Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism. (2nd January 2019)

• Record Type: Journal Article
• Authors: Tang, Shiyu; Powell, Elizabeth M.; Zhu, Wenjun; Lo, Fu-Sun; Erzurumlu, Reha S.; Xu, Su
• Is Part Of: Molecular imaging. Volume 18(2019)
• Publication Date: 2019-01-02
• Subjects: autism -- resting-state functional magnetic resonance imaging -- magnetic resonance spectroscopy -- brain network -- somatosensory thalamocortical system -- met null mice -- GABA; Molecular diagnosis -- Periodicals; Diagnostic imaging -- Periodicals; Molecular biology -- Periodicals; Molecular diagnosis; Diagnostic imaging; Molecular biology; Periodicals; 616.075
• DOI: 10.1177/1536012118821034
• Languages: English
• ISSNs: 1535-3508

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.