Perception and Memory - CNRS URA2182  

  HEADDr LLEDO Pierre-Marie /
  MEMBERSDr ALONSO Mariana / GABELLEC Marie-Madeleine / Dr GHEUSI Gilles / Dr GRUBB Matthew
Dr MEJIA GERVACIO Sheyla Vianey / MOURET Aurélie / Dr NISSANT Antoine / Dr ORTEGA-PEREZ Inmaculada

  Annual Report

Adult Neurogenesis in the Mammalian Forebrain

In the olfactory bulb (OB), neurons are renewed during the whole life. The genetic and epigenetic determination of this permanent neuronal production, and its regulation, are still unclear. We are exploring the molecular mechanisms of this neurogenesis to define the key factors involved in cell production and characterize the maturation steps by which a stem cell becomes a functional neuron. Complementary models and experimental procedures integrate several approaches, including molecular and cellular biology, functional imaging, electrophysiology and behavioral analysis. All these methods aim at investigating the functional impact of adding new neurons to pre-existing circuits.

Stability versus flexibility

With the adult mouse OB as a model, we are addressing a series of fundamental questions concerning the role(s) that neurogenesis plays in the normal functioning of neuronal circuits: Why does neurogenesis persist in some part of the adult brain but not in other ones? Is it a recapitulation of embryogenesis or rather a unique feature of the adult forebrain? Why is it restricted, apparently, to only two specific regions in normal conditions? How do these regions balance the need for plasticity with the need to maintain already–functional information processing networks? Is neurogenesis in the adult brain a constant, restorative process, or is it flexible, producing different numbers of neurons to certain regions according to an animal’s environmental experience? And are new neurons in the adult brain born to perform a particular task not possible for mature neurons, or are they generated as flexible units to undertake whichever role their target structure is in need of most?

We have previously demonstrated that adult-born neurons integrate functionally into the adult bulbar circuit according to a unique maturation stage. The goal of our next studies consists in exploring the relation between the sequence of functional appearance of neurotransmitter receptors and normal targeting and survival of newborn neurons. As a first step, we have developed a forebrain organotypic ex vivo approach to follow the adult-generated neurons using time-lapse video imaging. Dynamic parameters of their morphological maturation will be studied using a two-photon laser scanning microscopy. This will allow a high-resolution visualization of spines, their motility, and the monitoring of [Ca2+]i transients.

This work should provide new molecular and cellular data concerning the key steps by which an adult-generated neuron can silently insert into a functional network, without disturbing its functioning. Elucidating the chain of events involved in the adult neurogenesis will help us to understand the fundamental processes employed by the adult brain to cope with an ever-changing external word. In addition, we believe that through the development of an integrated and multidisciplinary program important advances in understanding how the olfactory system process sensory information will be achieved.


Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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