Thèse Cartographie Optique Bidirectionnelle des Circuits de la Mémoire et de la Motricité chez la Larve de Drosophila. H/F - Doctorat.Gouv.Fr

Établissement : Université Paris-Saclay GS Life Sciences and Health École doctorale : Signalisations et Réseaux Intégratifs en Biologie Laboratoire de recherche : Institut des Neurosciences Paris-Saclay Direction de la thèse : Claire ESCHBACH ORCID 0000000280923440 Début de la thèse : 2026-10-01 Date limite de candidature : 2026-06-22T23:59:59 Ce projet étudie la manière dont les circuits du cerveau central et les circuits moteurs interagissent pour façonner l'apprentissage, la mémoire et l'action chez les larves de Drosophila. Grâce à l'imagerie bicolore, à un modulateur spatial de lumière (SLM) et à la photostimulation en boucle fermée, nous enregistrerons et manipulerons simultanément des neurones identifiés du centre de la mémoire (les mushroom bodies) ainsi que des voies motrices, avec une haute précision spatiale et temporelle.
L'objectif 1 vise à quantifier la synchronisation entre les neurones de la mémoire et les motoneurones au cours de l'activité spontanée. L'objectif 2 vise à déterminer comment la sortie motrice exerce un rétrocontrôle sur le traitement de l'information dans le cerveau central, en utilisant une activation optogénétique structurée des motoneurones. L'objectif 3 examine comment les signaux descendants issus du cerveau modulent l'activité motrice, grâce à une stimulation en temps réel en boucle fermée réalisée avec un système à deux photons.
Ce projet générera un ensemble de données fonctionnelles reliant le traitement central de l'information aux dynamiques motrices, ouvrant la voie au développement de modèles computationnels de l'intégration sensorimotrice. Understanding how central brain processes influence action remains a fundamental challenge in neuroscience. Positive expectations bias animals toward approach and negative expectations toward avoidance [1-3], but these relationships are probabilistic and mediated by complex neural pathways. Nevertheless, many learning models assume a relatively direct transformation of memory signals into motor commands [4,5]. Likewise, although oscillatory activity in memory- and attention-related brain regions structures cognition [6,7], its interaction with rhythmic locomotor behavior remains poorly understood.
Despite major advances in systems and computational neuroscience, the mechanisms through which central brain dynamics shape motor circuits, and how motor activity feeds back to influence cognition, remain unclear. Addressing this question requires tools capable of both monitoring and manipulating neuronal populations with high spatiotemporal precision.
The Drosophila larva offers a powerful model system [8]. Its nervous system has been mapped at synaptic resolution [9], and both memory [10] and locomotor circuits [11,12] are well characterized. Recent genetic and optical advances [13-16] now enable cell-specific recording and stimulation, allowing cognition-action interactions to be studied at single-cell resolution. Insights from this tractable system may reveal general principles applicable to vertebrate brains.
Previous studies showed that output neurons of the larval mushroom body (MB), a key learning center, influence turning behavior [3]. However, the causal mechanisms linking memory and motor circuits remain unknown. While connectomic reconstructions have identified bidirectional anatomical pathways between these regions [9], the functional dynamics of information flow have yet to be determined.
To address this gap, we will combine dual-color two-photon imaging [17], spatial light modulation (SLM) [15], and real-time optogenetic control [18] to simultaneously monitor and manipulate identified neurons involved in memory and locomotion. By enabling causal interrogation of information flow in both directions (memorymotor and motormemory), this approach moves beyond correlative and pan-neuronal studies toward a mechanistic understanding of cognition-action coupling. Aim 1: Determine synchronicity between memory and motor neurons. We will monitor calcium dynamics in neurons labeled with distinct fluorescent sensors, manipulate neuro-modulation pharmacologically, and develop analysis tools to quantify synchronization between brain and motor activity.
Aim 2: Test ascending motor-to-central brain influences. We will photoactivate motoneurons with spatial light modulation to mimic motor programs, and assess how these signals are encoded in the memory center.
Aim 3: Test descending brain-to-motor effects. We will activate memory neurons while monitoring fictive locomotion, and use closed-loop optogenetics on a two-photon microscope to determine how descending signals modulate ongoing turns. - Dual-color two-photon imaging: Using genetic tools in Drosophila, we will express fluorescent activity reporters and optogenetic actuators in distinct neuronal populations, enabling simultaneous recording and manipulation of memory and motor circuits with fast volumetric imaging.
- Patterned photostimulation: Spatial light modulation (SLM) will be used to selectively activate defined neurons or subnetworks. Experimental parameters will be optimized to reproduce motor-related activity patterns and evoke locomotor responses.
- Closed-loop control: Real-time photostimulation will be applied during ongoing fictive motor activity, allowing targeted perturbation of memory-circuit output neurons at specific behavioral phases.
- Data analysis: We will develop computational methods to quantify neural synchrony, coupling, and information flow between memory and motor networks.

Un intérêt fort pour la technologie et une formation en neuroscience, biophysique et/ou ingénierie.
Une expérience en optique, en recherche expérimentale, travail avec drosophile, analyse de données, programmation est appréciée et sera développée plus avant lors de la thèse.