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Séminaire - Zena Vexler
21 oct. 2016 à 11:30 - Institut François Magendie
how maturation of microglial cells...► En savoir +
Cajal Course 2016: Hippocampus
8 juil. 2016
expert lectures from the leaders of the field and ...► En savoir +
L'INCIA - PAM propose une nouvelle formation
11 oct. 2016
cadre clinique, industriel ou de recherche...► En savoir +
Fête de la Science 2016 Bordeaux Neurocampus un succès fou !
15 oct. 2016
Bordeaux Neurocampus tous azimuts► En savoir +
Lunch with a researcher
20 oct. 2016
Etudiants, venez échanger dans un climat convivia...► En savoir +
Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors.Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors.
Synaptic plasticity in the autoassociative network of recurrent connections among hippocampal CA3 pyramidal cells is thought to enable the storage of episodic memory. Impaired episodic memory is an early manifestation of cognitive deficits in Alzheimer's disease (AD). In the APP/PS1 mouse model of AD amyloidosis, we show that associative long-term synaptic potentiation (LTP) is abolished in CA3 pyramidal cells at an early stage. This is caused by activation of upregulated neuronal adenosine A2A receptors (A2AR) rather than by dysregulation of NMDAR signalling or altered dendritic spine morphology. Neutralization of A2AR by acute pharmacological inhibition, or downregulation driven by shRNA interference in a single postsynaptic neuron restore associative CA3 LTP. Accordingly, treatment with A2AR antagonists reverts one-trial memory deficits. These results provide mechanistic support to encourage testing the therapeutic efficacy of A2AR antagonists in early AD patients. Viana da Silva S, Haberl MG, Zhang P, Bethge P, Lemos C, Gonçalves N, Gorlewicz A, Malezieux M, Gonçalves FQ, Grosjean N, Blanchet C, Frick A, Nägerl UV, Cunha RA, Mulle C.
Nat Commun. 2016 Jun 17
Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines.Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines.
Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain. Pfeiffer T, Avignone E, Nägerl UV.
Sci Rep. 2016 Sep 8
P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons.P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons.
Plasticity at excitatory synapses can be induced either by synaptic release of glutamate or the release of gliotransmitters such as ATP. Recently, we showed that postsynaptic P2X2 receptors activated by ATP released from astrocytes downregulate synaptic AMPAR, providing a novel mechanism by which glial cells modulate synaptic activity. ATP- and lNMDA-induced depression in the CA1 region of the hippocampus are additive, suggesting distinct molecular pathways. AMPARs are homo-or hetero-tetramers composed of GluA1-A4. Here, we first show that P2X2-mediated AMPAR inhibition is dependent on the subunit composition of AMPAR. GluA3 homomers are insensitive and their presence in heteromers alters P2X-mediated inhibition. Using a mutational approach, we demonstrate that the two CaMKII phosphorylation sites S567 and S831 located in the cytoplasmic Loop1 and C-terminal tail of GluA1 subunits, respectively, are critical for P2X2-mediated AMPAR inhibition recorded from co-expressing Xenopus oocytes and removal of surface AMPAR at synapses of hippocampal neurons imaged by the super-resolution dSTORM technique. Finally, using phosphorylation site-specific antibodies, we show that P2X-induced depression in hippocampal slices produces a dephosphorylation of the GluA1 subunit at S567, contrary to NMDAR-mediated LTD. These findings indicate that GluA1 phosphorylation of S567 and S831 is critical for P2X2-mediated AMPAR internalization and ATP-driven synaptic depression. Pougnet JT, Compans B, Martinez A, Choquet D, Hosy E, Boué-Grabot E.
Sci Rep. 2016 Sep 14
Prefrontal neuronal assemblies temporally control fear behaviour.Prefrontal neuronal assemblies temporally control fear behaviour.
Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here 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. Dejean C, Courtin J, Karalis N, Chaudun F, Wurtz H, Bienvenu TC, Herry C.
Nature. 2016 Jul 21
Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy.Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy.
Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation. Bassil F, Fernagut PO, Bezard E, Pruvost A, Leste-Lasserre T, Hoang QQ, Ringe D, Petsko GA, Meissner WG.
Proc Natl Acad Sci USA. 2016 Aug 23
19 oct. 2016
Robert Dantzer montre que des souris transgéniques dépourvues de lymphocytes T sont incapables de se remettre d’un stress inflammatoire.. ► Lire la suite
19 oct. 2016
ce fardeau est due à l’érosion des capacités intellectuelles, calculées en points de quotient intellectuel (QI), des enfants exposés...► Lire la suite
13 oct. 2016
L'empathie d'un rongeur pour son petit est le même que celui qui s'effectue dans le cerveau de l'Homme... ► Lire la suite
EMPLOIS - JOB OPPORTUNITIES +
Post-doc positions open / Team leader
Recherchons ! Bordeaux Neurocampus:
en ligne le 19 sept 2016 ....Recherchons: Chef de projet du centre d’excellence sur les maladies neurodégénératives CHU de Bordeaux Hôpital Pellegrin - Institut des Maladies Neurodégénératives
Stages / Internship....
Job opportunities outside Bordeaux...Post doctoral position in Grenoble / on line September 15 / 2016 / Transport and Intracellular Distribution of Zinc in Neurons....
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