Neurocentre Magendie

Sophie TRONEL




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Expertise: memory, consolidation, reconsolidation, neurogenesis, hippocampus, amygdala



I am working in the field of Learning and Memory since my PhD that I obtained in 2003 under the supervision of Susan SARA at University Paris VI. I then moved to New York (NY, USA) where I did a postdoctoral fellowship in the lab of Cristina Alberini at Mount Sinai School of Medicine. There I worked on the molecular basis of memory reconsolidation.

 In 2007, I came back to France to join the team of Nora Abrous in Bordeaux. I switched to the field of adult neurogenesis. I got my tenure position at the CNRS in 2011. Since then, My research is focused on the role of adult hippocampal neurons in the stabilisation of memory, in particular in the process of reconsolidation.



15 publication(s) depuis Mai 2002:


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25/04/2015 | Hippocampus   IF 4.1
Adult-born dentate neurons are recruited in both spatial memory encoding and retrieval.
Tronel S, Charrier V, Sage C, Maitre M, Leste-Lasserre T, Abrous DN

Abstract:
Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key structure in learning and memory. Adult-generated granule cells have been shown to play a role in spatial memory processes such as acquisition or retrieval, in particular during an immature stage when they exhibit a period of increased plasticity. Here, we demonstrate that immature and mature neurons born in the dentate gyrus of adult rats are similarly activated in spatial memory processes. By imaging the activation of these two different neuron generations in the same rat and by using the immediate early gene Zif268, we show that these neurons are involved in both spatial memory acquisition and retrieval. These results demonstrate that adult-generated granule cells are involved in memory beyond their immaturity stage. This article is protected by copyright. All rights reserved.




09/02/2014 | Brain Struct Funct   IF 5.8
Influence of ontogenetic age on the role of dentate granule neurons.
Tronel S, Lemaire V, Charrier V, Montaron MF, Abrous DN

Abstract:
New neurons are continuously produced in the adult dentate gyrus of the hippocampus, a key structure in learning and memory. It has been shown that adult neurogenesis is crucial for normal memory processing. However, it is not known whether neurons born during the developmental period and during adulthood support the same functions. Here, we demonstrate that neurons born in neonates (first postnatal week) are activated in different memory processes when they are mature compared to neurons born in adults. By imaging the activation of these two different neuron generations in the same rat and using the IEG Zif268 and Fos, we show that these neurons are involved in discriminating dissimilar contexts and spatial problem solving, respectively. These findings demonstrate that the ontogenetic stage during which neurons are generated is crucial for their function within the memory network.




20/02/2013 | J Neurosci   IF 5.9
CCAAT Enhancer Binding Protein delta Plays an Essential Role in Memory Consolidation and Reconsolidation.
Arguello AA, Ye X, Bozdagi O, Pollonini G, Tronel S, Bambah-Mukku D, Huntley GW, Platano D, Alberini CM

Abstract:
A newly formed memory is temporarily fragile and becomes stable through a process known as consolidation. Stable memories may again become fragile if retrieved or reactivated, and undergo a process of reconsolidation to persist and strengthen. Both consolidation and reconsolidation require an initial phase of transcription and translation that lasts for several hours. The identification of the critical players of this gene expression is key for understanding long-term memory formation and persistence. In rats, the consolidation of inhibitory avoidance (IA) memory requires gene expression in both the hippocampus and amygdala, two brain regions that process contextual/spatial and emotional information, respectively; IA reconsolidation requires de novo gene expression in the amygdala. Here we report that, after IA learning, the levels of the transcription factor CCAAT enhancer binding protein delta (C/EBPdelta) are significantly increased in both the hippocampus and amygdala. These increases are essential for long-term memory consolidation, as their blockade via antisense oligodeoxynucleotide-mediated knockdown leads to memory impairment. Furthermore, C/EBPdelta is upregulated and required in the amygdala for IA memory reconsolidation. C/EBPdelta is found in nuclear, somatic, and dendritic compartments, and a dendritic localization of C/EBPdelta mRNA in hippocampal neuronal cultures suggests that this transcription factor may be translated at synapses. Finally, the induction of long-term potentiation at CA3-CA1 synapses by tetanic stimuli in acute slices, a cellular model of long-term memory, leads to an accumulation of C/EBPdelta in the nucleus. We conclude that the transcription factor C/EBPdelta plays a critical role in memory consolidation and reconsolidation.




17/05/2012 | Hippocampus   IF 4.1
Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice.
Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Laye S, Ferreira G

Abstract:
Increased consumption of high-fat diet (HFD) leads to obesity and adverse neurocognitive outcomes. Childhood and adolescence are important periods of brain maturation shaping cognitive function. These periods could consequently be particularly sensitive to the detrimental effects of HFD intake. In mice, juvenile and adulthood consumption of HFD induce similar morphometric and metabolic changes. However, only juvenile exposure to HFD abolishes relational memory flexibility, assessed after initial radial-maze concurrent spatial discrimination learning, and decreases neurogenesis. Our results identify a critical period of development covering adolescence with higher sensitivity to HFD-induced hippocampal dysfunction at both behavioral and cellular levels. (c) 2012 Wiley Periodicals, Inc.




29/02/2012 | J Neurosci   IF 5.9
Long-lasting plasticity of hippocampal adult-born neurons.
Lemaire V, Tronel S, Montaron MF, Fabre A, Dugast E, Abrous DN

Abstract:
Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key structure in learning and memory. It is believed that adult-born neurons exert their unique role in information processing due to their high plasticity during immature stage that renders them malleable in response to environmental demands. Here, we demonstrate that, in rats, there is no critical time window for experience-induced dendritic plasticity of adult-born neurons as spatial learning in the water maze sculpts the dendritic arbor of adult-born neurons even when they are several months of age. By ablating neurogenesis within a specific period of time, we found that learning was disrupted when the delay between ablation and learning was extended to several months. Together, these results show that mature adult-born neurons are still plastic when they are functionally integrated into dentate network. Our results suggest a new perspective with regard to the role of neo-neurons by highlighting that even mature ones can provide an additional source of plasticity to the brain to process memory information.




02/2012 | Hippocampus   IF 4.1
Adult-born neurons are necessary for extended contextual discrimination.
Tronel S, Belnoue L, Grosjean N, Revest JM, Piazza PV, Koehl M, Abrous DN

Abstract:
New neurons are continuously produced in the adult dentate gyrus of the hippocampus. It has been shown that one of the functions of adult neurogenesis is to support spatial pattern separation, a process that transforms similar memories into nonoverlapping representations. This prompted us to investigate whether adult-born neurons are required for discriminating two contexts, i.e., for identifying a familiar environment and detect any changes introduced in it. We show that depleting adult-born neurons impairs the animal's ability to disambiguate two contexts after extensive training. These data suggest that the continuous production of new dentate neurons plays a crucial role in extracting and separating efficiently contextual representation in order to discriminate features within events.




27/04/2010 | Proc Natl Acad Sci U S A   IF 9.6
Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons.
Tronel S, Fabre A, Charrier V, Oliet SH, Gage FH, Abrous DN

Abstract:
Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviving neurons (a key parameter for synaptic integration and signal processing) is unknown. Here we show that learning accelerates the maturation of their dendritic trees and their integration into the hippocampal network. We demonstrate that these learning effects on dendritic arbors are homeostatically regulated, persist for several months, and are specific to neurons born during adulthood. Finally, we show that this dendritic shaping depends on the cognitive demand and relies on the activation of NMDA receptors. In the search for the structural changes underlying long-term memory, these findings lead to the conclusion that shaping neo-networks is important in forming spatial memories.




24/09/2008 | J Neurosci   IF 5.9
The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism.
Bozdagi O, Rich E, Tronel S, Sadahiro M, Patterson K, Shapiro ML, Alberini CM, Huntley GW, Salton SR

Abstract:
VGF is a neurotrophin-inducible, activity-regulated gene product that is expressed in CNS and PNS neurons, in which it is processed into peptides and secreted. VGF synthesis is stimulated by BDNF, a critical regulator of hippocampal development and function, and two VGF C-terminal peptides increase synaptic activity in cultured hippocampal neurons. To assess VGF function in the hippocampus, we tested heterozygous and homozygous VGF knock-out mice in two different learning tasks, assessed long-term potentiation (LTP) and depression (LTD) in hippocampal slices from VGF mutant mice, and investigated how VGF C-terminal peptides modulate synaptic plasticity. Treatment of rat hippocampal slices with the VGF-derived peptide TLQP62 resulted in transient potentiation through a mechanism that was selectively blocked by the BDNF scavenger TrkB-Fc, the Trk tyrosine kinase inhibitor K252a (100 nm), and tPA STOP, an inhibitor of tissue plasminogen activator (tPA), an enzyme involved in pro-BDNF cleavage to BDNF, but was not blocked by the NMDA receptor antagonist APV, anti-p75(NTR) function-blocking antiserum, or previous tetanic stimulation. Although LTP was normal in slices from VGF knock-out mice, LTD could not be induced, and VGF mutant mice were impaired in hippocampal-dependent spatial learning and contextual fear conditioning tasks. Our studies indicate that the VGF C-terminal peptide TLQP62 modulates hippocampal synaptic transmission through a BDNF-dependent mechanism and that VGF deficiency in mice impacts synaptic plasticity and memory in addition to depressive behavior.




Abstract:
BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, which include alterations in glucocorticoid secretion and critically involve the limbic system, in particular the amygdala. Important symptoms of PTSD manifest as a classical conditioning to fear, which recurs each time trauma-related cues remind the subject of the original insult. Traumatic memories based on fear conditioning can be disrupted if interfering events or pharmacological interventions are applied following their retrieval. METHODS AND RESULTS: Using an animal model, here we show that a traumatic memory is persistently disrupted if immediately after its retrieval glucocorticoid receptors are inactivated in the amygdala. The disruption of the memory is long lasting and memory retention does not re-emerge following strong reminders of the conditioned fear. CONCLUSIONS: We propose that a combinatorial approach of psychological and pharmacological intervention targeting the glucocorticoid system following memory retrieval may represent a novel direction for the treatment of PTSD.




05/2006 | Cell Mol Life Sci   IF 5.7
Mechanisms of memory stabilization and de-stabilization.
Alberini CM , Milekic MH , Tronel S

Abstract:
Memories become stabilized through a time-dependent process that requires gene