Muriel Koehl, Inserm researcher in Nora Abrous’ team (Neurocentre Magendie), has obtained a JTC (Joint Transnational Calls) funding for a project with two European partners.

Nora Abrous & Emilie Pacary are also involved in the project

Partners:

– Parkitna Jan Rodriguez, Department of Molecular Neuropharmacology, Maj Institute of Pharmacology of the Polish Academy of Sciences, Krakow, Poland

– Hayder Amin, Biohybrid Neuroelectronics Group, German Center for Neurodegenerative Diseases, Dresden, Germany

PROJECT : ResiPreS (Neurobiological basis of resilience/vulnerability to prenatal stress in mice)
When mothers experience stress during pregnancy, known as prenatal stress (PS), it may increase their offspring’s risk of developing stress-induced mental diseases such as anxiety, depression, or post-traumatic stress disorder (PTSD). However, not everyone develops this pathological behavior after stress exposure, pointing to the existence of resilience factors that need exploration. We found that PS in mice is associated with behavioral disturbances such as PTSD-like memory issues or depression-like behavior in some, but not all individuals. This discrepancy mimics human behavior, making it a valuable model for understanding the mechanisms underlying resilience / vulnerability to stress.

Our mechanistic target is a brain region called the dentate gyrus of the hippocampus, which is crucial for emotional memory control and is characterized by a continuous neurogenic development, leading to the existence of temporally distinct neuronal populations. Our hypothesis is that these distinct neuronal populations may present different responsiveness to PS, thus leading to the establishment of the individual’s resilience or vulnerability to stress.

Using cutting-edge techniques, our aim is thus to investigate these neurons’ anatomo-functional properties, their gene expression patterns, and their contribution to hippocampal network activity. Once we have identified specific cells or genes involved, we will test their direct impact in resilience /vulnerability to stress.

Overall, by studying the mechanisms that decide why some people develop stress-induced pathologies and others do not, we hope to highlight new therapeutic targets and better, more effective, treatments for conditions that develop in individuals exposed to deleterious life events.

Source

https://www.neuron-eranet.eu/projects/ResiPreS/

Meeting room: Centre Broca Nouvelle-Aquitaine

from Columbia University, New York, USA's lab will give a presentation entitled 'Adult Hippocampal neurogenesis, pattern separation, and overgeneralization'

René HEN
Columbia University, New York, USA

Invited by Nicolas Blin (Abrous’ Lab – Magendie)

Title
Adult Hippocampal neurogenesis, pattern separation, and overgeneralization

Abstract
Adult born granule cells (abGCs) have been implicated in memory discrimination through a neural computation known as pattern separation. We have examined how chronic ablation or acute chemogenetic silencing of abGCs affects the activity of mature granule cells (mGCs) using in vivo Ca2+ imaging. In both cases we observed altered remapping of mGCs. Rather than broadly modulating the activity of all mGCs, abGCs promote the remapping of place cells’ firing fields while increasing rate remapping of mGCs representing sensory cues. In turn, these remapping deficits are associated with behavioral impairments in animals’ ability to correctly identify new goal locations. Thus, abGCs facilitate pattern separation through the formation of non-overlapping representations for identical sensory cues encountered in different locations. In the absence of abGCs the dentate gyrus shifts to a state dominated by cue information, a situation that is consistent with the overgeneralization often observed in anxiety or age related disorders.

Publications
Tuncdemir SN, Grosmark AD, Chung H, Luna VM, Lacefield CO, Losonczy A, and Hen R. Adult born granule cells facilitate remapping of spatial and non-spatial representations in the dentate gyrus. 2023, Neuron. In press (online, Oct 10).

Stefanini F, Kushnir L, Jimenez JC, Jennings JH, Woods NI, Stuber GD, Kheirbek MA, Hen R, Fusi S. (2020) A Distributed Neural Code in the Dentate Gyrus and in CA1. Neuron.107(4):703-716.

Luna VM, Anacker C, Burghardt N, Khandaker H, Andreu V, Millette A, Leary P,
Ravenelle R, Jimenez J, Mastrodonato A, Denny CA, Fenton A, Scharfman H, Hen R. (2019); Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus. Science. 364(6440):578-583.

from Abrous's lab will defend his thesis entitled 'Role of adult-born dentate neurons in the resilience to cognitive aging'


Thursday 14 December / 09:30
Venue: Centre Broca

Defense in english

Nicolas Blin
Inserm
Team: Neurogenesis and pathophysiology (Magendie)
Thesis supervisor: Nora Abrous

Title
Role of adult-born dentate neurons in the resilience to cognitive aging

Jury
Pf. René Hen – Columbia University – New York City
Pf. Sandrine Thuret – King’s College – London
Dr. Luisa V. Lopez – Lisbon University – Lisbon
Dr. Luisa Pinto – Minho University – Minho
Dr. Nora Abrous – Université de Bordeaux – Bordeaux (Directrice de thèse)
Dr. Vanessa Charrier – Université de Bordeaux – Bordeaux (Membre invité – Co-superviseure)

Publications
1. The temporal origin of dentate granule neurons dictates their role in spatial memory – Molecular Psychiatry 2021 (26, 7130–7140, 2021) Masachs N*, Charrier V*, Farrugia F, Lemaire V, Blin N, Mazier W, Tronel S, Montaron MF, Ge S, Marsicano G, Cota D, Deroche-Gamonet V, Herry C, Abrous DN.

2. Responsiveness of dentate neurons generated throughout adult life is associated with resilience to cognitive aging – Aging Cell 2020 (Aug;19(8):e13161) Montaron MF*, Charrier V*, Blin N, Garcia P, Abrous DN.
Date de la soutenance: 14/12/2023 - 09h30
Lieu: Centre Broca

from Abrous team will defend his thesis entitled 'Involvement of adult hippocampal neurogenesis and prenatal stress in vulnerability to develop memory disturbances associated with post-traumatic stress disorder in a mouse model'

Soutenance en français

Mohamed-Lyès Kaci
Neurocentre Magendie
Equipe : Neurogénèse et physiopathologie
Thèse dirigée : Muriel Koehl

Titre
Implication de la neurogenèse hippocampique adulte et du stress prénatal dans la vulnérabilité à développer des altérations mnésiques associées au trouble de stress post-traumatique dans un modèle murin

Résumé
Le trouble de stress post-traumatique (TSPT) est une pathologie neuropsychiatrique qui peut survenir suite à une expérience traumatisante. Contrairement à la perception courante qui associe le TSPT à une intensification excessive du souvenir traumatique, les patients manifestent en réalité un profil mnésique particulier. D’un côté, ils présentent en effet une hypermnésie émotionnelle pour certains détails sensoriels de l’événement, et de l’autre, une amnésie déclarative pour le contexte entourant cet événement. Ce profil mnésique semble central dans la pathologie, et des études récentes suggèrent que la déficience contextuelle pourrait être au cœur de la mémoire traumatique. Toutefois, les mécanismes neurobiologiques sous-jacents demeurent largement inexplorés.

Les neurones générés dans l’hippocampe au cours du processus de neurogenèse adulte (Neurogenèse Hippocampique Adulte, NHA) jouent un rôle essentiel dans la mémoire contextuelle, la séparation de pattern et la résilience au stress. Ces fonctions suggèrent un rôle potentiel de ces neurones dans les altérations mnésiques caractéristiques du TSPT. Nous avons donc tout d’abord testé l’hypothèse selon laquelle l’activité de ces neurones nouvellement formés était impliquée dans la formation de la mémoire traumatique. En combinant des techniques d’optogénétique avec un modèle murin permettant de distinguer le développement d’une mémoire de peur normale et adaptative de celui d’une mémoire de peur pathologique de type TSPT, nous avons démontré que l’activation ou l’inhibition de ces neurones prévenait ou induisait respectivement le développement d’une mémoire de type TSPT.

Chez l’humain, tous les individus exposés à des événements traumatiques ne développent pas de TSPT soulignant l’existence de facteurs de risque. Les expériences de vie précoce, y compris celles vécues in utero, ont une influence à long-terme sur le développement et les fonctions cérébrales. En particulier, il a été suggéré que le stress précoce pourrait augmenter la vulnérabilité à développer certaines pathologies neuropsychiatriques, mais les mécanismes sous-tendant cette vulnérabilité restent méconnus. De manière intéressante, l’exposition à un stress prénatal réduit la NHA chez la souris. Compte tenu de ces données et de nos découvertes sur le rôle de la NHA dans la mémoire traumatique, nous avons postulé d’une part que le stress prénatal pourrait augmenter la susceptibilité à développer une mémoire traumatique, et d’autre part que la NHA était impliquée dans cette vulnérabilité. Nous avons tout d’abord confirmé la présence d’altérations comportementales liées à des fonctions sous-tendues par la NHA chez des souris ayant subi un stress prénatal, en utilisant deux tâches comportementales de séparation de pattern. Par la suite, en utilisant notre modèle de mémoire traumatique, nous avons observé que ces souris présentaient un profil mnésique typique du TSPT, et que l’activation optogénétique des neurones issus de la NHA pouvait prévenir l’apparition de ce profil au profit d’une mémoire de peur normale et adaptative.

En conclusion, ce travail de thèse met en évidence le rôle crucial des neurones hippocampiques générés à l’âge adulte dans la mémoire traumatique, et suggère qu’une altération de ce processus neurobiologique pourrait expliquer la vulnérabilité induite par le stress prénatal, ouvrant ainsi de nouvelles voies préventives et thérapeutiques pour le TSPT.

Mots clés
Neurogenèse adulte, TSPT, mémoire de peur, stress prénatal, hippocampe, comportement

Jury
Patricia Gaspar,
René Hen,
Catherine Belzung,
Guillaume Ferreira,
Pierre Gagnepain,
Muriel Koehl (directrice de thèse)
Aline Desmedt (invitée)
Nora Abrous (invitée)
Date de la soutenance: 13/12/2023 - 14h00
Lieu: Centre Broca

e Precision and global vascular brain health institute (VBHI) project, coordinated by the University of Bordeaux and supported by the Bordeaux University Hospital, Inserm, Inria and the Nouvelle-Aquitaine Region, is the winner of the France 2030 plan's call for UHI 3 projects.

This new University Hospital Institute, directed by Stéphanie Debette, professor at the University and CHU of Bordeaux and director of the Bordeaux Population Health research centre (University of Bordeaux, Inserm), will be dedicated to brain vascular health.

The aim will be to develop a new paradigm integrating population health and therapeutic innovation to combat the most common neurological diseases, strokes and dementia, and to promote good brain aging. This new Institute will be at the heart of an emerging global dynamic focused on innovation and inclusion, aiming to maximise the scientific, medical and socio-economic impact of cerebrovascular health research, at national and international levels.

Several researchers from Bordeaux Neurocampus, some⋅e⋅s being also hospital staff in CHU departments or units (in neurology, neuroimaging or neurogenetics) are involved in this IHU:
- At the Neurocentre Magendie: Thomas Tourdias, Vincent Dousset, Nora Abrous ;
- At the IMN: Fabien Wagner, Michel Thiébaut de Schotten, Arne Battefeld, Wassilios Meissner;
- At INCIA: Igor Sibon, Bruno Bontempi and Jean-Luc Morel, Cyril Goizet, Nathalie Salles;
- At IINS: Laurent Groc

In Nouvelle-Aquitaine, there is a life beside research! Through short video portraits, we discover these unknown facets of scientists: their passion for painting, climbing or a collection of beetles. They are neuroscientists, chemists or geneticists in Inserm units. The DR Nouvelle-Aquitaine is launching a series of portraits featuring all of these women and men of science.

Nora Abrous is head of the Neurogenesis and Pathophysiology team at the Neurocentre Magendie/Inserm UMR 1215 in Bordeaux.

Meeting room: Centre Broca Nouvelle-Aquitaine

Organizers:
Pr Muriel Darnaudery (NutriNeuro) / Dr Muriel Koehl (Magendie / Eq Abrous)

Registration
Free but mandatory
https://framaforms.org/registration-early-life-adversity-and-mental-health-october-19th-1654782881


Program
9h – 12h30 : Early life adversities/environment and health
9h00 – VINCENT PREVOT (Lille, France)
GnRH neurons sculpt their neuroglial environment in infancy to enable proper sexual maturation and fertility

9h30 – MEGGANE MELCHIOR (Strasbourg, France.)
Early life environment and its impact on pain responses

10h00 – MOHAMED-LYES KACI (Bordeaux France)
Early programming of psychopathologies by Prenatal stress

10h30 – COFFEE BREAK

11h00 – CEDRIC GALERA (Bordeaux, France)
Cord Serum Cytokines at Birth and Children’s Anxiety-Depression Trajectories From 3 to 8 Years: The EDEN Mother–Child Cohort

11h30 – ARNAUD TANTI (Tours, France)
Investigating the cellular and molecular effects of child abuse in the post-mortem brain: from myelination to the remodeling of the extracellular matrix

– LUNCH ON YOUR OWN –

14h – 17h : How does early life stress get under the skin ?
14h00 – MICHELLE KELLY-IRVING (Toulouse, France)
Adverse childhood experiences and health in adulthood in a British birth cohort study: critical considerations on life course mechanisms

14h30 – ANNA-MARIA CATTANEO (Brescia Italy; London, UK)
Early exposure to environmental insults: focus on biological pathways and epigenetic mechanisms

15h00 – COFFEE BREAK

15h30 -PATRICIA GASPAR (Paris, France)
Common features of early life stress and antidepressant (SSRI) administration on the development of prefrontal circuits

16h00 – HELEN E VUONG (University Of Minnesota, USA)
Interactions between the microbiome and central nervous system: implications for neurodevelopment and behavior.

16h30 – Keynote lecture – CATHERINE JENSEN PEÑA (Princeton Neuroscience Institute, USA)
Early life stress primes sensitivity to future stress: from engrams to epigenetics


Contact
Muriel Darnaudery : muriel.darnaudéry@u-bordeaux.fr
Muriel Koehl : muriel.koehl@inserm.fr

Funded by Bordeaux Neurocampus
Société française de neuroendocrinologie