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

Project description

Studying neuronal mechanisms of behavioural choice

Behavioural choice plays a crucial role in an animal’s survival. However, the related fundamental neuronal mechanisms are not well understood because the circuits involve several brain regions. While the connectome structurally connects all potential circuits, it is insufficient to drive functional models. Recent developments in microscopy allow neuronal activity monitoring across entire brains. The EU-funded BICE project proposes a method to observe and identify neurons with significant activity standards by which the same sample goes through whole-brain functional imaging and subsequent electron microscopy imaging. To identify circuit mechanisms that promote one action while repressing others, the project will study the neuronal mechanisms of behavioural choice in Drosophila melanogaster larvae.

Objective

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.

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution
€ 212 933,76
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76