Research

Our Major Goals

 

 

Recently, modern neuroscience has made considerable progress in understanding how the brain perceives, discriminates, and recognizes odorant molecules. This growing knowledge took over when the sense of smell was no longer considered only as a matter for poetry or wine industry. Over the last decades, chemical senses captured the attention of scientists who started to investigate the different stages of olfactory pathways. Distinct fields such as genetic, biochemistry, cellular biology, neurophysiology and behavior have contributed to provide a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain.

In our laboratory, the combination of these approaches has been effectively done at both the cellular and the system levels. With the adult mouse olfactory bulb 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? Together our recent descriptions of the properties of bulbar neuronal networks, and emerging principles concerning the function of local interneurons, indicate that the newborn cells play a much more complex role than that of simple gatekeepers inhibiting the olfactory bulb network.

 

 

 

 

Our experimental model
 

Our laboratory is focused on neuronal plasticity in the main olfactory bulb, the first central relay of the olfactory system where synaptic transmission between dendrites represents the major device for neuronal interaction. At this level, synaptic transmission includes both inhibitory and excitatory signals that coexist in a purposeful balance. This structure is involved not only in transmission of olfactory information but also in odor processing and memory. It receives a massive centrifugal innervation from different brain structures involved in conditional learning as well as in memory consolidation. During learning, the olfactory bulb is subjected both to plastic synaptic changes and to neurogenesis related to amnesic storage. For all these reasons and because of its relatively simple anatomical organization and easy accessibility, the olfactory bulb is our favored model system to investigate odor information coding as well as to elucidate the cellular basis of odor memory. Using a multidisciplinary approach combining molecular, cellular and behavioral levels, our goal is to determine in adult brain, how acquisition and retention of odor information can be accomplished within a neuronal network characterized by a high level of neuronal replacement.

 

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Candidate stem cells in the adult rostral migratory stream (RMS).

RMS astrocytes positive to GFAP staining (red) wereinfected witha GFP-encoding lentiviral vector (green). These cells give rise to fully-integrated neurons in the adult olfactory bulb, and can be specifically regulatedby sensory inputs.
 

 

 

A model system to study adult neurogenesis

 

 

The phenomenon of neurogenesis in adult animals, which has therapeutic potential in treating neurodegenerative diseases, leads to several questions: What controls the pattern of connections formed by new cells? How is the stability of memory and of information processing maintained when cells and synapses are constantly being lost and new ones produced?

To answer these questions we intend to investigate neurogenesis in the mammalian olfactory bulb, using a combination of computational modeling and electrophysiology. We propose to develop a detailed, biologically-realistic computational model of the olfactory bulb neuronal network, incorporating recent findings about neuronal membrane and synaptic properties, and obtaining new experimental data as necessary to constrain the model. Using this model we will investigate odor information processing, learning and memory in the olfactory bulb, and how these are affected by neurogenesis. Use of a computational model will allow us to quickly perform simulation experiments to investigate alternative hypotheses. The most promising simulation results will be tested by experimental methods: patch-clamp electrophysiology in mouse olfactory bulb slices, and possibly behavioral methods.

 

Updated on 10/03/2014

Contact us

Perception and Memory Laboratory
Institut Pasteur, Bâtiment Fernbach
25 rue du Dr. Roux
75724 Paris CEDEX 15, France

Phone: +33 (0)1 45 68 88 03
Fax: +33 (0)1 45 68 83 69
E-mail us: Isabelle Poste

p1080388-2.jpgThe Institut Pasteur is located in south of Paris.
To reach us:
- by subway: lines 6 or 12, station Pasteur.
- by bus: 89, 95

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Although we have no open positions at the moment, we always welcome applications from highly-motivated candidates.

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CNRS

Centre National de la Recherche Scientifique

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Network of European Neuroscience Institutes

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FENS

Federation of European Neurosciences

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