Description du projet
Date de naissance des neurones et fonction cérébrale
L’hippocampe est une partie complexe du cerveau qui joue un rôle central dans l’apprentissage et la formation de la mémoire ainsi que dans la cognition spatio-temporelle. L’activité et la dynamique de l’hippocampe constituent un domaine d’intérêt et de recherche actif. Financé par le Conseil européen de la recherche, le projet NeuroPioneers s’appuie sur l’hypothèse que le moment de la naissance des neurones au cours du développement est un facteur important pour déterminer la fonction de ces neurones à l’âge adulte. Les chercheurs adopteront une approche multidisciplinaire pour étudier comment les neurones hautement actifs présents dans le cerveau de la souris contribuent à la dynamique du réseau neuronal cérébral. Les résultats fourniront des informations fondamentales sur le fonctionnement du cerveau, avec des ramifications en matière de compréhension des troubles neurologiques, y compris la maladie d’Alzheimer.
Objectif
Most adult cortical dynamics are dominated by a minority of highly active neurons distributed within a silent neuronal mass. If cortical spikes are sparse, spiking of single distinct neurons can impact on network dynamics and drive an animal’s behavior. It is thus essential to understand whether this active and powerful minority is predetermined and if true to uncover the rules by which it is set during development. I hypothesize that birthdate is a critical determinant of neuronal network function into adulthood. More specifically, I reason that neurons that are born the earliest are primed to participate into adult network dynamics. The goal of this proposal is to challenge this original hypothesis, which is considerably fed by our past work aiming at understanding how cortical networks function and assemble during development. Hence, we have shown that an early birthdate: (1) specifies the specialization of GABA neurons with a hub function, that orchestrate perinatal network dynamics in the mouse hippocampus (Bonifazi et al. 2009) and develop into long-range projecting GABA neurons into adulthood (Picardo et al. 2011); (2) delineates a subtype of CA3 glutamate neuron with a “pacemaker” function in the absence of fast GABAergic transmission (Marissal et al. 2012). We will analyze the structure and function of early born GABA and glutamate neurons, in the adult mouse hippocampus, mainly in vivo, where the extensive and long-range connectivity of these cells is preserved. To this aim, we have translated from the in vitro to the in vivo situation, our multidisciplinary method to investigate structure-dynamics relationship in cortical networks. Using this approach, we have recently shown that, in the absence of external landmarks, distance is encoded within the hippocampus in recurrent and self-circumscribed sequences of neuronal activation. Our proposal will specifically examine the recruitment of early born neurons in this sparse network dynamics pattern.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
75654 Paris
France