Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety
Summary: The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoam...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222010720 |
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| author | Daiki X. Sato Yukiko U. Inoue Nahoko Kuga Satoko Hattori Kensaku Nomoto Yuki Morimoto Giovanni Sala Hideo Hagihara Takefumi Kikusui Takuya Sasaki Yuji Ikegaya Tsuyoshi Miyakawa Takayoshi Inoue Masakado Kawata |
| author_facet | Daiki X. Sato Yukiko U. Inoue Nahoko Kuga Satoko Hattori Kensaku Nomoto Yuki Morimoto Giovanni Sala Hideo Hagihara Takefumi Kikusui Takuya Sasaki Yuji Ikegaya Tsuyoshi Miyakawa Takayoshi Inoue Masakado Kawata |
| author_sort | Daiki X. Sato |
| collection | DOAJ |
| description | Summary: The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors. |
| first_indexed | 2024-12-10T15:57:43Z |
| format | Article |
| id | doaj.art-003238d0a6fe457aabd60eabff60351f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-10T15:57:43Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-003238d0a6fe457aabd60eabff60351f2022-12-22T01:42:33ZengElsevieriScience2589-00422022-08-01258104800Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxietyDaiki X. Sato0Yukiko U. Inoue1Nahoko Kuga2Satoko Hattori3Kensaku Nomoto4Yuki Morimoto5Giovanni Sala6Hideo Hagihara7Takefumi Kikusui8Takuya Sasaki9Yuji Ikegaya10Tsuyoshi Miyakawa11Takayoshi Inoue12Masakado Kawata13Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan; Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, JapanGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, JapanDivision of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Physiology, Dokkyo Medical University, Mibu, Tochigi, 321-0293, JapanDepartment of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, JapanDivision of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, JapanDivision of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Animal Science and Biotechnology, Azabu University, Sagamihara, Kanagawa, JapanGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, JapanGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, 1-4 Yamadaoka, Suita City, Osaka 565-0871, Japan; Institute for AI and Beyond, The University of Tokyo, Tokyo 113-0033, JapanDivision of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, JapanGraduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan; Corresponding authorSummary: The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.http://www.sciencedirect.com/science/article/pii/S2589004222010720Behavior geneticsMolecular GeneticsMolecular mechanism of behaviorEvolutionary biology |
| spellingShingle | Daiki X. Sato Yukiko U. Inoue Nahoko Kuga Satoko Hattori Kensaku Nomoto Yuki Morimoto Giovanni Sala Hideo Hagihara Takefumi Kikusui Takuya Sasaki Yuji Ikegaya Tsuyoshi Miyakawa Takayoshi Inoue Masakado Kawata Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety iScience Behavior genetics Molecular Genetics Molecular mechanism of behavior Evolutionary biology |
| title | Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety |
| title_full | Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety |
| title_fullStr | Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety |
| title_full_unstemmed | Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety |
| title_short | Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety |
| title_sort | humanized substitutions of vmat1 in mice alter amygdala dependent behaviors associated with the evolution of anxiety |
| topic | Behavior genetics Molecular Genetics Molecular mechanism of behavior Evolutionary biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222010720 |
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