2020
DOI: 10.1101/2020.03.31.016089
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Brain-wide structural and functional disruption in mice with oligodendrocyte specificNf1deletion is rescued by inhibition of NOS

Abstract: Neurofibromin gene (NF1) mutation causes Neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, Nf1 loss in adult oligodendrocyte causes myelin decompaction, and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology. Whether oligodendrocyte pathology is sufficient to affect brainwide structure and account for NF1 imaging findings is unknown. Here,… Show more

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Cited by 3 publications
(7 citation statements)
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“…Future studies can use the individual functional connectome to predict the effect of causal control similar to the way human resting-state fMRI is used to predict individual task fMRI activation pattern 9 , linking the different levels of organization and uncovering sources of individual variation. In addition, rodent models of disease are commonly studied using fcMRI 21,22,29,65 , which allows direct translation to humans 20,28 , as well as studying the relations between functional connectivity and behavior [23][24][25][26] . Such studies can utilize the approach presented here to follow the trajectory of individual animals during development, aging or after treatment, as well as CPM, which provides a data-driven alternative for fcMRI-based behavioral prediction 35 , rather than the hypothesis-driven approach that examines the behavioral correlations of specific functional connections.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Future studies can use the individual functional connectome to predict the effect of causal control similar to the way human resting-state fMRI is used to predict individual task fMRI activation pattern 9 , linking the different levels of organization and uncovering sources of individual variation. In addition, rodent models of disease are commonly studied using fcMRI 21,22,29,65 , which allows direct translation to humans 20,28 , as well as studying the relations between functional connectivity and behavior [23][24][25][26] . Such studies can utilize the approach presented here to follow the trajectory of individual animals during development, aging or after treatment, as well as CPM, which provides a data-driven alternative for fcMRI-based behavioral prediction 35 , rather than the hypothesis-driven approach that examines the behavioral correlations of specific functional connections.…”
Section: Discussionmentioning
confidence: 99%
“…Since this experimental design is hard to achieve in anesthetized animals, such studies can benefit from awake mouse imaging. We have previously established fcMRI experiments in awake head-fixed mice [27][28][29] and used repeatedmeasurement designs to link individual differences in structural and functional connectivity 30 . However, a detailed analysis of individual variability of functional connectivity in the mouse brain and its relevance to behavior has heretofore not been demonstrated.…”
mentioning
confidence: 99%
“…Mice of each genotype (n = 13 per group) underwent multiple awake head-fixed fcMRI sessions, as previously described 14,17,40,41 . Imaging of animals in the awake state may be impacted by stress and in group comparisons, genotype-specific response to stress may be raised as a concern.…”
Section: Resting-state Fmri Acquisition and Preprocessingmentioning
confidence: 99%
“…Raw data were preprocessed as previously described 14,17,40,41 , including removal of the first two volumes for T1-equilibration effects, compensation of slice dependent time shifts, rigid body correction for head motion, registration to a downsampled version of the AMBC atlas 36,37 , and intensity normalization. Data scrubbing was applied as previously described 14,44 with exclusion criteria of 50 μm framewise displacement and derivative root-mean-square variance over voxels (DVARS) of 150% inter-quartile range (IQR) above the 75th percentile and exclusion of one additional frame after the detected motion.…”
Section: Resting-state Fmri Acquisition and Preprocessingmentioning
confidence: 99%
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