Genetic Variation in CNS Myelination and Functional Brain Connectivity in Recombinant Inbred Mice
Open Access
- 17 September 2020
- Vol. 9 (9), 2119
- https://doi.org/10.3390/cells9092119
Abstract
Myelination greatly increases the speed of action potential propagation of neurons, thereby enhancing the efficacy of inter-neuronal communication and hence, potentially, optimizing the brain’s signal processing capability. The impact of genetic variation on the extent of axonal myelination and its consequences for brain functioning remain to be determined. Here we investigated this question using a genetic reference panel (GRP) of mouse BXD recombinant inbred (RI) strains, which partly model genetic diversity as observed in human populations, and which show substantial genetic differences in a variety of behaviors, including learning, memory and anxiety. We found coherent differences in the expression of myelin genes in brain tissue of RI strains of the BXD panel, with the largest differences in the hippocampus. The parental C57BL/6J (C57) and DBA/2J (DBA) strains were on opposite ends of the expression spectrum, with C57 showing higher myelin transcript expression compared with DBA. Our experiments showed accompanying differences between C57 and DBA in myelin protein composition, total myelin content, and white matter conduction velocity. Finally, the hippocampal myelin gene expression of the BXD strains correlated significantly with behavioral traits involving anxiety and/or activity. Taken together, our data indicate that genetic variation in myelin gene expression translates to differences observed in myelination, axonal conduction speed, and possibly in anxiety/activity related behaviors.This publication has 68 references indexed in Scilit:
- Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of TraitsCell, 2012
- Insights into the regulation of protein abundance from proteomic and transcriptomic analysesNature Reviews Genetics, 2012
- Comparison of the performance of DBA/2 and C57BL/6 mice in transitive inference and foreground and background contextual fear conditioning.Behavioral Neuroscience, 2012
- Genetic Dissection of Behavioral Flexibility: Reversal Learning in MiceBiological Psychiatry, 2011
- Distal axonopathy with structural persistence in glaucomatous neurodegenerationProceedings of the National Academy of Sciences of the United States of America, 2010
- SCAP is required for timely and proper myelin membrane synthesisProceedings of the National Academy of Sciences of the United States of America, 2009
- Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS MyelinationCell, 2009
- Strain Specific Synaptic Modifications on Ventral Tegmental Area Dopamine Neurons After Ethanol ExposureBiological Psychiatry, 2009
- White matter in learning, cognition and psychiatric disordersTrends in Neurosciences, 2008
- Myelin transcription factor 1 (Myt1) expression in demyelinated lesions of rodent and human CNSGlia, 2007