Your brain contains billions of inter-connected cells, or neurons, which work by sending electrical signals from one to another. These electrical events are vital in adult brains, but they’re also a feature of the young developing nervous system. What’s more, changing the electrical activity that occurs in the developing brain can have dramatic effects on a neuron’s identity, its position, its shape, and its connections with other cells. In other words, electrical signals are crucial for normal brain development.
Our lab is interested in just how electrical activity influences the development of the brain, with special emphasis on two inter-connected processes:
1) The main focus of our work is a part of the brain called the olfactory bulb.
This is the first brain region to receive information about smells from the nose. It processes that information and then passes it onto other parts of the olfactory system where our perceptions of smell and flavour are created. We’re interested in the olfactory bulb because we’re fascinated by how our sense of smell works, and also because it has some unusual properties which make it a great model system to study basic processes of maturation in the brain.
The olfactory bulb is an especially plastic part of the brain, meaning that it changes a lot depending on its recent history of activity. Even by the standards of the bulb, one specialised type of neuron found in its circuits is especially plastic. Dopaminergic cells of the olfactory bulb are a local population of neurons that, by releasing the neurotransmitter dopamine (hence the name), regulate the processing of olfactory information at its very earliest stages. They are known to change in many ways in response to particular smell experiences, not the least of which involves completely replacing themselves in a process known as adult neurogenesis. Whereas most of the neurons in your brain right now were born before you were, and won’t be replaced if you lose them, certain types of cell in your olfactory bulb – including some of the dopaminergic ones – were born very recently, and might be replaced in a couple of months by freshly-born neurons generated through adult neurogenesis.
We think this is amazing, and our research aims to find out not only how individual dopaminergic cells in the olfactory bulb can change themselves over time, but also how newly-generated dopaminergic neurons can squeeze their way into a network of interconnected neurons that are already established and doing their smell-processing work, without messing that network up.
2) Our second area of interest involves a highly specialised part of the neuron.
Brain cells have a very distinct shape that you’re probably familiar with, but what you might not know is that different parts of a neuron are designed to carry out certain specific tasks in processing electrical signals. In simple terms, the large spherical bulge in the middle of the cell is known as the cell body, or soma. It contains all of the ‘housekeeping’ machinery needed to keep the cell healthy and functioning. Sticking out from the soma and spreading to look something like the branches of a tree are processes called dendrites, which act primarily as the cell’s input-receiving area – they listen in to signals being sent to them from other neurons. Once they arrive in the dendrites, these signals spread, going further the stronger they are. If they are strong enough, they might spread into the axon, which is long, thin, and extends from the soma. This is the output structure of the neuron, using input coming in from the dendrites and soma to generate big electrical signals called action potentials, which then travel to the end of the axon (the axon terminals) and there start to influence the activity of other brain cells.
We’re interested in a particular ‘hotspot’ near the start of the axon, called the axon initial segment, or AIS. This is the part of a neuron which is most sensitive to electrical activity, which means that it is the site where action potential signals invariably start. Despite this crucial role in kick-starting communication between brain cells, scientists actually know surprisingly little about the AIS, and even less about how it develops and changes over time. Our lab has published evidence that the AIS can change a lot in response to alterations in the ongoing electrical activity of brain cells – in fact, it’s one of the sites of plasticity that we’re so interested in studying in olfactory bulb dopaminergic neurons. We know that alterations at the AIS are associated with changes in the way neurons produce action potentials, as you might expect from any mechanism that meddles with a brain cell’s major output trigger zone. What we don’t know yet is exactly how neurons bring about changes at their AIS, and more importantly how they co-ordinate alterations at the AIS with other plastic changes in their structure and function happening at the same time in response to the same stimuli.
These are basic scientific questions, but they could have serious clinical relevance. Understanding plasticity at the AIS might help a little in the search for treatments for brain disorders where neurons produce action potentials too readily, such as epilepsy. By studying plasticity in the olfactory bulb, we also hope to stimulate research into novel treatments for smell disorders – a serious set of conditions with huge impact on people’s health and quality of life, and which affect a surprisingly large proportion of the population. And finally, by investigating the mechanisms and consequences of adult neurogenesis, we hope to one day inform treatment strategies trying to replace human cells lost through injury or disease. If we’re trying to replace old cells with new cells, why not take a few hints from the way the brain does it all on its own?