Case study: Researcher W

Research: understanding how the brain develops, both normally and in neurological diseases.

Animals used: tadpoles

Researcher W (prefers to remain anonymous): ‘My research group is trying to understand how a nerve cell in the brain forms connections with other nerve cells in the brain, early in life. This process often goes wrong in early development. Many disorders, such as mental retardation, schizophrenia, and epilepsy, involve errors in how nerve cells connect to one another in the early development of the brain.

‘My work aims to find out what the normal processes are and, from that, how exactly they can go wrong. That is of direct use to clinical colleagues who are looking at how to prevent or treat these disorders.

‘In my work I use the tadpoles of a type of frog called Xenopus. Tadpoles can give us a lot of information about the developing brain, for two main reasons. One, we get access to animals very early in development, because the embryos develop outside the mother’s body. We can therefore study brain cells at a very early stage in a way we couldn’t in a mammal. Two, tadpoles are translucent, allowing to look inside the brain tissue of a live animal non-invasively. The ultimate aim of the experimental biologist is to examine phenomena in the intact tissue, where you have all physiological aspects maintained and you can explore the effects of the environment on the animal.

‘A large proportion of what we do uses microscopes to look at behaviour of brain cells in the tadpole. The fact that it’s translucent allows us to do this in a very non-invasive way. By fluorescently marking a particular nerve cell in a tadpole’s brain and then putting the tadpole under the microscope each day, we can generate a time lapse picture of a single nerve cell developing in a living brain. We’re interested in seeing how the structure of the nerve cell is established – as structure is key to how it forms connections – and how “daughter” nerve cells are born from “mother” cells.

‘We also use microelectrodes – tiny brain probes – to record what is happening in a single nerve cell of the tadpole’s brain during visual stimulation. We anaesthetise the tadpole, put it under a microscope, and place these electrodes onto a single nerve cell in its brain. We then present visual stimuli to the animal and record the responses of the nerve cell. Tadpoles can see and respond to very simple visual stimuli like shadows in order to avoid predators. And the responses of the tadpole brain cells involve the same chemical and electrical signals that operate in our brain cells. Therefore, amazing as it may sound, finding out how a nerve cell in a tadpole’s brain responds to a sensory stimuli gives us information that is very relevant to how brain cells develop in a human baby.

‘Our work has characterised some of the signals between nerve cells which change the strength and type of connections between them. At the clinical end of things, the mechanisms we’re trying to understand, and are understanding more, relate to how nerve cells control their own electrical excitability.

‘Epilepsy is a situation where this control is lost. Epilepsy is a tendency to have recurrent seizures or fits, which are caused by a sudden burst of excess electrical activity in the brain. At the moment there is no cure. It affects around one in every 280 children. The mechanisms my colleagues and I are characterising in normal development speak directly to those that go wrong in epilepsy.

‘The main benefit of the Biomedical Sciences Building for our research group is that there is a pool of expertise in terms of technical support. When the building was completed, technicians formerly in different facilities all moved to one place and there is now a concentration of expertise. There are animal technicians in the building who generate the tadpole embryos for us, which frees up researchers’ time to study the results.’