Unique Changes On Functional Magnetic Resonance Imaging Maps Following D2 Receptor and Cholinergic Specific Knock-Out of TorsinA
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WE-IePD-TRACK 4-7 (Wednesday, 7/28/2021) 3:00 PM - 3:30 PM [Eastern Time (GMT-4)]
Purpose: The objective of this study was to compare how loss of torsinA function in D2R and cholinergic cells within the striatum impairs motor deficits, sensory evoked blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), sensory-evoked functional connectivity, and tissue microstructure using in vivo high field magnetic resonance imaging.
Methods: We used two genetic mouse models characterized by conditional knock-out of torsinA in either D2R-expressing striatal neurons or striatal cholinergic interneurons for motor behavior assessment (accelerated Rotarod and Beam-walking). Furthermore, we acquired in vivo sensory-evoked fMRI and in vivo diffusion magnetic resonance imaging (dMRI) to assess tissue microstructural changes across the whole brain, as this technique has shown promise in studying neurodegeneration.
Results: The findings demonstrate that knock-out of torsinA from d2R-expressing striatal cells and striatal cholinergic interneurons have profound effects on sensory-evoked BOLD fMRI, sensory-evoked functional connectivity, and motor deficits: (1) The within-group effects on the β-coefficients. In all groups, BOLD activation was significantly increased within the sensorimotor cortex, cingulate, retrosplenial area, parietal cortex, striatum, globus pallidus, thalamus, cerebellar cortex, and brainstem. (2) The seed-based correlation of functional connectivity with the striatum during sensory-evoked fMRI. Dyt1 d2KO and Ch2KO mice showed abnormal functional connectivity in sensory-evoked functional MRI compared to their control littermates. (3) Correlation between fMRI and behavior deficits, with the region of significance between-group difference found for the sensory-evoked BOLD activation and sensory-evoked functional connectivity.
Conclusion: The study determines how systemic level changes in brain function, connectivity, and microstructure are influenced by knock-out of torsinA using high field 11T fMRI and dMRI. The findings demonstrate that knock-out of torsinA from d2R-expressing striatal cells has profound effects on sensory-evoked BOLD fMRI, sensory-evoked functional connectivity, which have high correlation with the subjects' motor deficits.
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