Abstract

How the brain resolves conflicting situations is a fascinating question that remains unanswered. We do not know yet how alternative options are represented in the brain, how specific actions get prioritised, and how these processes are affected in neuropathologies, such as Parkinson’s disease and Alzheimer’s disease. I have created an assay in which Drosophila males are presented with visual threats during courtship, which creates a conflict between reproduction and survival. Capitalising on refined genetic tools, this assay offers a great opportunity to study the neural mechanisms that govern the selection between competing options. Preliminary data shows that P1 cells are strong candidates mediating the choice between courting and escaping a threat. We will carry out a targeted behavioural screen to identify the inputs to this neural population. From an in silico screen of 3500 Gal4 fly lines targeting defined cells, I have selected 40 lines based on their potential connectivity with P1 cells. Using optogenetics, we will identify cells that, when activated or silenced with light pulses, prevent males from blocking courtship in response to the threat. We will also test 40 Gal4s that label neuromodulatory cells likely interacting with P1 cells. Next, we will ask if candidate cells respond to the threat in live imaging studies using Ca2+ indicators, and test if they are linked with the courtship circuitry using pre and post-synaptic markers and sybGRASP (to test potential synaptic connections). To probe if candidate neurons are functionally linked, we will optogenetically manipulate the activity of upstream cells, and monitor the responses in downstream cells with Ca2+ imaging. This will allow us to build a map of the neural network of action-selection. Finally, we will test how external factors and internal state variables modulate action-selection. This study will provide insights into fundamental brain processes that may work in other animals, including humans.