Description du projet
Étudier l’hippocampe dans une perspective développementale
L’hippocampe est la partie du cerveau responsable de l’apprentissage, des émotions et de la formation de la mémoire. De nouvelles preuves laissent penser que le développement joue un rôle clé dans la fonction de l’hippocampe. HOPE est une initiative financée par l’UE qui vise à étudier les circuits neuronaux de l’hippocampe et à déterminer s’ils se forment au cours du développement ou s’ils sont façonnés par l’expérience. Le projet développera des méthodes innovantes pour tracer des clones neuronaux génétiquement marqués de la naissance à l’âge adulte. Ainsi, HOPE mettra en lumière l’émergence et la plasticité des circuits neuronaux dans des contextes physiologiques et pathologiques.
Objectif
We aim at shedding a unique light on hippocampal function at circuit level through the design of a novel method to trace the construction of brain circuits in health and disease based on hybrid multiphoton in vivo longitudinal color imaging of the dynamics and structure of genetically-tagged neuronal clones from birth into adulthood. This is made possible by the exceptional interdisciplinary collaboration of three labs with expertise in advanced optical microscopy, genetic engineering and systems developmental neuroscience. Our novel methodology, applied here to the hippocampus, will pioneer a new way to track the emergence and plasticity of heterogeneous neuronal circuits as these progressively give rise to function in physiological and pathological contexts, thus bridging the gap between early development and adult circuit physio-pathology. This will enable us to revisit adult hippocampal function from a developmental perspective. The hippocampus is classically described as providing a cognitive map of space, involved in navigation, learning, and episodic memory. However, a more computational and less representational vision of its role presently emerges in which its circuits are best described as producing sequences of neuronal activation arising from the interaction between external contextual inputs and internally-generated preconfigured dynamics. Converging work including ours leads us to hypothesize that internally preconfigured assemblies, shaped by their developmental journey, are the basic modules of hippocampal function. In this context, we will use our new approach to address three interrelated questions: 1) Are assemblies shaped by specific circuits in the adult hippocampus (objective A)? 2) Are they prewired or shaped by experience (objective B)? 3) What is their patho-physiological significance (objective C)? Addressing these major issues raises a timely challenge in both optics and genetic engineering at the core of this synergistic proposal.
Champ scientifique
Mots‑clés
- nonlinear microscopy
- multiphoton microscopy
- adaptive optics
- light-sheet microscopy
- tissue imaging
- harmonic generation microscopy
- bioimage informatics
- large image data
- cell lineage
- clonal analysis
- connectomics
- neurodevelopement
- brainbow
- genetic engineering
- calcium imaging
- hippocampus
- development
- circuits
- neuronal dynamics
Programme(s)
Thème(s)
Régime de financement
ERC-SyG - Synergy grantInstitution d’accueil
75794 Paris
France