Dr camilla Larsen, Dr M Meyer
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Animals including humans make choices continuously based in past experience, present sensory input and internal state. A major goal in neuroscience is to identify the neural circuits underlying goal directed choices and to elucidate the neural computation driving goal orientated behaviour. Research in my lab has revealed that the Drosophila larvae display goal orientated choice behaviours. Drosophila is particularly well suited to study neural computation due to the numerical simplicity of the brain which supports a range of stereotypic well characterised behaviours and the range of tools which allow us to specifically modulate neural activity in subsets of neurons. In fact neural activity can be modulated at single cell level allowing us to investigate in detail how information is processed at the circuit level. We use olfaction as a paradigm to study how past experience (learning) and present stimuli (odour) direct navigation. We train larvae to associate an odour with the absence of an award and find that after training larvae will actively avoid the odour in search of a reward because they have learned that reward is never present when the odour is presented. This type of choice behaviour is called outcome-specific conditioned inhibition. However if larvae do not find the reward they will change their mind and choose to navigate the odour gradient to find the location of the odour which in naïve animals signals the location of potential food.
This project aims to investigate the switch from avoiding the odour to odour attraction and to understand the neural computation underlying this behavioural switch. The Drosophila learning and memory centre is called the Mushroom body (MB) and we have identified potential candidate neurons within this structure which could be specific the outcome-specific conditioned inhibition. In addition recently every output neuron from the MB has been mapped and tools are available to selectively modulate each of these output neurons. This project will use behavioural assays and functional imaging in combination with light sensitive neural modulators to identify the neural components underlying the switch from outcome-specific conditioned inhibition to odour attraction. The student will first silence different subgroups of MB neurons and then test if they can learn to avoid the odour in search for reward. Once the MB neurons responsible for outcome-specific conditioned inhibition have been identified we can activate them using light sensitive ion channels. We can then measure neural activity in output neurons to identify which neurons are connected to the MB neurons responsible for outcome-specific conditioned inhibition. At this stage we have identified the neural components of the behaviour. Next the students will measure neural activity in these neurons after learning to describe how neural activity change during the time window of the behavioural switch. This will tell us whether different output neurons change activity during the critical time period. Once the neural code has been identified we can artificially induce the change in neural activity in naïve animals to show that a particular response profile of a neuron can drive specific behaviour.
As part of the project the students will also learn general techniques such as fly genetics, immunohistochemistry and microscope techniques. The student will be actively encouraged to present their data at conferences and local seminar series and to grow and mature as a scientist.