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A developmental engram for the organization of adult hippocampal circuits

Project description

Neuronal birthdate and brain function

The hippocampus is a complex part of the brain that plays a central role in learning and memory formation as well as spatiotemporal cognition. Hippocampal activity and dynamics is an area of active interest and research. Funded by the European Research Council, the NeuroPioneers project is working under the hypothesis that the timing of neuron birth during development is an important factor in determining the function of these neurons in adulthood. Researchers will employ a multidisciplinary approach to investigate how highly active neurons in the mouse brain contribute to brain neuronal network dynamics. Findings will provide fundamental insight into brain function with ramifications for neurological disorders including Alzheimer's disease.


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.

Host institution

Net EU contribution
€ 1 996 947,00
75654 Paris

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Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Total cost
€ 1 996 947,00

Beneficiaries (1)