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Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism
Shiyu Tang1, Elizabeth M Powell2,3, Wenjun Zhu1
11 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Molecular Imaging
|February 26, 2019
Summary
Mice with altered MET gene function show impaired somatosensory thalamocortical network connectivity and neurotransmission, potentially modeling autism spectrum disorder (ASD) neural changes.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- The MET gene, encoding a tyrosine kinase receptor, is linked to autism spectrum disorder (ASD) susceptibility.
- Altered MET function in mice provides a model for investigating neural circuit changes in ASD.
- Somatosensory processing alterations are common in ASD, highlighting the importance of the somatosensory thalamocortical system.
Purpose of the Study:
- To investigate the impact of kinase-inactive MET gene alterations on somatosensory thalamocortical circuitry in mice.
- To examine neuronal connectivity and neurotransmission using advanced neuroimaging techniques.
- To explore sex-specific differences in brain network function and neurochemistry.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) to assess large-scale network connectivity.
- In vivo high-resolution proton magnetic resonance spectroscopy (1H-MRS) to analyze neurotransmitter balance (glutamate/GABA).
- Comparison of wild-type, heterozygous Met-Emx1, and homozygous Met-Emx1 mice, with analysis of sex-specific effects.
Main Results:
- Met-Emx1 mice exhibited impaired maturation of somatosensory network connectivity compared to wild-type controls.
- Significant sex × genotype interactions were found in both network connectivity and glutamate/GABA balance.
- Female Met-Emx1 brains showed altered connectivity and neurotransmitter balance in the somatosensory thalamocortical system.
Conclusions:
- Aberrant functioning of the somatosensory thalamocortical system is implicated in the behavioral phenotypes observed in Met-Emx1 mice.
- The MET gene plays a crucial role in the development and function of neural circuits relevant to ASD.
- Sex-specific mechanisms may underlie MET's influence on brain development and sensory processing.
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