Investigating neuron-OPC synapses in live tissue

Neuroscientists from Oregon Health & Science University (OHSU) have revealed the function of a synapse connecting neurons to oligodendrocyte precursor cells (OPCs). This could have significant implications for conditions such as multiple sclerosis (MS), Alzheimer’s disease (AD), and glioma.

These synapses were a landmark discovery by OHSU researchers at the Vollum, published in Nature in May of 2000. Previously to that, synapses in the brain had been known only to carry neurotransmitters between neurons.

OPCs can differentiate into oligodendrocytes, which produce a myelin, the protective sheath covering each nerve cell’s axon. It has been found that these synapses have a key role in producing myelin.

Dr Kelly Monk, professor and co-director of the Vollum Institute at OHSU, said of the new study: “This is the first investigation of these synapses in live tissue…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.”

Single-cell imaging

To explore the function of neuron-OPC synapses, single-cell imaging of live tissue in zebrafish was used, whose transparent bodies enabled researchers to see the inner workings of their central nervous system (CNS) in real time. Then, utilising tools in imaging, pharmacology and gene editing, the researchers used neuron-OPC synapses to predict the timing and location of the formation of myelin.

Oligodendrocyte precursor cells comprise around five percent of all cells in the brain, which means that the synapses they form with neurons could be relevant to many disease conditions, including the formation of cancerous tumours. However, only a fraction goes on to form oligodendrocytes.

Dr Monk commented: “It’s becoming pretty clear that these OPCs have other functions aside from forming oligodendrocytes…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.” Therefore, their synaptic connection to neurons likely plays an essential role in the brain and is worthy of future exploration.

Dr Jiaxing Li noted that previous studies have suggested a role for OPCs in neurodegenerative conditions like demyelinating disorders such as MS and even psychiatric disorders like schizophrenia. The new study, by demonstrating the basic function of the synapse between neurons and OPCs, could result in new methods of regulating OPC function to alter disease progression. For example, these synapses could be the key to promoting remyelination in conditions such MS, where myelin has been degraded.

Cancer

The discovery may be most immediately relevant to cancer. Dr Monk explained: “In glioma, these synapses are hijacked to drive tumour progression…It may be possible to modulate the synaptic input involved in tumour formation, while still allowing for normal synaptic signalling.”

The study was published in Nature Neuroscience.