Analyzing learning-evoked myelination

Abstract

Oligodendrocytes are important glial cells in the central nervous system, where they generate myelin sheath that coats the axons of nerve cells, resulting in faster neurotransmission and synchronisation of neuronal inputs. Improper myelination can lead to nerve death and damage to myelin is a large factor in numerous diseases, such as Multiple Sclerosis. Recent studies have found that learning acquisition, such as learning a new motor skill, increases myelination and oligodendrocyte generation. With this knowledge at hand, we performed an experiment on cognitive learning, to gain further information on the mechanisms of myelination. A trial-unique nonmatching-to-location task was performed on pdgfra-CreER:tau-mGFP transgenic mice, to assess oligodendrocyte differentiation. The task has been shown to rely on working memory and pattern separation in rodents. Tissue staining for GFP, Olig2, and EdU was performed for quantification of cells in the dorsal hippocampus [dHP] and the medial prefrontal cortex [mPFC]. Number of GFP/Olig2 positive cells revealed that cognitive learning increases oligodendrocyte differentiation, and number of GFP/Olig2/EdU positive cells show that oligodendrocyte proliferation takes place mainly in the beginning of the training period. Stereotaxic injections were made to the dHP and mPFC to allow for viral tracings of nerve fibers and whether they are being myelinated. We found an increased myelination of axonal tracts in the mPFC in response to learning. Results also show an increased internodal length in the dHP after learning, and a higher number of internodes in the mPFC. We compared different oligodendrocyte phenotype and found that a myelinating phenotype has a more complex structure and extends its processes further from the soma, than does a non-myelinating phenotype. We employed triple transgenic mice with a conditional knockout of myelin regulatory factor [MyRF] to take part in the trial-unique nonmatching-to-location task. Results show that without MyRF, the mice have difficulties learning and lack myelinating oligodendrocytes.