Which signals regulate myelination?

How might neural activity affect myelination?

How do activity-driven changes to myelination affect brain function? 

How does demyelination affect oligodendrocytes and neurons? 

How can we find new treatments for demyelinating diseases?

Many signals regulate myelination and myelinated axon formation, health and function, some of which are currently being investigated by Jenea Bin. Recently completed projects in the lab include a study of oligodendrocyte neurofascin (Klingseisen et al., 2019), of NKCC1 function in the peripheral nervous system (Kegel et al., 2020), of oligodendrocyte calcium signalling (Baraban et al., 2018), and of endothelin signalling (Swire et al., 2019). Philipp Braaker is looking into the interaction between glutamate and calcium signalling, and their role in the myelination of the spinal cord.

We know that axons make synaptic connections with oligodendrocytes, essentially communicating with them as if they were other neurons. This may be one way in which the activity of a neural circuit could modify myelin, so that circuit function could be tuned to behaviour. Previous research in our lab showed that oligodendrocytes adjust their patterns of myelination depending on the activity of axons in their vicinity (see Mensch et al., 2015; Koudelka et al., 2016; Almeida et al., 2018), and that they only have a short window of time in which to do so.

Rafael Almeida is currently investigating how axonal vesicle release triggered by neuronal activity affects oligodendrocytes and the formation, growth, and maintenance of their myelin sheaths.

Myelination occurs in a wider context of neural networks and brain circuits. We are investigating how changing the pattern of myelination affects the fundamental nature of brain function. Our recently graduated PhD student, Megan Madden, studied how the behaviour of larval zebrafish was affected by altered myelin patterning.

Daumantė Šuminaitė, our electrophysiology wizard,  is investigating the functional properties of individual myelinated neurons, how they conduct electrical impulses, and how this translates to synaptic communications.

Myelin is a key player in nervous system function. As such, it is crucial to understand how myelin develops and interacts with other cells in the brain. However, the overarching goal of our research is to improve the prognosis of debilitating neurodegenerative diseases. Multiple sclerosis (MS) is a major demyelinating disorder of the brain, in which our immune system aberrantly attacks myelin. Due to the loss of myelin, neuronal function is impaired, and the neurons often degenerate. Currently, we are unable to prevent neurodegeneration in MS, but we know that remyelination can occur.

To study how the nervous system is affected after demyelination, and in the hope of finding new treatments, we created a zebrafish model of demyelination. Sarah Neely is studying the oligodendrocytes which survive demyelination, and how well they fare (Neely et al., 2020). Donia Arafa also want to understand how this model affects neuronal function, since we still don’t know what causes the neurons to degenerate following demyelination.

Using the demyelination model, Katy Marshall-Phelps and Marcus Keatinge are undertaking an automated screen to test a library of drugs with the potential to boost remyelination. Such projects are possible thanks to the work of Jason Early, our resident microscope whisperer (Early et al., 2018).