Raouf Issa - Maintenance of the nervous system & behaviour

We are interested in how neurons after their formation maintain the specialisation of their circuits across animal adaptations, and how the mechanisms underlying these adaptations determine behavioural states throughout life.

The nervous system is made up of several types of neurons, whose circuits are structurally and functionally tuned by the genome to produce behaviours, most notably motor ones. This regulation is critical to maintain neuronal circuit specialisations during the life of the animal. Yet, how such maintenance is achieved across developmental (e.g. puberty), pathological (e.g. neurodegenerative disorders) or environmental (e.g. climate) adaptations remain an open and fundamental question in modern neuroscience.

We use the fruit fly Drosophila melanogaster and its motor system as an experimental model to address this question. The motor system of D. melanogaster is less complex than that of humans, and presents highly conserved biological and physiological characteristics, including genetics (e.g. homeotic or autophagy genes), cellular (e.g. dopaminergic, or glutamatergic neurons) and behaviours (e.g. locomotion or posture). Interestingly, the impressive toolbox available in the fly motor system, from the transcriptome through the connectome to the ability to monitor and manipulate individual neuronal populations, provides an extraordinary opportunity to study the maintenance mechanisms of motor circuits through adaptations.

Here, we employ a transdisciplinary approach in Drosophila melanogaster, combining a variety of methodologies, including genetic manipulations, modern molecular biology techniques, advanced microscopy imaging of genetically encoded biomarkers and behavioural analysis to study four aspects that are particularly relevant in the context of the nervous system maintenance and the research mission of the Brain Plasticity Lab as a whole : (a) how neuronal circuit specialisations that determine adult motor behaviours emerge from the earliest stages of development; and (b) how these specialisations are maintained later stages, despite the transformative process of the nervous system during metamorphosis. With these investigations, we will then define the temporal genetic programs that ensure the adaptations of neuronal circuit structures and function across developmental transitions of the organism. (c) We also study the maintenance of motor circuits in the D. melanogaster models of neurodegenerative diseases. This will allow us to define general principles on adaptive strategies of the nervous system to delay the onset of these disease phenotypes. Furthermore, to provide an increasingly generalised understanding of the maintenance mechanisms of circuits across different contexts, (d) we include in our investigations D. melanogaster sub-populations living in different environments – Sahara and Temperate.

Altogether, our work will provide key insights into molecular and cellular mechanisms that enable nervous systems to adapt their circuits to produce appropriate behavior in response to the demands of development, disease or environment.