News & Events

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission. Murphy-Royal C, Dupuis JP, Varela JA, Panatier A, Pinson B, Baufreton J, Groc L, Oliet SH. Nat Neurosci. 2015 Feb;18(2):219-26. doi: 10.1038/nn.3901. Epub 2015 Jan 12.

Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored. We found that GLT-1 transporters were highly mobile on rat astrocytes. Surface diffusion of GLT-1 was sensitive to neuronal and glial activities and was strongly reduced in the vicinity of glutamatergic synapses, favoring transporter retention. Notably, glutamate uncaging at synaptic sites increased GLT-1 diffusion, displacing transporters away from this compartment. Functionally, impairing GLT-1 membrane diffusion through cross-linking in vitro and in vivo slowed the kinetics of excitatory postsynaptic currents, indicative of a prolonged time course of synaptic glutamate. These data provide, to the best of our knowledge, the first evidence for a physiological role of GLT-1 surface diffusion in shaping synaptic transmission.

Lieu: Neurocentre Magendie Seminar room

Leonie Pothmann from the group of Prof. Heinz Beck (University of Bonn Medical Center) is giving a talk entitled 'Changes of inhibitory micronetworks in the epileptic hippocampus and their response to anticonvulsant drugs' on Wednesday, 15:00 in the Salle de conference of the Neurocentre.

CA1 microcircuits show profound reorganization in human and experimental temporal lobe epilepsy due to synaptic sprouting, loss of certain neuron types, and functional synaptic changes. The divers tasks of interneurons suggest, however, that morphological and behavioral alterations of surviving interneurons will also strongly influence network activity. The temporal activity pattern of a given interneuron is shaped by its synaptic inputs as well as its intrinsic properties. The spatial component of inhibition is determined by the axon morphology of different interneuron classes. Within CA1, a major source of excitatory input of interneurons is provided by local CA1 pyramidal cells, thereby creating a feedback inhibitory loop. We investigated whether the spatio-temporal profile of feedback inhibition in CA1 is changed in experimental epilepsy.

In the second part of my talk I will present data describing the effects of anticonvulsant drugs on the functioning of inhibitory microcircuits. The mechanisms of action of many CNS drugs have been studied extensively at the level of their target proteins, but the effects of these compounds at the level of complex CNS networks composed of different types of excitatory and inhibitory neurons are not well understood. Many currently used anticonvulsant drugs are known to exert potent use-dependent blocking effects on voltage-gated Na+ channels, thereby inhibiting pathological high-frequency firing. However, some GABAergic inhibitory neurons are capable of firing at very high rates, suggesting that these anticonvulsants should cause impaired GABAergic inhibition. We therefore studied the effects of different sodium channel blocking anticonvulsants on GABAergic inhibitory micro-networks in the rodent hippocampus of control and epileptic animals.

Pour plus de détails:

Feature produced in collaboration with Bertrand Nalpas, Research Director at Inserm and project manager Addiction - December 2014

Addictions are brain disease defined by an addiction to a substance or activity, with deleterious consequences. Researchers are trying to better describe the mechanisms involved in the development, maintenance and relapse of addiction. They also try to identify individual vulnerability factors, societal and environmental, for better prevention and care.

Article Neurosciences Bordeaux Neurocampus

Scribble1/AP2 Complex Coordinates NMDA Receptor Endocytic Recycling.
Piguel NH, Fievre S, Blanc JM, Carta M, Moreau MM, Moutin E, Pinheiro VL, Medina C, Ezan J, Lasvaux L, Loll F, Durand CM, Chang K, Petralia RS, Wenthold RJ, Stephenson FA, Vuillard L, Darbon H, Perroy J, Mulle C, Montcouquiol M, Racca C, Sans N. Cell Reports, Vol. 9, Issue 2, p712–727 Published online: October 9, 2014

Dans un travail publié en Octobre 2014 dans la revue Cell Reports, l’équipe “Polarite Planaire et Plasticite” dirigée par Mireille Montcouquiol et Nathalie Sans du Neurocentre Magendie (INSERM U862, Bordeaux) démontre le rôle clé des interactions entre la protéine de la polarité planaire Scribble1 et le complexe AP2 dans le maintien des récepteurs au glutamate de type NMDA au niveau des synapses.

General informations
Andreas Frick & al. in Nature Neuroscience

Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice. Andreas Frick et al. Nature Neuroscience published online 10 November 2014; doi:10.1038/nn.3864 (voir les commentaires d'Andreas Frick)

Please also find below several articles, press releases, and radio interviews about this work:
1. Site Bordeaux Neurocampus
2. revue de presse Inserm
3. Radio Campus, direct link to mp3
4. Pour La Science
5. Sud Ouest
6. Les Echos
7. Le Point

This work shows that the senses are impaired in children with this disease, but a molecule can reverse their behavior.

The team of Andreas Frick has identified the cause of sensory hypersensitivity that affects a large number of autistic and managed to fix it in the mouse.

Autism have difficulty integrating into their brain information from their senses, specificity handicaps in their daily lives.
The brain behind this anomaly remained mysterious until now. But researchers at INSERM, whose work has been published in the journal "Nature Neuroscience", seem to be able to solve this mystery by studying the brains of mice affected by a neurodevelopmental disease related to autism spectrum disorders, the "Fragile X syndrome". Neocortex rodents, the researchers found, is hyperexcited in response to tactile sensory stimulation.
This hyperexcitability neocortical, which influences how the neurons in this region of the brain include the sensory information is itself due to an alteration in the level of the entrance doors of the neurons that are the dendrites of certain ion channels through which pass bioelectric signals.
Using pharmacological molecule mimicking the functioning of these channels,
researchers could correct this hyperexcitability and the neocortical
abnormal neuronal integration.

Encoding of fear learning and memory in distributed neuronal circuits.Herry C, Johansen JP. Nat Neurosci. 2014 Dec;17(12):1644-1654. doi: 10.1038/nn.3869. Epub 2014 Nov 21. Review.Cyril Herry dans Nature neuroscience