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Leverhulme Trust grant awarded to Matt Grubb


Congratulations to Matt Grubb for, in collaboration with Professor Jon Mill at Exeter University, having been awarded a three-year grant by Leverhulme Trust for their proposal titled “Linking functional and epigenetic plasticity at the single-neuron level

Your everyday experiences, such as reading the paper, enjoying a meal or even catching a cold, change your brain to allow learning and adaptation in a constantly-changing world. These changes are collectively known as ‘plasticity’, and occur via a huge array of mechanisms ranging from alterations in the structure of individual molecules through to changes in the strength of connections between entire brain regions. However, while we have some understanding of the way in which experience can alter individual features of the brain, we know much less about how these separate forms of plasticity interact. For example, changes in sensory experience can alter both the electrical properties of brain cells – this is known as ‘functional’ plasticity – and the chemical structure of their DNA – this is known as ‘genomic’ plasticity – but the links, influences and integration between these two forms of plasticity remain almost entirely unexplored. The aim of this research project is to answer this fundamental question: how does the brain combine functional and genomic plasticity simultaneously in individual cells?

Studying multiple forms of plasticity in single brain cells, or ‘neurons’, is crucial because of those cells’ sheer diversity. There are not only a multitude of different subclasses of neurons within each region of the nervous system, but just as many variations within each of these subclasses. Such heterogeneity makes it difficult to detect subtle alterations brought about by specific experiences, and most likely obscures a wealth of relationships that exist between different forms of plasticity at the single-cell level. To truly understand the interactions between different types of plasticity – and in so doing, get a clearer idea of how our brains are shaped by the lives we lead – therefore requires us to study multiple forms of plasticity in individual neurons.

The researchers‘ goal is therefore to interrogate, simultaneously in the very same brain cells, two vital but very different forms of plasticity. They will do this in a specific cell population called dopaminergic neurons, which are located in an area of the mouse brain – the olfactory bulb – that first processes information about the sense of smell. It is already known that these cells can be very plastic, and can be readily manipulated via simple alterations of olfactory experience. They aim to uncover both predicted and entirely unexpected relationships between gene regulation and electrical function within individual brain cells, which will lead to a better understanding of how our experiences make us who we are.