How do the spatiotemporal dynamics of insulin signalling control neuron size and function?

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The brain is staggeringly complex. It is made of billions of neurons that extend tree-like branches and connect with 1000s of partners. These complex networks of connections are essential for the correct functioning of the nervous system, they need to be stable enough to process and store information (memories) but also dynamic to respond and change from experience (learning). How brains are built is still one of the biggest questions in biology.How neuron growth is controlled and how a particular neuron 'knows' what size to reach is intriguing. The growth of a neurons branches determines the potential partners it can make connections with and also sets in place some electrical properties which dictate how it fires. Some neurons have small trees with branches that don't spread very far and process local information within brain circuits whereas others send information long distances, like the neurons that run from your spine down to the muscles that control your big toe. We would like to understand what allows the small neurons to be small and big neurons to be big. To gain new insights into neuron size control we are using the powerful genetics and complex nervous system of fruit flies (Drosophila). Our preliminary data show a pathway called the Insulin/Insulin-like Growth factor signalling and Target of Rapamycin is required to generate appropriately sized trees. We have tested many different neurons in flies and these experiments point toward insulin signalling being a global player in the nervous system. Each neuron appears to have a distinct tuning that sets what size it should be. How this is controlled and what part it plays shaping neurons will be investigated.We are able to watch neurons growing live during metamorphosis using fluorescent proteins from jellyfish and high-magnification microscopes. We are now able to do many new experiments with specially engineered flies where the gene have peen precisely edited. This will allow us to get fine measurements of the components in the pathways we are interested in.Our hope is that we will find something important and universal about nervous system design principles. Alongside this we know that developmental wiring defects can have very serious consequences and manifest as disorders such as autism, schizophrenia and epilepsy. All of which have a massive impact on society. The genes in the pathways above have been found in patients with autism and epilepsy. For both fundamental and medical science we need to know more about how neurons grow and set their size.