Circuit mechanisms of behavioural variability in Drosophila flight.

Introduction

While sensory systems report sensory input with high reliability, behavioural responses are inherently variable. How this variability arises and how behavioural decisions are formed is not well understood in any organism.

Research Model

I will use the fruit fly Drosophila as a model system to study how a specific behaviour is initiated depending on external stimuli and behavioural state.

Behavioural Observation

During flight, flies change direction to avoid dangers or search for food with a fast turning response called saccade. This behaviour can be replicated in head-fixed flying flies, where saccades are measured as fast changes in wing stroke amplitude, which allows for simultaneous recordings of neuronal activity.

Neuronal Circuits

However, the neuronal circuits underlying the execution of saccades in the fly brain are not known. Previously, I have discovered a descending neuron whose activity is strongly correlated with saccadic turns during head-fixed flight.

Methodology

I will use novel anatomical tools and the available EM data sets to find the neurons that provide input to this descending neuron and which control saccades.

1. I will then record their activity using:

   • 2-photon Calcium imaging of a genetically encoded indicator
   • Whole-cell patch-clamp recordings during flight.

2. At the same time, I will present a panel of multisensory stimuli while monitoring turning behaviour.

This will allow me to test under which stimulus conditions and internal states these neurons are active and whether their activity is more closely correlated with sensory input or behavioural output.

Genetic Manipulation

To test for the contribution of these neurons to the execution of saccades, I will use genetic tools to manipulate their activity during tethered as well as free flight.

Conclusion

This comprehensive approach will allow me to study which neurons control saccadic turns and at which processing stage behavioural decisions are made. It will provide general insights into how information is processed along the sensory-to-motor pathway and how behaviour is initiated.