Study finds function of little-understood synapse in brain

WASHINGTON DC: Researchers revealed the function of a little-known junction between cells in the brain, which could have important treatment implications for conditions ranging from multiple sclerosis to Alzheimer's disease to glioma, a type of brain cancer.

The study was published in the journal Nature Neuroscience.

Neuroscientists studied the connection, or synapse, that connects neurons to non-neuronal cells known as oligodendrocyte precursor cells, or OPCs. OPCs can develop into oligodendrocytes, which form a coating surrounding nerves known as myelin. Myelin is the protective coating that surrounds each nerve cell's axon--the threadlike component of the cell that carries electrical information between cells.

According to the study, these synapses play an important function in the production of myelin.

"This is the first investigation of these synapses in live tissue," said senior author Kelly Monk, PhD, professor and co-director of the Vollum Institute at OHSU. "This gives an understanding of the basic, fundamental properties of how these cells work in normal development. In the future, we might look at how they function differently in the context of MS patients."

The fact that these synapses exist at all was the subject of a landmark discovery by OHSU researchers at the Vollum that was published in the journal Nature in May of 2000. Until that point, synapses in the brain had been known only to carry neurotransmitters between neurons, so the discovery of a synapse between neurons and OPCs came as a revelation.

"After two decades, we still didn't know what these synapses do," Monk said.

Scientists tackled the problem by using single-cell imaging of live tissue in zebrafish, whose transparent bodies enable researchers to see the inner workings of their central nervous system in real-time. Using powerful new tools in imaging, pharmacology, and gene editing, researchers were able to use neuron-OPC synapses to predict the timing and location of the formation of myelin.

The findings are likely the tip of the iceberg in terms of understanding the importance of these synapses, said lead author Jiaxing Li, Ph.D., a postdoctoral fellow in Monk's lab.

Oligodendrocyte precursor cells comprise about 5 percent of all cells in the brain, meaning the synapses they form with neurons could be relevant to many disease conditions, including the formation of cancerous tumours.

Li noted that previous studies have suggested a role for OPCs in a range of neurodegenerative conditions, including demyelinating disorders such as MS, neurodegenerative diseases such as Alzheimer's, and even psychiatric disorders like schizophrenia.

By demonstrating the basic function of the synapse between neurons and OPCs, Li said the study may lead to new methods of regulating OPC function to alter disease progression

For example, these synapses could be the key to promoting remyelination in conditions such as MS, where myelin has been degraded. In MS, this degradation can slow or block the electric signals required for people to see, move their muscles, feel sensations, and think.

"There may be a way to intervene so that you can increase the myelin sheath," he said.

Monk said the discovery may be most immediately relevant to cancer.

"In glioma, these synapses are hijacked to drive tumour progression," she said. "It may be possible to modulate the synaptic input involved in tumour formation while still allowing for normal synaptic signalling."

Even though these precursor cells comprise roughly 5 percent of all human brain cells, only a fraction go on to form oligodendrocytes.

"It's becoming pretty clear that these OPCs have other functions aside from forming oligodendrocytes,"Monk said.

"From an evolutionary perspective, it doesn't make sense to have so many of these precursor cells in your brain if they're not doing something."

Their synaptic connection to neurons therefore likely plays a fundamental role in the brain and is worthy of future exploration, she said.