Lyons, zebrafish and myelin repair
Hi David, we hear you’ve been to Spain recently?
Yes, the MS Society recently supported my colleague Dr. Ragnhildur Thora Karadottir and I to organise a symposium on myelin at a large international conference in Spain. Over 1,000 researchers got together to discuss different areas of neurological research. Our session focussed on how brain activity regulates myelination (the process of making myelin) and remyelination (myelin repair).
I spoke about our recently published work which looked at how the activity of neurons in the brain regulates myelin production: basically hyperactive neurons are myelinated more. We’ve been looking at whether all neurons behave like this by following individual neurons in zebrafish over time.
We have found some neurons regulate their own myelination and some don’t. It depends on where a neuron is in a particular circuit, giving us further insight into the importance of networks of neurons in the brain.
We tend to think all neurons need loads of myelin, to send signals fast – but different neurons have different roles, so it’s not just about the ‘need for speed’.
Can you give us any inside gossip from the symposium?
There were lots of great talks and I can give you some insight on the other research discussed in our session on brain activity and myelin.
Lighting up neurons
Michelle Monje, from Stanford University, spoke about an amazing technique called ‘optogenetics’. Researchers can put proteins into neurons to make them react to light, which means you can regulate their activity by shining light on them.
Michelle and her team found after they’d activated neurons in a mouse brain, there were loads more myelin-making cells (oligodendrocytes) in that area. There was also more myelination, suggesting the amount of myelin made relates to neuron activity.
Stan Mitew from the University of Melbourne spoke about a technique called chemogenetics which uses chemicals instead of using light to regulate neuron activity. Stan and his colleagues put particular receptors (proteins activated by specific chemicals) into neurons, and then added the matching chemical to activate the neurons containing the receptors.
The receptors were fluorescent green, so they could ask a very specific question – is it only the activated neurons that are more likely to be myelinated, or do they also cause the (less active) neurons around them to be myelinated? They showed a more active neuron had thicker myelin and was more likely to be myelinated than its neighbours.
Whilst similar, chemogenetics is not as precise as optogenetics – it causes more general hyperactivity. This has its upsides though: neurons can’t tolerate being activated for a long time by optogenetics, they just give up. The chemical regulation is better tolerated, so more long-term studies can be done on the cells.
Thora Karadottir spoke about how neuron activity plays an important role in the formation of myelin-making oligodendrocytes. Her group have also investigated what kind of molecules might be involved in this process. This will be important for trying to produce the same behaviour during myelin repair in MS, which often fails. Gaining insights into how brain activity regulates myelination offers great hope.