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Abstract #0250

Functional connectivity is globally altered by schizophrenia-linked genes

Garth J Thompson1,2, Karen Perez De Arce3, Basavaraju G Sanganahalli1,2,4, Stephen M Strittmatter5, Thomas Biederer3, and Fahmeed Hyder1,2,4,6

1Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, 2Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, United States, 3Neuroscience, Tufts University School of Medicine, Boston, MA, United States, 4Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University, New Haven, CT, United States, 5Cellular Neuroscience, Neurodegeneration, and Repair Program, and Departments of Neurology and Neurobiology, Yale University School of Medicine, New Haven, CT, United States, 6Biomedical Engineering, Yale University, New Haven, CT, United States

Resting state fMRI shows increased global synchrony in schizophrenia at rest, but mechanisms remain speculative. We tested mice with knockout of SynCAM1 (related to synaptic organization), LRRTM1 (related to schizophrenia symptoms) and both genes using whisker-stimulation and resting-state fMRI. SynCAM1 was linked to stronger whisker barrel activation and to greater functional connectivity. However, this was lost if global signal regression was performed. Global signal amplitude was significantly higher in SynCAM1 knockout mice, and amplified by the additional knockout of LRRTM1. We hypothesize this is due to disrupted synaptic connections by SynCAM1 knockout, which are partially protected when LRRTM1 is present.

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