Team
REMEMBeR
Team manager: Rampon Claire
Presentation
Our team is interested in brain plasticity phenomena related to spatial and episodic memory in healthy mice or in models of pathology associated with memory dysfunctions. The aim of our research is to identify the plasticity processes induced by learning by studying them at different levels of brain function, ranging from the activity of neuronal networks (brain oscillations, synaptic plasticity, inhibitory functions) to cellular analysis (neurogenesis, neuronal morphology, neuron-glial cell interactions), biochemical (protein expression, neurotransmitter release, role of mitochondria) and molecular (epigenetic regulation, role of transcription factors). We are also studying these brain mechanisms in the context of Alzheimer’s disease, mood disorders and post-traumatic stress. Using mouse models of these diseases, we are also conducting projects aimed at assessing the therapeutic value of pharmacological or behavioral strategies.
Project 1
Alzheimer’s disease (AD) is the most common form of dementia in the elderly and is characterized by an inexorable loss of memory as well as other cognitive functions. Our team focuses on the mechanisms responsible for memory loss in AD. Using transgenic mouse models of AD, we study how the pathology affects hippocampal plasticity, from the network level down to the cellular level, with particular attention to forms of plasticity that are preserved despite the disease. We are also testing new behavioral and pharmacological approaches aimed at improving memory functions in AD-affected mice.
Our current projects are more specifically focused on:
– The mechanisms underlying physical activity-mediated attenuation of cognitive decline in Alzheimer’s disease (Claire Rampon, Fanny Rayssiguier, Sébastien Gauzin, Camille Lejards, collaboration with Cécile Malnou – Infinity Toulouse)
– The neural substrates of cognitive reserve (Laure Verret, Fanny Tixier)
– The involvement of mitochondrial dysfunction in adult born-neurons in cognitive impairment in Alzheimer’s disease. (Claire Rampon, Zahra Ghasemi-Abyazani, Sébastien Gauzin, Camille Lejards collaboration avec Pascale Belenguer et Laetitia Arnauné-Pelloquin, Minding Team CRCA).
– The mechanisms of recognition and social memory deficits in Alzheimer’s disease (Laure Verret, Claire Rampon, Lola Fauré, Sébastien Gauzin, Camille Lejards)
– Network dysfunctions in mouse models of Alzheimer’s disease (Laure Verret)
– Epilepsy and associated memory deficits in Alzheimer’s disease (Lionel Dahan, Cécile Merveillie, collaboration with Emmanuel Barbeau and Lionel Nowak – CerCo, Toulouse and Jonathan Curot and Luc Valton – CHU, Toulouse).
Project 2
Current theories of learning and memory suggest that they rely on Long-Term Potentiation (LTP), a mechanism that strengthens synaptic connections based on experience, occurring in the hippocampus. However, these theories do not explain why only certain events are remembered. Our recent work shows that dopamine neurons in the ventral tegmental area (VTA) trigger LTP in the hippocampus and enhance contextual learning. This supports the idea that dopamine acts as a “learning signal,” informing the hippocampus of which experiences should be remembered. We combine optogenetic, in vivo electrophysiology, dopaminergic transmission imaging, and behavioral approaches to address 3 questions:
1. What cellular and molecular mechanisms underlie dopamine-induced LTP? (Lionel Dahan, collaboration with Paula Pousinha, IPMC-Nice and Peter Vanhoutte, IBPS-Paris)
2. What types of events trigger dopamine release in the hippocampus and learning? (Lionel Dahan, collaboration with Yaroslav Sych INCI, Strasbourg)
3. Does dopamine contribute to learning-induced LTP? (Lionel Dahan)
Project 3
Long-term synaptic plasticity and memory formation depend on de novo gene transcription. Epigenetic modifications (via HDAC activity) and chromatin remodeling are key molecular mechanisms that regulate gene expression and memory consolidation in the hippocampus. Furthermore, our recent findings have shown that SIN3A, a scaffolding protein that can recruit different transcription factors, acts as an enhancer of long-term memory. In this project, we propose to understand how regulators of gene expression such as REST, SIN3A or HDAC, act during memory consolidation and age-related memory disorders. Our aim is to provide new insights into the role of epigenetic mechanisms in memory storage and to propose potential new targets for treating memory deficits. (Cédrick Florian, Camille Lejards, Sébastien Gauzin)
Project 4
Many neuropeptides coexist with classical fast-acting neurotransmitters in neurons of the central nervous system and play a modulatory role in brain function. They are particularly important for the modulations of learning and memory associated with the individual’s internal state (arousal, stress, inflammation, reward, etc.). In this context, our work aims to understand the influence of opioid neuropeptidergic systems on memory acquisition and consolidation, with a specific focus on the nociceptin/orphanin FQ (N/OFQ) system and its regulation by stress. Our goal is to identify new therapeutic avenues for treating conditions such as anxiety disorders and depression. Our current projects focus on:
– The modulation of adult neurogenesis in the hippocampus by opioid neuropeptides. (Lionel Moulédous, Claire Rampon, Cathaline Robert, collaboration with Chiara Ruzza, University of Ferrara)
– The involvement of the N/OFQ system in traumatic memory and post-traumatic stress disorder (PTSD) symptoms. (Lionel Moulédous, Cathaline Robert, Bruno Guiard, Sébastien Gauzin)
– The role of the N/OFQ system in hippocampal alterations and cognitive deficits associated with chronic stress. (Lionel Moulédous, Cathaline Robert, collaboration with Dominique Massotte, INCI-Strasbourg)
Project 5
Serotonergic (DOI, LSD, DMT, psilocin, MDMA) and non-serotonergic (ketamine) psychedelics have shown promise as therapies for treatment-resistant depression and post-traumatic stress disorder. They appear to work by stimulating the renewal and the growth of synaptic connections in the brain. How these drugs exactly promote plasticity remains unclear and a number of questions regarding their use in clinical practice such as the dose, frequency and duration of treatment to achieve beneficial effects have yet to be solved. The role of the serotonergic system and the respective contribution of the 5-HT1A and 5-HT2A receptors in their behavioral, cellular and molecular responses represents another gap that we explore. Studies also support that the hallucinogenic effects of psychedelics are required for their therapeutic effects but this notion has been recently challenged prompting us to address this issue. A remaining question is the influence of the extra-pharmacological factors such as the supervised administration (set) in a dedicated environment (setting) on the trajectory of their behavioral effects. We will evaluate the efficacy of psychedelics according to the context of administration. We thus hope to provide experimental evidence of the efficacy of psychedelics and optimize their use with a view to set up clinical trials. (Bruno Guiard, Romain Hacquet)
Team members
– Sayegh, F, Mouledous L, Macri C, Pi Macedo J, Lejards C, Rampon C, Verret L & Dahan L. Ventral tegmental area dopamine projections to the hippocampus trigger long-term potentiation and contextual learning. Nature Com, May 21;15(1):4100. doi: 10.1038/s41467-024-47481-4.
– Viguier C, Bullich S, Botella M, Fasseu L, Alfonso A, Rekik K, Gauzin S, Guiard BP, Davezac N. Impact of physical activity on brain oxidative metabolism and intrinsic capacities in young swiss mice fed a high fat diet Neuropharmacology. 2023 Dec 15;241:109730. doi: 10.1016/j.neuropharm.2023.109730 2023 Dec
– D’Oliveira da Silva F, Robert C, Lardant E, Pizzano C, Bruchas MR, Guiard BP, Chauveau F, Moulédous L. Targeting Nociceptin/Orphanin FQ receptor to rescue cognitive symptoms in a mouse neuroendocrine model of chronic stress Mol Psychiatry. 2024 Mar;29(3):718-729. doi: 10.1038/s41380-023-02363-x
– Andraini T, Moulédous L, Petsophonsakul P, Florian C, Gauzin S, Botella-Daloyau M, Arrázola M, Nikolla K, Philip A, Leydier A, Marque M, Arnauné-Pelloquin L, Belenguer P, Rampon C, Miquel MC. Mitochondrial OPA1 Deficiency Is Associated to Reversible Defects in Spatial Memory Related to Adult Neurogenesis in Mice eNeuro. 2023 Nov 20;10(11):ENEURO.0073-23.2023 2023 Nov
– D’Oliveira da Silva F, Zaveri NT, Moulédous L. Acute single non-sedative doses of NOP receptor agonists affect acquisition of object location memory but repeated high doses do not induce long-lasting deficits Neurobiol Learn Mem. 2023 Nov;205:107841. doi: 10.1016/j.nlm.2023.107841 2023 Nov
– Coutens B, Lejards C, Bouisset G, Verret L, Rampon C, Guiard BP. Enriched environmental exposure reduces the onset of action of the serotonin norepinephrin reuptake inhibitor venlafaxine through its effect on parvalbumin interneurons plasticity in mice Transl Psychiatry. 2023 Jun 26;13(1):227. doi: 10.1038/s41398-023-02519-x 2023 Jun
– B Szabo A, Cattaud V, Bezzina C, Dard RF, Sayegh F, Gauzin S, Lejards C, Valton L, Rampon C, Verret L, Dahan L. Neuronal hyperexcitability in the Tg2576 mouse model of Alzheimer’s disease – the influence of sleep and noradrenergic transmission Neurobiol Aging. 2023 Mar;123:35-48. doi: 10.1016/j.neurobiolaging.2022.11.017 2023 Mar
– Rey CC, Robert V, Bouisset G, Loisy M, Lopez S, Cattaud V, Lejards C, Piskorowski RA, Rampon C, Chevaleyre V, Verret L. iScience. 2022 Feb Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer’s mouse model. 9;25(3):103895. doi: 10.1016/j.isci.2022.103895.
Affiliation
