A new mechanism of nervous system plasticity: activity-dependent myelination

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Abstract

The synapse is the focus of experimental research and theory on the cellular mechanisms of nervous system plasticity and learning, but recent research is expanding the consideration of plasticity into new mechanisms beyond the synapse, notably including the possibility that conduction velocity could be modifiable through changes in myelin to optimize the timing of information transmission through neural circuits. This concept emerges from a confluence of brain imaging that reveals changes in white matter in the human brain during learning, together with cellular studies showing that the process of myelination can be influenced by action potential firing in axons. This Opinion article summarizes the new research on activity-dependent myelination, explores the possible implications of these studies and outlines the potential for new research.

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White matter is the brain region underlying the gray matter cortex, composed of neuronal fibers coated with electrical insulation called myelin. Previously of interest in demyelinating diseases such as multiple sclerosis, myelin is attracting new interest as an unexpected contributor to a wide range of psychiatric disorders, including depression and schizophrenia. This is stimulating research into myelin involvement in normal cognitive function, learning and IQ. Myelination continues for decades in the human brain; it is modifiable by experience, and it affects information processing by regulating the velocity and synchrony of impulse conduction between distant cortical regions. Cell-culture studies have identified molecular mechanisms regulating myelination by electrical activity, and myelin also limits the critical period for learning through inhibitory proteins that suppress axon sprouting and synaptogenesis.

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Magnetic resonance imaging (MRI) provides accurate anatomical brain images without the use of ionizing radiation, allowing longitudinal studies of brain morphometry during adolescent development. Results from an ongoing brain imaging project being conducted at the Child Psychiatry Branch of the National Institute of Mental Health indicate dynamic changes in brain anatomy throughout adolescence. White matter increases in a roughly linear pattern, with minor differences in slope in the four major lobes (frontal, parietal, temporal, occipital). Cortical gray matter follows an inverted U-shape developmental course with greater regional variation than white matter. For instance, frontal gray matter volume peaks at about age 11.0 years in girls and 12.1 years in boys, whereas temporal gray matter volume peaks at about age at 16.7 years in girls and 16.2 years in boys. The dorsal lateral prefrontal cortex, important for controlling impulses, is among the latest brain regions to mature without reaching adult dimensions until the early 20s. The details of the relationships between anatomical changes and behavioral changes, and the forces that influence brain development, have not been well established and remain a prominent goal of ongoing investigations.