Functional analysis of neural circuitry in the larval zebrafish brain. (360G-Wellcome-082675_Z_07_Z)

I will establish a novel system to study learning-associated neural plasticity that exploits the many advantages of the larval zebrafish model. I will perform live imaging of circuit activity associated with a complex behaviour. This will enable learning-associated changes in neural responses to be followed in real time and integration of changes in behavioural outputs and circuit physiology to be linked to the molecular-cellular properties of identifiable neurons. Specific goals: 1) I will develop an appetitive, associative learning paradigm that utilises a novel method to non-invasively deliver reinforcing stimuli. Specific visual cues will be presented to immobilised larvae, shortly followed by light-stimulated activation of dopaminergic reward circuitry. 2) I will use high-resolution functional imaging to quantify stimulus-evoked neuronal activity at loci throughout the larval brain before, during and after training. This will resolve the spatio-temporal sequence o f changes in neuronal response properties underlying the acquisition of the learned behaviour. 3) I will begin to elucidate how the different neurons comprising the functional circuit interact during learning. How are cells showing related changes in activity interconnected? Which neurons display functional plasticity and represent loci of memory storage? What are the morphological and molecular-genetic changes underlying functional plasticity?