Control of local protein synthesis and initial events in myelination by action potentials

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NICHD	CELLBIO-10

* FARE Award Winner

Authors

• PR Lee
• RD Fields

Abstract

Neural activity stimulates myelin formation, the electrical insulation on nerve fibers, in association with learning and postnatal experience. Oligodendrocytes, the myelinating glia of the CNS, are morphologically complex cells that are capable of myelinating multiple axons independently from many different cellular extensions and induce rapid conduction of electrical impulses in the vertebrate brain. We have shown that oligodendrocytes, the myelinating glia of the CNS, exhibit elevated Ca2+ responses in their fine processes and cell soma, in response to action-potential (AP) firing in axons. These Ca2+ responses in oligodendrocytes exhibit differential kinetics, reflective of a specific intracellular response to electrical-activity evoked neurotransmitter release from axons. We have demonstrated that elevated Ca2+ responses in oligodendrocyte processes promotes the turnover of cholesterol rich domains as visualized by a pH sensitive GFP fused with transferrin receptor. We have visualized myelin basic protein (MBP) local translation using a photo-convertible GFP fused to the 3'UTR of MBP. We also demonstrate that local translation of MBP mRNA in oligodendrocyte processes is initialized myelin formation at the site of connection between oligodendrocytes and axons. These findings provide new insight into how myelination, and thus conduction velocity and function of neural circuits, can be regulated by nervous system activity.

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