Faculty, Staff and Student Publications
Publication Date
8-1-2024
Journal
Nature Neuroscience
Abstract
Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects in activity-dependent oligodendrogenesis and harbor focal OPC hyperdensities with disrupted homeostatic OPC territorial boundaries. These OPC hyperdensities develop in a cell-intrinsic Nf1 mutation-specific manner due to differential PI3K/AKT activation. OPC-specific Nf1 loss impairs oligodendroglial differentiation and abrogates the normal oligodendroglial response to neuronal activity, leading to impaired motor learning performance. Collectively, these findings show that Nf1 mutation delays oligodendroglial development and disrupts activity-dependent OPC function essential for normal motor learning in mice.
Keywords
Animals, Female, Male, Mice, Cell Differentiation, Learning, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Mutation, Neurofibromin 1, Neuronal Plasticity, Oligodendroglia
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
Data Availability Statement
PMID: 38816530