Dopaminergic basis of behaviour

The neurotransmitter dopamine is involved in a range of behaviours including locomotion, addiction and reward. Abnormal dopamine signalling is also implicated in human disease - for example, loss of function of the Dopamine transporter protein (that controls the timing of neurotransmitter signalling) can lead to Dopamine Transporter Deficiency Syndrome (DTDS), an early onset form of Parkinson's disease. In this project we will use zebrafish, a popular model for neuroscience research, to investigate dopaminergic signalling in both wild-type zebrafish and in animals lacking the dopamine transporter gene.
We will first use neurochemistry techniques to characterise the release of dopamine at the synapse. We will compare control animals to fish treated dopamine reuptake inhibitors. We will then use a virtual reality setup to measure dopamine release in response to moving stimuli such as a looming shadow or food-like image. This information will allow us to compare dopamine signalling dynamics between zebrafish and other vertebrate model organisms.
We will then characterise a dopamine transporter mutant line that is available in our laboratory to establish a new model for DTDS. There are currently few treatments available for this disorder and more animal models are needed for research. We will characterise the release of dopamine in these mutants using the neurochemistry techniques established above as well as recording their behavioural profile (including aggression, locomotion and anxiety).
Finally, we will characterise a second zebrafish mutant line called leucine rich repeat transmembrane neuronal 4 like 1. The lrrtm4l1 gene was identified in human patients that exhibit heightened aggression. We will examine the behaviour of these mutants across their lifespan, including locomotion, anxiety, aggression and social behaviour. We will also use neurochemistry and antibody labelling to investigate monoamine signalling in the brain.