Persistent activation of dopaminergic neurons and its impact on behavior and neural circuitry in Drosophila larvae

Organisms have the ability to respond and adapt to different environmental contexts, which is crucial for their fitness. Sensory experiences and stimuli are detected by neurons in the peripheral nervous system and then transmitted to the central nervous system. Neurotransmitters, such as dopamine, allow for communication between neurons and have complex roles in a variety of organismal functions such as motor function, learning and memory, and mediation of reward-related behavior. Some circumstances such as disease states or exposure to neuroactive chemicals can lead to dysfunctional activity, including hyperactivity, for extended periods of time within the dopaminergic system. The effect of hyperactivation across the levels of behavior, circuit activity, and neural activity is relatively unexplored together in a single system. To investigate hyperactivation, I used neuroactive chemicals as tools to drive prolonged activation in dopaminergic circuits and record the resulting behavior using a novel robotic rig that allows for long-term behavioral assays over many hours. I find that larvae do modulate aspects of their navigation, consistent with effects of dopaminergic hyperactivity. In addition to that, long-term behavioral analysis was conducted that demonstrated shifts in the prevalence of a multitude of behavioral set points across exposure. To follow up, in vivo neural confocal microscopy was deployed during repetitive dopaminergic neural activation in order to identify sensitive neurons with single cell resolution and characterize changes within circuits. The neural activity found in the larval brain was consistent with brain regions rich in dopaminergic innervation. These experiments use novel approaches to understand the impact of hyperactivation on multiple levels of the dopaminergic neural system.