Neural Mechanisms of Action-Selection During Sensory Conflict

Prioritising the most urgent goal according to the context and physiological needs is crucial for the success of any organism.

Action-selection processes are often disrupted in neuropathologies, such as Parkinson's disease, Alzheimer's disease and addiction; however, the underlying neuronal mechanisms are not well understood. Crucially, how the brain evaluates sensory conflicting options and selects an appropriate action remains unknown.

I will tackle this question using a novel assay in which Drosophila fruit fly males are confronted with visual threats during courtship, which creates a conflict between survival and reproduction.

Capitalising on refined genetic tools, I aim to unravel neural mechanisms that govern the selection between competing options.

I will carry out a behavioural screen to identify neurons that allow the fly to choose between courting a mate and escaping a threat.

From an in silico screen of Gal4 fly lines targeting defined cells, I will select lines based on their potential connectivity with courtship-command neurons.

Using optogenetic tools, I will identify neurons that, when activated or inhibited, prevent males from blocking courtship in response to the threat.

Next, I will ask if these cells respond to the threat in live Ca2+ imaging studies, and test if they are linked with the courtship circuitry using pre and post-synaptic markers and GRASP (to test potential synaptic connections).

To probe if candidate neurons are functionally linked, I will manipulate the activity of upstream cells, and test the responses in downstream cells with Ca2+ imaging. This will allow me to build a map of the neural network of action-selection. Finally, I will test how external and internal state variables modulate action-selection.

This study will provide insights into fundamental brain processes that may work in other animals, including humans.