Retourner en haut

List Of News

2020-11-27 (STUDER Team) : "Cell Organ-izers”, a new IINS and Alvéole LabCom

The new Studer’s IINS team and the Alvéole company launch the CNRS joint laboratory "Cell Organ-izers".

Faced with the same issues/challenges for their academic research work or their clients, the IINS group led by Vincent Studer “Organ-izing the cell” and the Alvéole company have decided to create a common laboratory "Cell Organ-izers". It will aim at establishing a tight research partnership, likely to have a leverage effect in terms of both scientific production and innovation. The general theme of research of the JRL will be the development of  scale-up tools and methods to craft standardized human in vitro models for biology with the general goal of reconciliating the simplicity of in vitro models with complex properties encountered in vivo. We will focus our investigations on tools, methods and principles in straight line with Alveole’s product line, patent portfolio and target market. The results that we have obtained together within our previous collaboration contracts will be the starting bricks of the program. 

Contact: Vincent Studer

- See the Press release in French here
- See the Bordeaux Neurocampus website here
 

2020-11-19 (THOUMINE Team) : FluoSim, Matthieu Lagardère and Olivier Thoumine in Scientific Reports - November 2020

A simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins

We introduce fast, robust, and user-friendly software called FluoSim that allows for real time simulation of membrane protein dynamics in live-cell imaging and super-resolution modalities. We also show that FluoSim can be used to produce large virtual data sets for training deep neural networks for image reconstruction. This software should thus be of great interest to a wide community specialized in imaging methods applied to cell biology and neuroscience, with the common aim to better understand membrane dynamics and organization in cells. FluoSim is freely available on the website of the publisher Scientific Reports.

FluoSim: simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins
- Authors: Lagardère M, Chamma I, Bouilhol E, Nikolski M, Thoumine
- Scientific Reports 10, 19954 (2020). https://doi.org/10.1038/s41598-020-75814-y

+ See the movie here

Movie Legend:
Simulation of a Fluorescence Recovery After Photobleaching (FRAP) experiment.
The movie generated with FluoSim shows the distribution of surface receptors in a dendritic segment, with specific accumulation in post-synaptic areas (red color).
Receptors are photobleached at t = 5 sec in two specific synapses. Note the fluorescence recovery over time (total 60 sec), due to receptor diffusion and turnover.

2020-11-05 : IINS teams awarded a prestigious ERC Synergy 2020

The ENSEMBLE project aims at underpinning the molecular mechanisms of physiological and pathological brain function.

Congratulations to our ERC synergy 2020 awardees L. Groc, E. Bézard, V. Nägerl and L. Cognet!

We are happy and proud of this selection that will further expand our knowledge of the properties and function of the Brain extracellular space.

The teams of Laurent Groc (Research Director CNRS; Interdisciplinary Institute for Neuroscience), Erwan Bézard (Research Director Inserm; Institute of Neurodegenerative Disorders), Laurent Cognet (Research Director CNRS; Laboratoire photonique numérique et nanosciences) and Valentin Nägerl (Professor at University of Bordeaux; Interdisciplinary Institute for Neuroscience)  have been awarded the ERC Synergy Award 2020. The ENSEMBLE project aims at underpinning the molecular mechanisms of physiological and pathological brain function. This ambitious and innovative endeavor is based on their ability to develop new approaches in high-resolution microscopy at the service of a new conceptual framework in brain cell communication.

This project has roots in the international leadership of the Bordeaux community in the fields of microscopy, nanophotonics, fundamental and translational neuroscience. The opportunity that is offered to these 4 investigators to break a frontier knowledge was permitted by the continuous support of local institutional actors. The installation of Prof. Valentin Nägerl’s laboratory in 2009 with a "Chaire Accueil" from the Regional Council of Nouvelle-Aquitaine, the support of LabEx BRAIN, the Laphia Cluster and the IdEx of the University of Bordeaux provided the ground to build elementary blocks necessary for the challenging adventure of the ERC Synergy project (10 million euros, 6 years).

See the Bordeaux Neurocampus website 

2020-10-23 (TAKAHASHI Team) : Nature Neuroscience, October 2020 cover

Nature Neuroscience has selected the Naoya Takahashi's last paper 'Active dendritic currents gate descending cortical outputs in perception' for his October 2020 volume cover.

2020-10-22 (STUDER Team) : Microfabrication - Advanced Healthcare Materials, Oct. 2020

Physiologically relevant cell‐based models require engineered microenvironments

Physiologically relevant cell‐based models require engineered microenvironments which recapitulate the topographical, biochemical, and mechanical properties encountered in vivo. In this context, hydrogels are the materials of choice. Here a light based toolbox is able to craft such microniches out of common place materials. Extensive use of benzophenone photoinitiators and their interaction with oxygen achieves this. First, the oxygen inhibition of radicals is harnessed to photoprint hydrogel topographies. Then the chemical properties of benzophenone are exploited to crosslink and functionalize native hydrogels lacking photosensitive moieties. At last, photoscission is introduced: an oxygen driven, benzophenone‐enabled reaction that photoliquefies Matrigel and other common gels. Using these tools, soft hydrogel templates are tailored for cells to grow or self organize into standardized structures. The described workflow emerges as an effective microniche manufacturing toolset for 3D cell culture.

Authors: Aurélien Pasturel, Pierre‐Olivier Strale, Vincent Studer

- Advanced Healthcare Materials - First published: 02 August 2020 - https://doi.org/10.1002/adhm.202000519
- Contact: Vincent Studer

+ Thumbnail Leg. This spheroidally shaped cell culture of human embryonic kidney cells was templated by a photochemical technique. Vincent Studer and co-workers used photochemistry to controllably create hollow shapes within hydrogel structures. These hollows were then seeded with cells, which grew to fill the empty space. The spheroids were stained using a cell marker and the 3D imaging was accomplished with a bespoke digital micromirror-device-based confocal microscope.

2020-10-05 : Naoya Takahashi, laureate of the ATIP-Avenir 2020

Every year, as part of a partnership, Inserm and the French National Center for Scientific Research (CNRS) launch a call for proposals aimed at enabling young researchers to create and lead a team within an established Inserm or CNRS research center. The teams formed will work to strengthen the research of the host unit by independently developing their own research projects. This program aims to promote mobility and attract young, high-caliber team leaders.

Congratulations to Naoya Takahashi, IINS member, that is in the list of the selected candidates of the ATIP-Avenir - 2020!

Contact: Naoya Takahashi

2020-09-26 (NAGERL Team) : Nanoscale remodeling of astroglial processes - Neuron, Sept. 2020

LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia

LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia

Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections.

Authors: Christian Henneberger*, Lucie Bard*, Aude Panatier*, James P. Reynolds*, Olga Kopach*, Nikolay I. Medvedev*, Daniel Minge*, Michel K. Herde, Stefanie Anders, Igor Kraev, Janosch P. Heller, Sylvain Rama, Kaiyu Zheng, Thomas P. Jensen, Inmaculada Sanchez-Romero, Colin J. Jackson, Harald Janovjak, Ole Petter Ottersen, Erlend Arnulf Nagelhus, Stephane H.R. Oliet, Michael G. Stewart#, U. Valentin Nägerl#, Dmitri A. Rusakov#
* Co-first authors
, #Co-corresponding authors

This was a collaborative study with Christian Henneberger (Univ. of Bonn), Dmitri Rusakov (UCL) and Aude Panatier, Stéphane Oliet and Valentin Nägerl as partners in Bordeaux.

- Open Access Published: September 24, 2020 - DOI:https://doi.org/10.1016/j.neuron.2020.08.030
- Contact: Valentin Nägerl

2020-09-26 (CHOQUET Team) : Multicolor Spectrin labeling (ML Jobin)

This is a rat hippocampal neuron in culture stained with a series of markers

 

 

2020-09-22 : Synaptic plasticity and the recovery of altered skills

Cell Reports, Sept. 2020

AMPAR-Dependent Synaptic Plasticity Initiates Cortical Remapping and Adaptive Behaviors during Sensory Experience

Cortical plasticity improves behaviors and helps recover lost functions after injury. However, the underlying synaptic mechanisms remain unclear. In mice, we show that trimming all but one whisker enhances sensory responses from the spared whisker in the barrel cortex and occludes whisker-mediated synaptic potentiation (w-Pot) in vivo. In addition, whisker-dependent behaviors that are initially impaired by single-whisker experience (SWE) rapidly recover when associated cortical regions remap. Cross-linking the surface GluA2 subunit of AMPA receptors (AMPARs) suppresses the expression of w-Pot, presumably by blocking AMPAR surface diffusion, in mice with all whiskers intact, indicating that synaptic potentiation in vivo requires AMPAR trafficking. We use this approach to demonstrate that w-Pot is required for SWE-mediated strengthening of synaptic inputs and initiates the recovery of previously learned skills during the early phases of SWE. Taken together, our data reveal that w-Pot mediates cortical remapping and behavioral improvement upon partial sensory deafferentation.

Authors: Tiago Campelo, Elisabete Augusto, Nicolas Chenouard, Come Camus, Daniel Choquet, Frédéric Gambino

- Cell Reports, Sept. 2020 - DOI:https://doi.org/10.1016/j.celrep.2020.108097
- Contacts: Frédéric Gambino and Daniel Choquet

2020-09-21 (GROC Team) : NMDA receptor along dendrites - PNAS, September 2020

Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites

Hippocampal pyramidal neurons are characterized by a unique arborization subdivided in segregated dendritic domains receiving distinct excitatory synaptic inputs with specific properties and plasticity rules that shape their respective contributions to synaptic integration and action potential firing. Although the basal regulation and plastic range of proximal and distal synapses are known to be different, the composition and nanoscale organization of key synaptic proteins at these inputs remains largely elusive. Here we used superresolution imaging and single nanoparticle tracking in rat hippocampal neurons to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDA receptors (NMDARs) -which play key roles in the use-dependent adaptation of glutamatergic synapses- along the dendritic arbor. We report significant changes in the nanoscale organization of GluN2B-NMDARs between proximal and distal dendritic segments, whereas the topography of GluN2A-NMDARs remains similar along the dendritic tree. Remarkably, the nanoscale organization of GluN2B-NMDARs at proximal segments depends on their interaction with calcium/calmodulin-dependent protein kinase II (CaMKII), which is not the case at distal segments. Collectively, our data reveal that the nanoscale organization of NMDARs changes along dendritic segments in a subtype-specific manner and is shaped by the interplay with CaMKII at proximal dendritic segments, shedding light on our understanding of the functional diversity of hippocampal glutamatergic synapses.

Authors: Joana S. Ferreira, Julien P. Dupuis, Blanka Kellermayer, Nathan Bénac, Constance Manso, Delphine Bouchet, Florian Levet, Corey Butler, Jean-Baptiste Sibarita, and Laurent Groc

2020-09-01 (ELEGHEERT Team) : Synthetic excitatory synaptic organizer - Science, August 2020

Science, August 2020

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

The human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer’s disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits.

Authors: Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, Wataru Kakegawa, Amber J. Clayton, Veronica T. Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A. Radu Aricescu, Michisuke Yuzaki

- Science, 28 Aug 2020: Vol. 369, Issue 6507, eabb4853 - DOI: 10.1126/science.abb4853
- Contact: Jonathan Elegheert

2020-07-30 (GIANNONE Team) : Deciphering mechano-biology using super-resolution microscopy

Nature Cell Biology, July 2020

Cell stretching is amplified by active actin remodeling to deform and recruit proteins in mechano-sensitive structures Detection and conversion of mechanical forces into biochemical signals control cell functions during physiological and pathological processes. Mechano-sensing is based on protein deformations and reorganizations, yet the molecular mechanisms are still unclear. Using a cell stretching device compatible with super-resolution microscopy (SRM) and single protein tracking (SPT), we explored the nanoscale deformations and reorganizations of individual proteins inside mechano-sensitive structures. We achieved SRM after live stretching on intermediate filaments, microtubules and integrin adhesions. Simultaneous SPT and stretching showed that while integrins follow the elastic deformation of the substrate, actin filaments and talin also displayed lagged and transient inelastic responses associated with active acto-myosin remodeling and talin deformations. Capturing acute reorganizations of single-molecule during stretching showed that force-dependent vinculin recruitment is delayed and depends on the maturation of integrin adhesions. Thus, cells respond to external forces by amplifying transiently and locally cytoskeleton displacements enabling protein deformation and recruitment in mechano-sensitive structures.

Authors: Sophie Massou*, Filipe Nunes Vicente*, Franziska Wetzel*, Amine Mehidi, Dan Strehle, Cecile Leduc, Raphaël Voituriez, Olivier Rossier, Pierre, Nassoy and Gregory Giannone
* First co-authors

- Nature Cell Biology, DOI 10.1038/s41556-020-0548-2.
- Contacts IINS: Grégory Giannone and Filipe Nunes Vicente

+ Cf. INSB website (French) here
+ Cf. Bordeaux Neurocampus website here

2020-07-20 : A new website for the Aquitaine Delegation of the CNRS

None

On the new Aquitaine Delegation website find dedicated pages to the organization of the Delegation, scientific potential, innovation, as well as an agenda and a News section here

2020-07-10 (MULLE Team) : Presynaptic failure in Alzheimer’s disease

Progress in Neurobiology, May 2020

Synaptic loss is the best correlate of cognitive deficits in Alzheimer’s disease (AD). Extensive experimental evidence also indicates alterations of synaptic properties at the early stages of disease progression, before synapse loss and neuronal degeneration. A majority of studies in mouse models of AD have focused on post-synaptic mechanisms, including impairment of long-term plasticity, spine structure and glutamate receptor-mediated transmission. Here we review the literature indicating that the synaptic pathology in AD includes a strong presynaptic component. We describe the evidence indicating presynaptic physiological functions of the major molecular players in AD. These include the amyloid precursor protein (APP) and the two presenilin (PS) paralogs PS1 or PS2, genetically linked to the early-onset form of AD, in addition to tau which accumulates in a pathological form in the AD brain. Three main mechanisms participating in presynaptic functions are highlighted. APP fragments bind to presynaptic receptors (e.g. nAChRs and GABAB receptors), presenilins control Ca2+ homeostasis and Ca2+-sensors, and tau regulates the localization of presynaptic molecules and synaptic vesicles. We then discuss how impairment of these presynaptic physiological functions can explain or forecast the hallmarks of synaptic impairment and associated dysfunction of neuronal circuits in AD. Beyond the physiological roles of the AD-related proteins, studies in AD brains also support preferential presynaptic alteration. This review features presynaptic failure as a strong component of pathological mechanisms in AD.


- Progress in Neurobiology 2020 - doi:10.1016/j.pneurobio.2020.101801
- Authors and contacts: Gaël Barthet and Christophe Mulle

+ Cf Bordeaux Neurocampus website here

2020-07-01 (GROC Team) : Retrovirus, inflammation and psychosis: a missing link identified!

Science Advances, July 2020

Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis 

Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral origin alter brain cell communication remain poorly understood. Here, we combined single-molecule tracking, calcium imaging, and behavioral approaches to demonstrate that the envelope protein (Env) of HERV type W, which is normally silenced but expressed in patients with neuropsychiatric conditions, alters the N-methyl-d-aspartate receptor (NMDAR)–mediated synaptic organization and plasticity through glia- and cytokine-dependent changes. Env expression in the developing hippocampus was sufficient to induce behavioral impairments at the adult stage that were prevented by Env neutralization or tuning of NMDAR trafficking. Thus, we show that a HERV gene product alters glutamate synapse maturation and generates behavioral deficits, further supporting the possible etiological interplay between genetic, immune, and synaptic factors in psychosis.

Authors: E.M. Johansson, D. Bouchet, R. Tamouza, P. Ellul, AS. Morr, E. Avignone, R. Germi, M. Leboyer, H. Perron and L. Groc

- Science Advances 17 Jul 2020: Vol. 6, no. 29, eabc0708 - DOI: 10.1126/sciadv.abc0708
- Contacts: Emily M. Johannson and Laurent Groc
+ More details on the Neurocampus website here

2020-06-28 (CHOQUET Team) : AMPA receptor nanoscale dynamic organization and synaptic plasticities

Current Opinion in Neurobiology, August 2020

Review on “AMPA receptor nanoscale dynamic organization and synaptic plasticities” in Current Opinion in Neurobiology 2020

The emergence of new imaging techniques and molecular tools has refreshed our understanding of the principles of synaptic transmission and plasticity. Superresolution imaging and biosensors for measuring enzymatic activities in live neurons or neurotransmitter levels in the synaptic cleft are giving us an unprecedented integrated and nanoscale view on synaptic function. Excitatory synapses are now conceptualized as organized in subdomains, enriched with specific scaffolding proteins and glutamate receptors, molecularly organized with respect to the pre-synaptic source of glutamate.

This new vision of basic synaptic transmission changes our understanding of the molecular modifications which sustain synaptic plasticities. Long-term potentiation can no longer be explained simply by an increase in receptor content at the synapse. We review here the latest data on the role of nanoscale and dynamic organization of AMPA type glutamate receptors on synaptic transmission at both basal state and during short and long-term plasticities.

- Current Opinion in Neurobiology - Volume 63, August 2020, Pages 137-145 https://doi.org/10.1016/j.conb.2020.04.003
- Contacts: Daniel Choquet and Eric Hosy

2020-06-08 (CHOQUET Team) : Co-organization and coactivation of AMPAR, NMDAR, and mGluR

PNAS, June 2020

Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses.

The nanoscale co-organization of neurotransmitter receptors facing presynaptic release sites is a fundamental determinant of their coactivation and of synaptic physiology. At excitatory synapses, how endogenous AMPARs, NMDARs, and mGluRs are co-organized inside the synapse and their respective activation during glutamate release are still unclear. Combining single-molecule super resolution microscopy, electrophysiology, and modeling, we determined the average quantity of each glutamate receptor type, their nanoscale organization, and their respective activation. We observed that NMDARs form a unique cluster mainly at the center of the PSD, while AMPARs segregate in clusters surrounding the NMDARs.mGluR5 presents a different organization and is homogenously dispersed at the synaptic surface. From these results, we build a model predicting the synaptic transmission properties of a unitary synapse, allowing better understanding of synaptic physiology.

Authors: Julia Goncalves, Tomas M. Bartol, Côme Camus, Florian Levet, Ana Paula Menegolla,Terrence J. Sejnowski, Jean-Baptiste Sibarita, Michel Vivaudou, Daniel Choquet and Eric Hosy

- Publication in PNAS, June 8, 2020 https://doi.org/10.1073/pnas.1922563117
- Contact: Eric Hosy

+ Cf Bordeaux Neurocampus website here

2020-06-08 : Receptor mobility under the spotlight

Science, June 2020

Linking glutamate receptor movements and synapse function
Regulation of neurotransmitter receptor content at synapses is achieved through a dynamic equilibrium between biogenesis and degradation pathways, receptor stabilization at synaptic sites, and receptor trafficking in and out synapses. In the past 20 years, the movements of receptors to and from synapses have emerged as a series of highly regulated processes that mediate postsynaptic plasticity. Our understanding of the properties and roles of receptor movements has benefited from technological advances in receptor labeling and tracking capacities, as well as from new methods to interfere with their movements. Focusing on two key glutamatergic receptors, we review here our latest understanding of the characteristics of receptor movements and their role in tuning the efficacy of synaptic transmission in health and brain disease.

Authors: Laurent Groc and Daniel Choquet

- Review Science 368, eaay4631, June 2020 - Doi: 10.1126/ science.aay4631
- Contacts: Laurent Groc, Daniel Choquet

+ Cf. PDF version.
+ Cf Bordeaux Neurocampus website here
+ Cf. INSB info-press (in French), here

2020-05-28 (PERRAIS Team) : MemTraS: A new team at IINS

MemTraS - Membrane traffic at synapses

"MemTraS - Membrane traffic at synapses" is a new team recently born at IINS. The leader, David Perrais, presents the research axis:
Our goal in the team is to study the mechanisms of synapse function. We focus on membrane trafficking events, exocytosis and endocytosis, in normal brain physiology or in the course of disease. Indeed, membrane trafficking is essential in both sides of the synapse. The presynaptic element is filled with synaptic vesicles which fuse at the active zone to release neurotransmitter molecules, one of the defining features of synaptic transmission. After fusion, vesicles are very quickly and efficiently recycled to cope with neuronal activity. At the post-synaptic side, post-synaptic receptors are going through cycles of endocytosis and recycling, which is essential to regulate synaptic transmission and plasticity. We want to analyse how these processes are organized in space and time. Finally, we are not only interested in canonical synapses, such as cortical glutamatergic synapses, but also in rare and much less understood synapse populations such as neuromodulatory dopamine synapses.

To tackle these issues, we combine two types of expertise mastered by the researchers of the team, myself and Etienne Herzog. I bring electrophysiology combined with the most advanced fluorescence imaging techniques to detect and characterize individual exocytosis and endocytosis events in living cells, while Etienne brings his method of purification of synaptosomes from adult animals with fluorescence activated synaptosome sorting which enables powerful proteomics, transcriptomics and functional approaches. Altogether we aim at identifying new principles of organization in specific synapses and test their relevance for synaptic function in the normal and diseased brain.

The members of the team being formed in January 2020 are Lou Bouit, Silvia Sposini, Marlene Pfeffer, Etienne Herzog, May Bakr and David Perrais.

- More details on the Bordeaux Neurocampus website here.
- Contact: David Perrais

2020-04-29 (THOUMINE Team) : Controlling synapse differentiation with light - eLife, April 2020

eLife, April 2020

Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation.
Neuroligins (Nlgns) are adhesion proteins mediating trans-synaptic contacts in neurons. However, conflicting results around their role in synaptic differentiation arise from the various techniques used to manipulate Nlgn expression level. Orthogonally to these approaches, we triggered here the phosphorylation of endogenous Nlgn1 in CA1 mouse hippocampal neurons using a photoactivatable tyrosine kinase receptor (optoFGFR1). Light stimulation for 24 hr selectively increased dendritic spine density and AMPA-receptor-mediated EPSCs in wild-type neurons, but not in Nlgn1 knock-out neurons or when endogenous Nlgn1 was replaced by a non-phosphorylatable mutant (Y782F). Moreover, light stimulation of optoFGFR1 partially occluded LTP in a Nlgn1-dependent manner. Combined with computer simulations, our data support a model by which Nlgn1 tyrosine phosphorylation promotes the assembly of an excitatory post-synaptic scaffold that captures surface AMPA receptors. This optogenetic strategy highlights the impact of Nlgn1 intracellular signaling in synaptic differentiation and potentiation, while enabling an acute control of these mechanisms.

Authors: Letellier M, Lagardère M, Tessier B, Janovjak H, Thoumine O.

- Publication on Elife. 2020 Apr 23;9. pii: e52027. doi: 10.7554/eLife.52027.
- Contacts: Mathieu Letellier and Olivier Thoumine
+ Cf Bordeaux Neurocampus website here

2020-04-23 (NAGERL Team) : Astrocytes: up close & personal via STED microscopy

Nature Communications, April 2020

Structural basis of astrocytic Ca2+ signals at tripartite synapses
Astrocytic Ca2+ signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca2+ imaging showed that nodes were biochemical compartments and Ca2+ microdomains. Mapping astrocytic Ca2+ signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on living nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes.

The study (Arizono et al, Nature Communications 2020), which was spearheaded by Misa Arizono in the Nägerl team, was supported by a long-standing and fruitful collaboration with the Bordeaux Neurocampus teams of Marsicano and Oliet, which received funding from the Labex Brain and ANR.

Authors: Misa Arizono, V. V. G. Krishna Inavalli, Aude Panatier, Thomas Pfeiffer, Julie Angibaud, Florian Levet, Mirelle J. T. Ter Veer, Jillian Stobart, Luigi Bellocchio, Katsuhiko Mikoshiba, Giovanni Marsicano, Bruno Weber, Stéphane H. R. Oliet & U. Valentin Nägerl

- See the publication on Nature Communications volume 11, Article number: 1906 (2020) https://www.nature.com/articles/s41467-020-15648-4
- Contact: Valentin Nägerl, IINS

2020-04-16 (NAGERL Team) : Salivary Gland Surveillance - Science Immunology, April 2020

Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance
Pathogen sensing in tissues is critical to generating rapid immune responses. Within these tissues, macrophages and resident memory CD8+ T cells (TRM) work together to detect pathogens, and Stolp et al. use intravital imaging of submandibular salivary glands (SMG) to show that TRM follow tissue macrophage topology in a dynamic manner. Macrophage depletion is associated with reduced TRM motility and a diminished clustering in response to inflammatory chemokines. However, although SMG TRM respond to chemoattractants, autonomous motility is also observed and is mediated by friction and insertion of cellular protrusions into microenvironmental gaps. These findings demonstrate that SMG TRM can use different motility modes in proximity to tissue macrophages to patrol the tissue microenvironment.

Authors: Bettina Stolp, Flavian Thelen, Xenia Ficht, Lukas M. Altenburger, Nora Ruef, V. V. G. Krishna Inavalli, Philipp Germann, Nicolas Page, Federica Moalli, Andrea Raimondi, Kirsten A. Keyser, S. Morteza Seyed Jafari, Francesca Barone, Matthias S. Dettmer, Doron Merkler, Matteo Iannacone, James Sharpe, Christoph Schlapbach, Oliver T. Fackler, U. Valentin Nägerl and Jens V. Stein

- See the publication on Science Immunology 03 Apr 2020: Vol. 5, Issue 46, eaaz4371 - DOI: 10.1126/sciimmunol.aaz4371
- Contact: Valentin Nägerl, IINS

2020-04-07 : Information : Coronavirus

None

The French Academy of Sciences provides links to find reliable information on the COVID-19 Coronavirus epidemic.

2020-04-06 : New member

New member at the cell biology core facility

A newcomer recently joined our team. Audrey Lacquemant is now working in the cell biology facility. Welcome to her!

2020-03-16 : IINS is temporarily closed

None

Our lab has closed down to allow the personnel to go under confinement and protection. A handful of dedicated members is taking care of our precious biological samples and mouse colonies. 

2019-12-05 (CHOQUET Team) : A discrete presynaptic vesicle cycle for neuromodulator receptors - Neuron, December 2019

A major function of GPCRs is to inhibit presynaptic neurotransmitter release, requiring ligand-activated receptors to couple locally to effectors at terminals. The current understanding of how this is achieved is through receptor immobilization on the terminal surface. Here, we show that opioid peptide receptors, GPCRs that mediate highly sensitive presynaptic inhibition, are instead dynamic in axons. Opioid receptors diffuse rapidly throughout the axon surface and internalize after ligand-induced activation specifically at presynaptic terminals. We delineate a parallel regulated endocytic cycle for GPCRs operating at the presynapse, separately from the synaptic vesicle cycle, which clears activated receptors from the surface of terminals and locally reinserts them to maintain the diffusible surface pool. We propose an alternate strategy for achieving local control of presynaptic effectors that, opposite to using receptor immobilization and enforced proximity, is based on lateral mobility of receptors and leverages the inherent allostery of GPCR-effector coupling.

Damien Jullié, Miriam Stoeber, Jean-Baptiste Sibarita, Hanna L. Zieger, Thomas M. Bartol, Seksiri Arttamangkul, Terrence J. Sejnowski, Eric Hosy, and Mark von Zastrow

- Neuron. 2019 Dec 5 - doi: 10.1016/j.neuron.2019.11.016.
- Contact: Eric Hosy