Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models
In vivo optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from in vivo imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fra...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00412/full |
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| author | Nobuhiro Nakai Toru Takumi Junichi Nakai Junichi Nakai Junichi Nakai Junichi Nakai Masaaki Sato Masaaki Sato Masaaki Sato |
| author_facet | Nobuhiro Nakai Toru Takumi Junichi Nakai Junichi Nakai Junichi Nakai Junichi Nakai Masaaki Sato Masaaki Sato Masaaki Sato |
| author_sort | Nobuhiro Nakai |
| collection | DOAJ |
| description | In vivo optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from in vivo imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fragile X syndrome, Rett syndrome, and Angelman syndrome, which are caused by genetic abnormalities of FMR1, MECP2, and UBE3A, as well as disorders caused by copy number variations (15q11-13 duplication and 22q11.2 deletion) and BTBR mice as an inbred strain model of autism spectrum disorder (ASD). Most studies visualize the structural and functional responsiveness of cerebral cortical neurons to sensory stimuli and the developmental and experience-dependent changes in these responses as a model of brain functions affected by these disorders. The optical imaging techniques include two-photon microscopy of fluorescently labeled dendritic spines or neurons loaded with fluorescent calcium indicators and macroscopic imaging of cortical activity using calcium indicators, voltage-sensitive dyes or intrinsic optical signals. Studies have revealed alterations in the density, stability, and turnover of dendritic spines, aberrant cortical sensory responses, impaired inhibitory function, and concomitant failure of circuit maturation as common causes for neurological deficits. Mechanistic hypotheses derived from in vivo imaging also provide new directions for therapeutic interventions. For instance, it was recently demonstrated that early postnatal administration of a selective serotonin reuptake inhibitor (SSRI) restores impaired cortical inhibitory function and ameliorates the aberrant social behaviors in a mouse model of ASD. We discuss the potential use of SSRIs for treating ASDs in light of these findings. |
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| format | Article |
| id | doaj.art-ac1e5954fca54bfa98ad02e6707a5293 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-12T06:30:12Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-ac1e5954fca54bfa98ad02e6707a52932022-12-22T00:34:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-06-011210.3389/fnins.2018.00412371381Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse ModelsNobuhiro Nakai0Toru Takumi1Junichi Nakai2Junichi Nakai3Junichi Nakai4Junichi Nakai5Masaaki Sato6Masaaki Sato7Masaaki Sato8RIKEN Center for Brain Science, Wako, JapanRIKEN Center for Brain Science, Wako, JapanRIKEN Center for Brain Science, Wako, JapanRIKEN Center for Advanced Intelligence Project, Tokyo, JapanGraduate School of Science and Engineering, Saitama University, Saitama, JapanBrain and Body System Science Institute, Saitama University, Saitama, JapanRIKEN Center for Brain Science, Wako, JapanGraduate School of Science and Engineering, Saitama University, Saitama, JapanBrain and Body System Science Institute, Saitama University, Saitama, JapanIn vivo optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from in vivo imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fragile X syndrome, Rett syndrome, and Angelman syndrome, which are caused by genetic abnormalities of FMR1, MECP2, and UBE3A, as well as disorders caused by copy number variations (15q11-13 duplication and 22q11.2 deletion) and BTBR mice as an inbred strain model of autism spectrum disorder (ASD). Most studies visualize the structural and functional responsiveness of cerebral cortical neurons to sensory stimuli and the developmental and experience-dependent changes in these responses as a model of brain functions affected by these disorders. The optical imaging techniques include two-photon microscopy of fluorescently labeled dendritic spines or neurons loaded with fluorescent calcium indicators and macroscopic imaging of cortical activity using calcium indicators, voltage-sensitive dyes or intrinsic optical signals. Studies have revealed alterations in the density, stability, and turnover of dendritic spines, aberrant cortical sensory responses, impaired inhibitory function, and concomitant failure of circuit maturation as common causes for neurological deficits. Mechanistic hypotheses derived from in vivo imaging also provide new directions for therapeutic interventions. For instance, it was recently demonstrated that early postnatal administration of a selective serotonin reuptake inhibitor (SSRI) restores impaired cortical inhibitory function and ameliorates the aberrant social behaviors in a mouse model of ASD. We discuss the potential use of SSRIs for treating ASDs in light of these findings.https://www.frontiersin.org/article/10.3389/fnins.2018.00412/fulltwo-photon imagingcalcium imagingautism spectrum disorders (ASDs)dendritic spinesexcitatory-inhibitory balanceserotonin |
| spellingShingle | Nobuhiro Nakai Toru Takumi Junichi Nakai Junichi Nakai Junichi Nakai Junichi Nakai Masaaki Sato Masaaki Sato Masaaki Sato Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models Frontiers in Neuroscience two-photon imaging calcium imaging autism spectrum disorders (ASDs) dendritic spines excitatory-inhibitory balance serotonin |
| title | Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models |
| title_full | Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models |
| title_fullStr | Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models |
| title_full_unstemmed | Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models |
| title_short | Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models |
| title_sort | common defects of spine dynamics and circuit function in neurodevelopmental disorders a systematic review of findings from in vivo optical imaging of mouse models |
| topic | two-photon imaging calcium imaging autism spectrum disorders (ASDs) dendritic spines excitatory-inhibitory balance serotonin |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00412/full |
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