NeuroPSI – Université Paris-Saclay

The endogenous circadian clock is a fundamental system present in the majority of living organisms, functioning to regulate and synchronize daily rhythms across physiological and behavioral processes. This intricate temporal regulation of the biological processes is driven by a molecular mechanism involving transcriptional-translational feedback loops, generating oscillations of clock gene expression. In Drosophila melanogaster, this self-sustaining mechanism operates within a subset of approximately 150 brain neurons termed clock neurons. These neurons synchronize their molecular clocks through inter-neuronal communication, enabling the brain clock as a unified neuronal network that generates robust circadian rhythms. A pivotal feature of the circadian clock is its ability to synchronize with external environmental cues, enabling organisms to proactively adapt to environmental changes by aligning behavior and physiology with specific times of the day. Circadian clocks are entrained by external synchronizing factors known as zeitgebers, with light being the most potent and reliable of these cues. Beyond light, other cues such as temperature, or social interactions, also play a role in facilitating circadian entrainment. In Drosophila, circadian photoreception encompasses numerous pathways that utilize diverse photoreceptors to adjust clock synchronization finely. This sensory input can be broadly categorized into two pathways: one involving the blue-light-sensitive photoreceptor CRYPTOCHROME (CRY), expressed in the majority of clock cells, and the other utilizing the Rhodopsin-mediated visual input pathways.

This thesis delves into the multifaceted nature of circadian entrainment, emphasizing the various light input pathways that synchronize the neuronal clocks to external light-dark cycles. Three studies were conducted as part of this thesis, exploring distinct aspects of this sensory system. The first project unravels the contribution of ocelli-mediated light input, revealing Rh2-expressing ocelli’s role in the photoentrainment of fly locomotor behavior and the underlying neural circuit. The second project investigates non-cell autonomous CRY-mediated light input, shedding light on collaborative clock neuron functions and the neural mechanisms distributing CRY signals in the brain clock network. The third study focuses on the still unknown neural circuit that connects the retina to clock neurons, particularly focusing on the role of R8 photoreceptors in transmitting signals to clock neurons. Collectively, these data advance our understanding of how biological rhythms synchronize with ambient light conditions by uncovering the neural mechanisms and molecular processes through which clock neurons perceive diverse light inputs.

Composition du Jury

• • Mme Charlotte HELFRICH-FÖRSTER Theodor-Boveri Institute, University of Würzburg – Rapportrice & Examinatrice
  • M. Xavier BONNEFONT Institut de Génomique Fonctionnelle (IGF), Cnrs UMR 5203- Université de Montpellier – Rapporteur & Examinateur
  • M. Daniel VASILIAUSKAS INSERM, Université Paris-Saclay – Examinateur
  • M. Jean-René MARTIN CNRS, Université Paris-Saclay – Examinateur

et

• M. François ROUYER (Institut NeuroPSI, Saclay)