BICE · Circuit mechanisms for behavioral choice from complete CNS activity and connectivity maps

Behavioral choice is essential for an animal's survival, but the underlying neuronal mechanisms are poorly understood. A main obstacle is that the circuits involve many brain regions. Hence investigation necessitates the study of whole-brain connectivity and dynamics. Although the connectome structurally links all potential circuits, it is insufficient for constraining functional models and must be complemented by neuronal recordings during behavioral tasks. Furthermore to test models it is necessary to manipulate identified circuit elements. Recent advances in microscopy facilitate the acquisition of complete connectomes for small animals and support neuronal activity monitoring across entire brains. The challenge remains to directly combine these techniques in the same organism. We have developed a method for observing and identifying neurons with interesting activity patterns, whereby the same sample undergoes whole-brain functional imaging and subsequent electron microscopy imaging. We propose utilizing this approach to study the neuronal mechanisms of behavioral choice in Drosophila melanogaster larvae, an ideal model system for this work. We developed a paradigm to study the choice between one of five possible exclusive actions that occur in response to the same stimulus. The aim is to identify circuit mechanisms that promote one action while suppressing all others. Based on function, structure, and neurotransmitters, we will develop models for these competing circuit motifs. Specifically, we will correlate neuronal activity with each action and combine this information with connectomic data. We assume that the competing circuits interact by inhibition, which were described before in literature. These will be tested by genetic manipulation of specific circuit elements, which will alter the probability of certain behaviors. In conclusion, we combine functional and structural information in the same organism to study the neuronal mechanisms of behavioral choice.