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Collaboration Team Beyeler in Nature:
Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions. However, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons. Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). This data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.

Interview de Nora Abrous, Directeur de recherche à l'Inserm au Neurocentre Magendie à Bordeaux. Elle est notamment spécialiste en neurobiologie du développement, mémoire et système de mémoire, vieillissement cérébral, apprentissage, vulnérabilité et addictions. Elle dirige l'équipe "Neurogenèse et physiopathologie".
Émission autour du cerveau, de la mémoire et du vieillissement sur France Bleu

Team “Neurogenesis and pathophysiology”. Neurocentre Magendie / Bordeaux Neurocampus:

The dentate gyrus (DG) of the hippocampus is one of the few mammalian brain structures where neurogenesis is maintained throughout the lifetime of individuals. Indeed the dentate granule cells (GCs), the main neuronal cell type in the DG, are generated via several distinct phases occurring during late embryogenesis, the early postnatal life, the juvenile period and throughout adulthood. Because of this continuous addition of new cells, the DG appears as a heterogeneous structure composed of different populations of granule neurons. Whether these different populations have similar or distinct structural and functional properties is still a matter of debate. Surprisingly, although most dentate GCs are generated during development, little was known about their properties compared to adult-born neurons. Nevertheless, it was generally admitted that these populations are morphologically indistinguishable once mature. However a detailed and extensive analysis of developmentally-born neurons was lacking for proper comparison.

In this study, we used in vivo electroporation to label dentate GCs generated in mouse embryos (E14.5) or in neonates (P0) and followed their morphological development up to 6 months after birth. Importantly, we highlight for the first time major morphological differences with GCs born during the juvenile period (P21) or during adulthood (P84). Importantly, we also identified different morphological parameters that can be used to predict the birthdate of granule neurons in adult brain sections. In addition, our data indicate that two other poorly studied populations of GCs in the DG, the semilunar and hilar granule cells are generated during the embryonic and the neonatal periods respectively. Thus, our findings provide new insights into the development of the different populations of granule neurons in the DG and open new questions regarding their function in the brain. Indeed, the dendritic tree determines the amount and specificity of inputs a neuron receives and is involved in sophisticated signal processing and neural computation. Consequently, mature dentate GCs born at embryonic, neonatal or adult stages might contribute differently to hippocampal function. Future analyses of the inputs and functional properties of the different populations of GCs using in vivo electroporation might help to address this controversial question.(Pictures : Thomas Kerloch, Nora Abrous, Emilie Pacary)

Dentate Granule Neurons Generated During Perinatal Life Display Distinct Morphological Features Compared With Later-Born Neurons in the Mouse Hippocampus. Thomas Kerloch, Solène Clavreul, Adeline Goron, Djoher Nora Abrous, Emilie Pacary. Cereb Cortex. 2018 Sep 12. doi: 10.1093/cercor/bhy224.

Busquets-Garcia A, Oliveira da Cruz J, Terral G, Pagano Zottola AC, Soria-Gómez E, Contini A, Martin H, Redon B, Varilh M, Ioannidou C, Drago F, Massa F, Fioramonti X, Trifilieff P, Ferreira G*, Marsicano G* (2018).Hippocampal CB1 receptors control incidental associations. Neuron

The team of Ian Wickersham at MIT developped a new generation of non toxic rabies vectors. Anna Beyeler was part of the team showing that neurons were still functioning normally up to four months after infection. In this new construct the gene coding for the polymerase necessary for transcribing viral genes was deleted. Without this gene, the virus becomes less harmful and infected cells can survive much longer.

Dix ans pour mettre au point une gélule qui peut changer la vie de beaucoup d'addicts, une vie qui peut tourner au cauchemar.
C'est un travail d'équipe au long cours qui a ses racines à Bordeaux. Au cours de ses recherches sur les effets du canabis, l'équipe du Neurocentre Magendie a découvert que sa prise entraîne la production dans le cerveau d’une molécule appelée prégnénolone. Elle a pour effet naturel de défendre l’organisme contre les effets de cette drogue. Une solution pour soigner l'addiction au cannabis. Impossible de l'utiliser en tant que telle, elle ne s'y prête pas. Les chercheurs, fédérés autour de Pier-Vincenzo Piazza, directeur de recherche Inserm, ont donc trouver la parade...

Notre publication parue en Avril 2017 dans Nature Communications porte sur un nouveau rôle de la
protéine Gpsm2 dans le contrôle de la dynamique du cytosquelette d’actine. Elle est relayée par le
Magazine Sciences et Santé de l'Inserm.

Press review
La publication de l'équipe de Cyril Herry dans Nature relayée par Sciences et Santé
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L'équipe de Cyril Herry publie une nouvelle fois ses travaux dans Nature. La publication de juillet 2016 porte sur les mécanismes de l'expression de la peur dans le cortex préfrontal dors médian. Elle est relayée par le Magazine Sciences et Santé de l'Inserm.

Erwan Bézard, directeur de l'IMN, est à l'honneur dans le magazine de l'Inserm pour ses travaux sur les maladies neurodégénératives.
Retrouvez la vidéo que la Fédération Bordeaux Neurocampus lui consacrait ici :

Nature. 2016 Jul 21;535(7612):420-4.
Prefrontal neuronal assemblies temporally control fear behaviour.
Dejean C, Courtin J, Karalis N, Chaudun F, Wurtz H, Bienvenu TC, Herry C.

Over the past decades, numerous studies demonstrated a critical role of the medial prefrontal cortex (mPFC) in regulation emotional behaviour, in particular learned fear responses. In these studies, in which the neuronal substrates of aversive learning were investigated, encoding of fear behavior was assumed to rely on the activity of single neurons through a rate coding mechanism in which the sole firing rate determine the behavioral output. This form of neuronal cording is strongly limited by the fact that over long distances, rate codes are not optimal for the fast information transmission that is required for rapid behavioural adaptation when facing threatening stimuli. In addition to this rate coding mechanism, neurons with different and specific firing sequences may cooperate and collectively provide information, a phenomenon referred to as "temporal coding".

In temporal coding, precise timing of firing is important, whereas average firing rates can remain stable. Assemblies of neurons enable temporal coding, and one of its obvious advantages is its great flexibility. Thus, neurons might rapidly switch between multiple functional networks according to sensory and internal inputs and determine specific behavioral outputs. Brain oscillations are thought to be instrumental in temporal coding by binding cell assemblies, organizing individual firing into meaningful collective activity, and coordinating remote areas. Whereas temporal coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour is virtually unknown.

To address this question we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses.