Summary: Researchers say astrocytes play a vital role in information processing by altering neurotransmission speeds and changing the thickness of myelin.
The transmission speed of neurons fluctuates in the brain to achieve an optimal flow of information required for day-to-day activities, according to a National Institutes of Health study. The results, appearing in PNAS, suggest that brain cells called astrocytes alter the transmission speed of neurons by changing the thickness of myelin, an insulation material, and the width of gaps in myelin called nodes of Ranvier, which amplify signals.
“Scientists used to think that myelin could not be thinned except when destroyed in demyelinating diseases, such as multiple sclerosis,” said R. Douglas Fields, Ph.D., senior author and chief of the Section on Nervous System Development and Plasticity at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Our study suggests that under normal conditions, the myelin sheath and structure of the nodes of Ranvier are dynamic, even in adults.”
The brain is composed of neurons, which have extensions called axons that can stretch for long distances. Axons are wrapped by layers of myelin, which serve as insulation to increase the speed of signals relayed by neurons. Gaps between segments of myelin are called nodes of Ranvier, and the number and width of these gaps can also regulate transmission speed.
“Myelin can be located far from the neuron’s synapse, where signals originate,” said NICHD’s Dipankar Dutta, Ph.D., the lead author of the study. “We wanted to understand how myelin, and the cells that regulate it, help synchronize signals that come from different areas of the brain.”
The researchers focused their attention on perinodal astrocytes, which frequently touch nodes of Ranvier throughout the brain. In experiments using mice and rats, the researchers found that these astrocytes regulate adhesion molecules that connect myelin to axons. When these molecules are cut by the enzyme thrombin, myelin detaches from the axon, layer by layer.
The researchers blocked the ability of perinodal astrocytes to regulate thrombin and observed thinner myelin sheaths and wider nodes of Ranvier. In turn, these changes reduced the signal speeds of neurons by approximately 15 percent, which was enough to impair reflexes of mice in a vision-based test.
The findings suggest that astrocytes, by regulating signal speeds, play an important role in how the brain processes information. Furthermore, the researchers propose that blocking thrombin may help stabilize myelin. Thrombin inhibitors are already approved by the U.S. Food and Drug Administration for other uses, and the study team is currently testing their idea in a mouse model of multiple sclerosis.
Funding: Funding for the work was provided by NICHD and other NIH components, including the Center for Information Technology, the National Institute of Neurological Disorders and Stroke, and the National Cancer Institute. Additional support was provided by the Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine.
Source: Linda Huynh – NIH/NICHD
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Fields Laboratory, NICHD/NIH.
Original Research: Open access research for “Regulation of myelin structure and conduction velocity by perinodal astrocytes” by Dipankar J. Dutta, Dong Ho Woo, Philip R. Lee, Sinisa Pajevic, Olena Bukalo, William C. Huffman, Hiroaki Wake, Peter J. Basser, Shahriar SheikhBahaei, Vanja Lazarevic, Jeffrey C. Smith, and R. Douglas Fields in PNAS. Published October 29 2018.
Regulation of myelin structure and conduction velocity by perinodal astrocytes
The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impulse transmission is influenced by the thickness of the myelin sheath and the morphology of electrogenic nodes of Ranvier along axons. Here we show that myelin thickness and nodal gap length are reversibly altered by astrocytes, glial cells that contact nodes of Ranvier. Thrombin-dependent proteolysis of a cell adhesion molecule that attaches myelin to the axon (neurofascin 155) is inhibited by vesicular release of thrombin protease inhibitors from perinodal astrocytes. Transgenic mice expressing a dominant-negative fragment of VAMP2 in astrocytes, to reduce exocytosis by 50%, exhibited detachment of adjacent paranodal loops of myelin from the axon, increased nodal gap length, and thinning of the myelin sheath in the optic nerve. These morphological changes alter the passive cable properties of axons to reduce conduction velocity and spike-time arrival in the CNS in parallel with a decrease in visual acuity. All effects were reversed by the thrombin inhibitor Fondaparinux. Similar results were obtained by viral transfection of tetanus toxin into astrocytes of rat corpus callosum. Previously, it was unknown how the myelin sheath could be thinned and the functions of perinodal astrocytes were not well understood. These findings describe a form of nervous system plasticity in which myelin structure and conduction velocity are adjusted by astrocytes. The thrombin-dependent cleavage of neurofascin 155 may also have relevance to myelin disruption and repair.