Plasticity beyond the synapse: Action potentials and myelination in activity-dependent plasticity and development
Dr. R. Douglas Fields will give a lecture on his current research. Chief of Section in Nervous Development and Plasticity at the National Institute of Child Health and Human Development, Editor-in-Chief of Neuron Glia, Biology, and author of the books Beyond the Synapse and The Other Brain. Abstract: Nervous system development and plasticity are regulated by functional activity during fetal development and by environmental experience in postnatal life. The synapse has always been the focus of research on learning and activity-dependent development, but most cells in the brain are not coupled by synapses, yet they are influenced by electrical activity in neural circuits. Activity-dependent communication outside synapses has broad biological implications, particularly in communication between neurons and glia, but the mechanisms and consequences are far less understood. Our research shows that myelination can be regulated by impulse activity in axons through several different axon-glial signaling mechanisms, including non-vesicular and vesicular release of neurotransmitter from axons. Submicroscopic swelling of axons during excitation releases the neurotransmitter ATP through volume-regulated anion channels. ATP and adenosine increase myelination by promoting development of oligodendrocytes in different ways. Vesicular release of glutamate along axons activates glutamate receptors on oligodendrocytes and stimulates the initial events in myelin formation. This includes the formation of cholesterol-rich signaling domains between oligodendrocytes and axons and stimulating the local translation of myelin basic protein from mRNA in oligodendrocyte cell processes. Thus, electrically active axons would be preferentially myelinated. Since the myelin sheath on axons can increase conduction velocity by at least 50 times, activity-dependent regulation of myelination could contribute to nervous system development and plasticity by modulating the speed and synchrony of impulse conduction through neural circuits. Our results provide possible cellular and molecular mechanisms for changes in white matter seen in human brain imaging in association with environmental experience and learning.