Study reveals how gephyrin helps control myelin formation in the brain
Scientists have long known that disruptions in synaptic communication are a central part of the puzzle of neuropsychiatric disorders including autism, schizophrenia and bipolar disorder.
A research team led by Bruce Appel, PhD, professor of pediatrics-developmental biology at the CU Anschutz School of Medicine, wondered why people with these types of disorders often have abnormalities in myelin as well. Myelin is a protective, insulating coating around axons, the nerve fibers that carry signals in the brain and spinal cord.
The study published in Nature Communications showed how oligodendrocytes, which are glial cells in the central nervous system that produce myelin, help fine-tune neural circuits in zebrafish by controlling where myelin forms. "Myelination is not simply a hardwired process. There is a genetic regulation that provides a selectivity and specificity," Appel said.
More specifically, the zebrafishes' oligodendrocytes use the postsynaptic scaffold protein gephyrin to preferentially form myelin around inhibitory axons while simultaneously shortening the length of myelin sheaths they produce.
What did the researchers discover about myelination?
- Axon selection: Gephyrin helps oligodendrocytes preferentially myelinate inhibitory axons.
- Sheath growth: Without gephyrin, myelin sheaths grow longer than normal.
- Neural circuit balance: Changes in myelination may affect the balance between excitatory and inhibitory signaling, although the study did not directly test this effect.
The study also found that in the absence of gephyrin, the oligodendrocytes myelinate the inhibitory axons less frequently and excitatory axons more frequently. Inhibitory and excitatory signaling work together to maintain balanced activity in the brain.
An excitation-inhibition imbalance is a well-researched neurobiological theory of autism spectrum disorder. "Our study raises the possibility that if you myelinate inhibitory axons less frequently and excitatory axons more frequently, that's going to contribute to the hyper-excitation of the excitatory neural circuits," Appel said.
Glossary:
Myelination - The process of forming myelin, an insulating coating around nerve fibers that helps electrical signals travel efficiently.
Oligodendrocytes - Specialized cells in the brain and spinal cord that produce myelin.
Gephyrin - A scaffolding protein that organizes other proteins involved in cell signaling and, as this study shows, helps regulate myelin formation.
Inhibitory axons - Nerve fibers from neurons that help reduce or restrain activity in neural circuits.
Excitatory axons - Nerve fibers from neurons that help increase activity in neural circuits.
GABAergic and glycinergic axons - Axons associated with neurons that use GABA or glycine, two inhibitory neurotransmitters.
Synapse - a junction where one neuron communicates with another cell.
The following Q&A further explains the study findings, including the suggestion that some of the molecular mechanisms involved in synapses may also help regulate myelin formation. The interview has been edited for length and clarity.
