from Montcouquiol-Sans's lab will defend her thesis entitled "Loss of Multiple PDZ domain containing protein has sensory and cognitive consequences"
Date de la soutenance: 12/12/2022 - 14h00
Lieu: Neurocentre Magendie Seminar room

Meeting room: salle nord (CGFB) & Zoom!

In this session, Claudia Fornari and Eloïse Daniel will talk to us about integrating Registered Reports into the grant funding process. They will be presenting the paper “Improving the Efficiency of Grant and Journal Peer Review: Registered Reports Funding” by Munafò

Claudia is a Ph.D. student on Beyeler’s team. She is working on the role of the insular cortex in the protective effect of progesterone in cocaine relapse.

Eloïse is a Ph.D. student on Montcouquiol/Sans’ Team. She works on the development and characterization of new experimental models to study the role of planar polarity signaling in memorization processes

from Montcouquiol-Sans's lab will defend her thesis entitled "Role of the planar polarity pathway in cognitive functions in the context of postnatal development and aging"

Centre Broca Nouvelle-Aquitaine

Thesis supervisor: Nathalie Sans

Defense in english
Date de la soutenance: 18/11/2022 - 14h00
Lieu: Centre Broca Nouvelle-Aquitaine

The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling.
Ana Dorrego-Rivas, Jerome Ezan, Maïté Moreau, Sonia Poirault-Chassac, Nathalie Aubailly, Julie De Neve, Camille Blanchard, Francis Castets, Amélie Fréal, Arne Battefeld, Nathalie Sans* & Mireille Montcouquiol*. Science Advances 8, eabo6333 (2022).

Over the years, our group has been exploring the many functions of Polarity and Planar Cell Polarity (PCP) proteins via cytoskeleton modulation on neurons. Members of these protein families play roles in important pathways that determine neural development and polarization of tissues. In this study, we found that Prickle2 (Pk2, OMIM 60850) is a neuronal polarity determinant and a new component of the axonal initial segment (AIS), participating in its early assembly and stabilization via direct binding to AnkG and microtubule bundling.

Many neurodevelopmental disorders (NDDs) are complex and multi-syndromic. Pathogenic protein variants associated with NDDs will affect the neuron, circuits and the entire brain, requiring multi-scale analysis to fully understand the underlying pathology. Our study shows that we should also consider the various compartments and sub-compartment of the neuron to fully understand the cellular consequences of NDDs.

Neurons are polarized cells with two defined compartments that differ in morphology and define neuronal function: the axonal and the somatodendritic domains. This asymmetry or polarity is crucial for proper neuronal signaling and communication. These neuronal compartments can be further divided into sub‐compartments that can be defined based on their morphology, molecular composition and/or function, such as the synaptic spines on dendrites, the presynaptic boutons in axon terminals, the proximal axon or AIS, and the distal axon.

Prickle 2, is a core PCP protein found initially at the synapse. Pathogenic variants in Prickle genes have been linked to NDDs such as spina bifida, autism spectrum disorders (ASD) and epilepsy. While defects in spines are believed to be at the roots of the pathologies, we unexpectedly found Pk2 at the AIS of neurons. The AIS not only coordinates the axo-dendritic polarity establishment and maintenance, it has its own plasticity that is an essential mechanism for tuning neuronal output and hence network coordination in response to changes in input.

We found Pk2 at very early developmental stages in the AIS suggesting that Pk2 may well be the first interactor of AnkyrinG-480 (AnkG), the AIS master organizer, helping AIS stabilization in the one neurite that will become the axon. The function of Pk2 in both the determination of the axon and the formation of the AIS is nicely illustrated when depleting Pk2 and creating a striking multiple axon phenotype with disrupted AIS(s). In addition, the axonal trafficking in these axon is affected (collaboration with Amelie Fréal, Vrije Universiteit, Amsterdam, Netherlands @FreAmeLie).

At least part of the deficits observed is due to the ability of Pk2 to potentiate a microtubule bundling activity of AnkG-480. But because the proteins interact via the ANK repeat of AnkG, common to all isoforms, they could also interact in spines. The consequences are important as the gene for AnkG, ANK3, are a critical gene in ASD, schizophrenia, bipolar disorder, intellectual disability (ID) and epileptic encephalopathy, and could therefore impact both compartments.

In collaboration with Arne Battefeld, the team leader of the team Pathophysiology of neuron-oligodendrocyte interactions at IMN from Bordeaux Neurocampus (https://www.bordeaux-neurocampus.fr/en/team/pathophysiology-of-neuron-oligodendrocyte-interactions/ @arne_feld) we show that Pk2-depleted neurons have lower excitability and lack sodium channel clustering at the AIS, a phenotype reminiscent of AnkG loss in Purkinje neurons.

Our results show that the presence of the same protein in multiple compartments, engaging in different protein complexes and signaling pathways has important consequence in pathology. When the protein is defective, due to a pathogenic variant of the gene, different compartments may be affected, complicating specific therapeutical approaches. This concept is critically important for complex pathologies like NDDs that still have poorly defined neuronal molecular signatures.

@PlanarPolarityT

Meeting room: Centre Broca

Program
9:00 – Jose A. ESTEBAN
Centro de Biología Molecular Severo Ochoa, Madrid
PI3K signaling for neuronal growth and synaptic plasticity

9:45 – Stéphane LÉON
Neurocentre Magendie (Cota Team)
Single-cell mapping of POMC neurons in obesity reveals novel subtypes with atypical identity

10:05 – Vincent PAGET-BLANC
IINS
A Synaptomic analysis reveals dopamine hub synapses in the mouse striatum

10:25-10:55 – Coffee break

10:55 – François LAMBERT
INCIA
Multimodal integration and plasticity in extraocular motoneurons: Synapse or phenotype matters?

11:25 – Ignacio FERNANDEZ MONCADA
Neurocentre Magendie (Marsicano Team)
CB1 receptors control memoryconsolidation via modulation of astroglial lactate and L-serine metabolism

11:45 – Agatha IDZIAK
IINS
It’s time for GreenT! A novel sensor for extracellular calcium imaging

12:05 – Cyril HANUS
Institute for Psychiatry and Neurosciences of Paris
N-glycans regulate synaptic receptor structure and function12:50-14:30 Lunch

12:50-14:30 – Lunch

14:30 – Anna BRACHET
IINS
Organization and role of beta spectrins in dendritic spines

15:00 – Lorena DELGADO
IMN
Normalization of substantia nigra pars reticulata parvalbumin-expressing neuron activity restores motor function in Parkinsonian mice

15:20 – Émilie PACARY
Neurocentre Magendie (Abrous Team)
The temporal origin of dentate granule neurons dictates their anatomical properties

15:50 – Nathan BENAC
IINS
Transient dopamine-NMDA receptor interaction governs hippocampal synaptic and network maturation

16:10 – Laura BALLERINI
SISSA, Trieste
Engineered nanomaterials to target synapses at the nanoscale

Scientific Committee
Elena AVIGNONE (Neurocentre Magendie)
Maurice GARRET (INCIA)
Mathieu LETELLIER (IINS)
Nathalie SANS (Neurocentre Magendie)

Registration
Please fill the registration formular by following the webpage down below:
https://framaforms.org/synapse-and-network-day-2022-1658751038

Félicitations aux lauréats magendiens !

CE13 – Biologie cellulaire, biologie du développement et de l’évolution
Catégorie PRC :

– MODCOM : Modulation de la communication trans- synaptique à la jonction neuromusculaire: des voies de signalisation aux approches thérapeutiques
Laure Strochlic (Institut de Myologie, Paris) / Nathalie Sans (Neurocentre Magendie), Jordi Molgo (CEA SIMOS_Paris) / Rozen LE PANSE (CRM_Paris)

CE14 – Physiologie et physiopathologie
Catégorie PRC :

– NeuroInflamIR – L’altération de l’homéostasie du glucose implique une nouvelle voie inflammatoire hypothalamique Mohammed Taouis (Institut des Neurosciences Paris-Saclay, Paris) / Daniela Cota (Magendie), Agnes Nadjar, (Magendie), Blandine Gatta-Cherifi (Magendie – CHU Bordeaux), Ariane Sharif (Lille Neurosciene & Cognition, Lille)

CE16 – Neurosciences moléculaires et cellulaires – Neurobiologie du développement

Catégorie JCJC (Jeunes Chercheuses et Jeunes Chercheurs) :

– AMY-FEB : Rôle des interneurones en panier et axo-axoniques de l’amygdale dans le contrôle de la
peur et de l’anxiété
Thomas Bienvenu (Magendie)

Catégorie PRC :

– GRINTRACK – Rôle de l’organisation à l’échelle nanométrique des récepteurs NMDA dans le développement normal du cerveau et les troubles GRIN.
Olivier Nicole (IINS) / Emilie Pacary (Magendie)

– PREGNENOID – Étude des mécanismes cellulaires et moléculaires qui constituent la boucle de régulation PREG-CB1R dans des conditions physiologiques et pathologiques
Monique Vallée (Magendie) / Luigi Bellocchio (Magendie)


CE37 – Neurosciences Intégratives et Cognitives

Catégorie PRC :

– CEA : Electrophysiologie des circuits de l’anxiété
Cyril Herry (Magendie), Anna Beyeler (Magendie), Thomas Bienvenu (Magendie), Thomas Tourdias (Magendie)

– EXINmemory : Etude du rôle des synapses excitatrices sur Interneurones dans le processus de mémoire
Yann Humeau (IINS), Daniel Choquet (IINS), Cyril Herry (Magendie)


CE45 – Interfaces: mathématiques, sciences du numérique – biologie, santé
Catégorie PRC :

– CROSS-TRACTS – Revealing the brain’s white matter crossing fibers’ topology: toward a new generation of tractography algorithms integrating the ground truth neuroanatomy.
Laurent Petit (IMN), Sylvain Miraux (CRMSB, Bordeaux), Andreas Frick (Magendie)

8 PhD students presented their doctoral research on Friday 17 June, during the second edition of the Bordeaux Neurocampus Doctoral Research Award Day.

Congratulations to the 4 laureates:

– Noemie Depret (Casden Prize) – Magendie (Montcouquiol-Sans)
– Zoé Grivet – IMN
– Catherine Marneffe – IINS
– Agata Nowacka – IINS

The second edition of this Day was really appreciated by the participants, the public and the jury. Congratulations to the 8 students, who all give a very good talk!

We thank the members of the jury (Jérôme Baufreton, Anna Brachet, Françoise Coussen, François Georges, Jean-Louis Guillou, Aude Panatier, Monique Vallée, Daniel Voisin and Laure Zago).

8 PhD students will be presenting their doctoral research on Friday 17 June.

Noémie DEPRET – Neurocentre Magendie
Thesis supervisor: Nathalie Sans
Title: Morphofunctional role of Vangl2 in the DG-CA3 circuit during postnatal development and aging