Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism
MET , the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-01-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012118821034 |
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| author | Shiyu Tang PhD Elizabeth M. Powell PhD Wenjun Zhu MS Fu-Sun Lo MD Reha S. Erzurumlu PhD Su Xu PhD |
| author_facet | Shiyu Tang PhD Elizabeth M. Powell PhD Wenjun Zhu MS Fu-Sun Lo MD Reha S. Erzurumlu PhD Su Xu PhD |
| author_sort | Shiyu Tang PhD |
| collection | DOAJ |
| description | MET , the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met–Emx1 , and fully inactive homozygous Met–Emx1 mice. Met–Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met–Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met–Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met–Emx1 mice. |
| format | Article |
| id | doaj-art-7f137a8329f841a8a6ea17b378a4e416 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-7f137a8329f841a8a6ea17b378a4e4162025-01-02T23:12:07ZengSAGE PublishingMolecular Imaging1536-01212019-01-011810.1177/1536012118821034Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of AutismShiyu Tang PhD0Elizabeth M. Powell PhD1Wenjun Zhu MS2Fu-Sun Lo MD3Reha S. Erzurumlu PhD4Su Xu PhD5 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USAMET , the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met–Emx1 , and fully inactive homozygous Met–Emx1 mice. Met–Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met–Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met–Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met–Emx1 mice.https://doi.org/10.1177/1536012118821034 |
| spellingShingle | Shiyu Tang PhD Elizabeth M. Powell PhD Wenjun Zhu MS Fu-Sun Lo MD Reha S. Erzurumlu PhD Su Xu PhD Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism Molecular Imaging |
| title | Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism |
| title_full | Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism |
| title_fullStr | Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism |
| title_full_unstemmed | Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism |
| title_short | Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism |
| title_sort | altered forebrain functional connectivity and neurotransmission in a kinase inactive mouse model of autism |
| url | https://doi.org/10.1177/1536012118821034 |
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