Oligodendrocytes are glial cells that regulate conduction velocity (CV) by synthesizing myelin and wrapping it around axons. Myelinated axons make up the white matter of the brain, which connects distant cortical regions and therefore plays an important role in information processing.Recent fMRI studies have shown that the white matter shows increased signals in response to learning, indicating white matter plasticity in the adult brain.
Myelin proteolipid protein 1 (PLP1) is a major component of myelin and is involved in myelin homeostasis. Two-month-old PLP1-overexpressing (PLP-tg) mice have mild morphological abnormalities in the nodes of Ranvier, which lead to decreased axonal CV and abnormal anxiety-related behaviors.
To determine whether impaired myelin homeostasis can affect learning processes, we evaluated the behavioral performance of PLP-tg mice using a lever-pulling task (Hira, et al., J. Neurosci.33, 2013). PLP-tg mice showed poor performance compared to wild-type (WT) animals. WT mice showed a learning-dependent change in myelin-related protein mRNA expression, which was absent in PLP-tg mice, suggesting that PLP-tg mice lack white matter plasticity during motor learning. To understand the neural basis for this impaired learning performance, we injected an adeno-associated virus coding a green fluorescent protein-based calcium calmodulin probe into layer 2/3 of the motor cortex. This technique allowed us to visualize the firing pattern of neurons. The firing rate of neurons under anesthesia did not differ between WT and PLP-tg mice. We then examined whether the neural activity pattern during the lever-pulling task differed between WT and PLP-tg mice.