KO mice showed no significant differences in operant reward learning on a fixed-ratio schedule, they demonstrated significantly increased motivation (increased break point) to instrumentally respond for sucrose on a progressive-ratio schedule. We additionally measured the number of c-Fos-positive cells, a marker of neural activity, in 20 regions of the brain and identified a network of brain regions based on their interregional correlation coefficients. Network and graph-theoretic analyses suggested that Kpna3 deficiency enhanced overall interregional functional connectivity. These findings suggest the importance of Kpna3 in motivational control and indicate that Kpna3 KO mice may be an attractive line for modeling motivational abnormalities associated with several psychiatric disorders.https://www.frontiersin.org/articles/10.3389/fnins.2022.905991/fullimportin αKPNAprogressive ratio schedulec-fosfunctional connectivitybrain network |
| spellingShingle | Yoshiatsu Aomine Yoshiatsu Aomine Koki Sakurai Koki Sakurai Tom Macpherson Tom Macpherson Takaaki Ozawa Takaaki Ozawa Yoichi Miyamoto Yoshihiro Yoneda Masahiro Oka Takatoshi Hikida Takatoshi Hikida Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice Frontiers in Neuroscience importin α KPNA progressive ratio schedule c-fos functional connectivity brain network |
| title | Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice |
| title_full | Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice |
| title_fullStr | Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice |
| title_full_unstemmed | Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice |
| title_short | Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice |
| title_sort | importin α3 kpna3 deficiency augments effortful reward seeking behavior in mice |
| topic | importin α KPNA progressive ratio schedule c-fos functional connectivity brain network |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.905991/full |
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