1. Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Mouse Model of Autism
- Author
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Elizabeth M. Powell, Su Xu, Shiyu Tang, Fu-Sun Lo, Wenjun Zhu, and Reha S. Erzurumlu
- Subjects
Male ,Autism Spectrum Disorder ,resting-state functional magnetic resonance imaging ,Somatosensory system ,Receptor tyrosine kinase ,Mice ,GABA ,0302 clinical medicine ,Thalamus ,lcsh:QH301-705.5 ,gamma-Aminobutyric Acid ,Brain Mapping ,0303 health sciences ,medicine.diagnostic_test ,biology ,Glutamate receptor ,Proto-Oncogene Proteins c-met ,met null mice ,Condensed Matter Physics ,Magnetic Resonance Imaging ,lcsh:R855-855.5 ,Molecular Medicine ,Female ,Research Article ,Biotechnology ,lcsh:Medical technology ,Biomedical Engineering ,autism ,somatosensory thalamocortical system ,Neurotransmission ,03 medical and health sciences ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,030304 developmental biology ,brain network ,fungi ,Somatosensory Cortex ,medicine.disease ,magnetic resonance spectroscopy ,Mice, Inbred C57BL ,Disease Models, Animal ,lcsh:Biology (General) ,Forebrain ,biology.protein ,Autism ,Functional magnetic resonance imaging ,Neuroscience ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2019