Search

Your search keyword '"Simona Gribaudo"' showing total 15 results
Start Over Author "Simona Gribaudo"
15 results on '"Simona Gribaudo"'

1. Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network

Author

Simona Gribaudo, Philippe Tixador, Luc Bousset, Alexis Fenyi, Patricia Lino, Ronald Melki, Jean-Michel Peyrin, and Anselme L. Perrier

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Summary: Reappraisal of neuropathological studies suggests that pathological hallmarks of Alzheimer’s disease and Parkinson’s disease (PD) spread progressively along predictable neuronal pathways in the human brain through unknown mechanisms. Although there is much evidence supporting the prion-like propagation and amplification of α-synuclein (α-Syn) in vitro and in rodent models, whether this scenario occurs in the human brain remains to be substantiated. Here we reconstructed in microfluidic devices corticocortical neuronal networks using human induced pluripotent stem cells derived from a healthy donor. We provide unique experimental evidence that different strains of human α-Syn disseminate in “wild-type” human neuronal networks in a prion-like manner. We show that two distinct α-Syn strains we named fibrils and ribbons are transported, traffic between neurons, and trigger to different extents, in a dose- and structure-dependent manner, the progressive accumulation of PD-like pathological hallmarks. We further demonstrate that seeded aggregation of endogenous soluble α-Syn affects synaptic integrity and mitochondria morphology. : In this article, Gribaudo and colleagues report the internalization and trafficking of exogenous α-synuclein fibrils and ribbons through fluidically isolated cortical networks derived from wild-type human iPSCs. These assemblies trigger via seeding mechanisms the accumulation of endogenous phosphorylated α-synuclein, in a structure-, dose-, and time-dependent manner. Phosphorylated α-Syn structures resist degradation and accumulate in the cytoplasm of neurons, affecting Ca2+ homeostasis and mitochondria morphology. Keywords: human pluripotent stem cells, Parkinson's disease, microfluidic, prion-like, nucleation, synuclein, Lewy body, human cortical neuron, neuronal dysfunction

Published
2019
Full Text
View/download PDF

2. A role for dendritic translation of CaMKIIα mRNA in olfactory plasticity.

Author

Marie Néant-Fery, Eléonore Pérès, Carole Nasrallah, Monica Kessner, Simona Gribaudo, Charles Greer, Anne Didier, Alain Trembleau, and Isabelle Caillé

Subjects
Medicine, Science
Abstract

Local protein synthesis in dendrites contributes to the synaptic modifications underlying learning and memory. The mRNA encoding the α subunit of the calcium/calmodulin dependent Kinase II (CaMKIIα) is dendritically localized and locally translated. A role for CaMKIIα local translation in hippocampus-dependent memory has been demonstrated in mice with disrupted CaMKIIα dendritic translation, through deletion of CaMKIIα 3'UTR. We studied the dendritic localization and local translation of CaMKIIα in the mouse olfactory bulb (OB), the first relay of the olfactory pathway, which exhibits a high level of plasticity in response to olfactory experience. CaMKIIα is expressed by granule cells (GCs) of the OB. Through in situ hybridization and synaptosome preparation, we show that CaMKIIα mRNA is transported in GC dendrites, synaptically localized and might be locally translated at GC synapses. Increases in the synaptic localization of CaMKIIα mRNA and protein in response to brief exposure to new odors demonstrate that they are activity-dependent processes. The activity-induced dendritic transport of CaMKIIα mRNA can be inhibited by an NMDA receptor antagonist and mimicked by an NMDA receptor agonist. Finally, in mice devoid of CaMKIIα 3'UTR, the dendritic localization of CaMKIIα mRNA is disrupted in the OB and olfactory associative learning is severely impaired. Our studies thus reveal a new functional modality for CaMKIIα local translation, as an essential determinant of olfactory plasticity.

Published
2012
Full Text
View/download PDF

3. New striatal neurons in a mouse model of progressive striatal degeneration are generated in both the subventricular zone and the striatal parenchyma.

Author

Federico Luzzati, Silvia De Marchis, Rosanna Parlato, Simona Gribaudo, Günther Schütz, Aldo Fasolo, and Paolo Peretto

Subjects
Medicine, Science
Abstract

Acute striatal lesions increase proliferation in the subventricular zone (SVZ) and induce migration of SVZ neuroblasts to the striatum. However, the potential of these cells to replace acutely degenerated neurons is controversial. The possible contribution of parenchymal progenitors to striatal lesion-induced neurogenesis has been poorly explored. Here, we present a detailed investigation of neurogenesis in the striatum of a mouse model showing slow progressive neurodegeneration of striatal neurons, the Creb1(Camkcre4)Crem⁻/⁻ mutant mice (CBCM). By using BrdU time course analyses, intraventricular injections of a cell tracker and 3D reconstructions we showed that neurodegeneration in CBCM mice stimulates the migration of SVZ neuroblasts to the striatum without altering SVZ proliferation. SVZ-neuroblasts migrate as chains through the callosal striatal border and then enter within the striatal parenchyma as individual cells. In addition, a population of clustered neuroblasts showing high turnover rates were observed in the mutant striatum that had not migrated from the SVZ. Clustered neuroblasts might originate within the striatum itself because they are specifically associated with parenchymal proliferating cells showing features of intermediate neuronal progenitors such as clustering, expression of EGF receptor and multiple glial (SOX2, SOX9, BLBP) and neuronal (Dlx, Sp8, and to some extent DCX) markers. Newborn striatal neurons had a short lifespan and did not replace projection neurons nor expressed sets of transcription factors involved in their specification. The differentiation failure of endogenous neuroblasts likely occurred cell autonomously because transplanted wild type embryonic precursors correctly differentiated into striatal projection neurons. Thus, we propose that under progressive degeneration, neither SVZ derived nor intra-striatal generated neurons have the potential to differentiate into striatal projection neurons.

Published
2011
Full Text
View/download PDF

4. Propagation of Distinct α-Synuclein Strains Within Human Reconstructed Neuronal Network and Associated Neuronal Dysfunctions

Author

Simona Gribaudo, Luc Bousset, Josquin Courte, Ronald Melki, Jean-Michel Peyrin, Anselme L. Perrier, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), and Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon

Subjects
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

International audience; Abstract Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients’ glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients’ tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients’ tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients’ tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes.

Published
2022
Full Text
View/download PDF

5. Propagation of Distinct α-Synuclein Strains Within Human Reconstructed Neuronal Network and Associated Neuronal Dysfunctions

Author

Simona, Gribaudo, Luc, Bousset, Josquin, Courte, Ronald, Melki, Jean-Michel, Peyrin, and Anselme L, Perrier

Subjects
Neurons, Synucleinopathies, Prions, alpha-Synuclein, Humans, Parkinson Disease
Abstract

Aggregated alpha-synuclein (α-Syn) in neurons is a hallmark of Parkinson's disease (PD) and other synucleinopathies. Recent advances (1) in the production and purification of synthetic assemblies of α-Syn, (2) in the design and production of microfluidic devices allowing the construction of oriented and compartmentalized neuronal network on a chip, and (3) in the differentiation of human pluripotent stem cells (hPSCs) into specific neuronal subtypes now allow the study of cellular and molecular determinants of the prion-like properties of α-Syn in vitro. Here, we described the methods we used to reconstruct a cortico-cortical human neuronal network in microfluidic devices and how to take advantage of this cellular model to characterize (1) the prion-like properties of different α-Syn strains and (2) the neuronal dysfunctions and the alterations associated with the exposure to α-Syn strains or the nucleation of endogenous α-Syn protein in vitro.

Published
2022

6. Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification

Author

Hynek Wichterle, Virginie Rouiller-Fabre, Nour Nicolas, Gist F. Croft, Vincent Mouilleau, Vanessa Ribes, Léa Lesueur, Célia Vaslin, Mathieu Daynac, Stéphane Nedelec, Angélique Terray, Margot Jarrige, Simona Gribaudo, Mackenzie W. Mathis, Cécile Martinat, Rémi Robert, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stem cells in neurodevelopment (SCN), Institut du Fer à Moulin (UMR-S 1270), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Columbia University [New York], Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This project was supported by grants from AVENIR/ATIP, Association Française contre les Myopathies (AFM) and Laboratoire d’Excellence (Labex) Biopsy and Revive (Investissement d’Avenir (ANR-10-LABX-73 and 11-LABX-0035, respectively). V.M has received fellowships from Domaine d’Investissement Majeur (DIM) 'Biothérapies' of the region Ile-de-France and from the Fondation pour la Recherche Médicale (FRM). C.V. is supported by a PhD fellowship of the French Ministry of Research. V.R. and S.N salaries are funded by the INSERM, ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011), Université Paris Cité, Equipe HAL, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Laboratoire de Psychiatrie Biologique - - BIOPSY2011 - ANR-11-LABX-0035 - LABX - VALID, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
MESH: Signal Transduction, MESH: Mammalian, MESH: Bone Morphogenetic Proteins, [SDV]Life Sciences [q-bio], Fibroblast growth factor, MESH: Spinal Cord, MESH: Benzamides, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, MESH: Embryonic Development, Induced pluripotent stem cell, Hox gene, Motor Neurons, 0303 health sciences, patterning, Gene Expression Regulation, Developmental, Cell Differentiation, axial, HOX genes, ES cells, Chromatin, Growth Differentiation Factors, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Benzamides, Bone Morphogenetic Proteins, embryonic structures, MESH: Pluripotent Stem Cells, Stem cell, pluripotent stem cells, MESH: Fibroblast Growth Factors, MESH: Motor Neurons, Signal Transduction, MESH: Cell Differentiation, animal structures, MESH: Circadian Clocks, Human Development, Embryonic Development, Biology, 03 medical and health sciences, Circadian Clocks, MESH: Homeodomain Proteins, medicine, Humans, human, Progenitor cell, motor neuron, Molecular Biology, 030304 developmental biology, Homeodomain Proteins, MESH: Humans, MESH: Embryo, Diphenylamine, spinal cord, Motor neuron, Embryo, Mammalian, NMP, MESH: Growth Differentiation Factors, MESH: Diphenylamine, Fibroblast Growth Factors, Pyrimidines, MESH: Pyrimidines, GDF11, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Rostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX genes within axial stem cells that fuel axial embryo elongation. Whether the pace of sequential activation of HOX genes, the 'HOX clock', is controlled by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in human pluripotent stem cell-derived axial progenitors differentiating into diverse spinal cord motor neuron subtypes. We show that the progressive activation of caudal HOX genes is controlled by a dynamic increase in FGF signaling. Blocking the FGF pathway stalled induction of HOX genes, while a precocious increase of FGF, alone or with GDF11 ligand, accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The pacing of the HOX clock is thus dynamically regulated by exposure to secreted cues. Its manipulation by extrinsic factors provides synchronized access to multiple human neuronal subtypes of distinct rostro-caudal identities for basic and translational applications. This article has an associated ‘The people behind the papers’ interview.

Published
2021
Full Text
View/download PDF

7. Dynamic extrinsic pacing of theHOXclock in human axial progenitors controls motor neuron subtype specification

Author

Hynek Wichterle, Mackenzie W. Mathis, Vincent Mouilleau, Gist F. Croft, Vanessa Ribes, Stéphane Nedelec, Simona Gribaudo, Nour Nicolas, Virginie Rouiller-Fabre, Mathieu Daynac, Angélique Terray, Margot Jarrige, Célia Vaslin, Léa Lesueur, Rémi Robert, and Cécile Martinat

Subjects
medicine.anatomical_structure, GDF11, medicine, Stem cell, Biology, Progenitor cell, Motor neuron, Induced pluripotent stem cell, Fibroblast growth factor, Hox gene, Chromatin, Cell biology
Abstract

SUMMARYRostro-caudal patterning of vertebrates depends on the temporally progressive activation ofHOXgenes within axial stem cells that fuel axial embryo elongation. WhetherHOXgenes sequential activation, the “HOXclock”, is paced by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studiedHOXclock pacing in human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are progenies of axial progenitors. We show that the progressive activation of caudalHOXgenes in axial progenitors is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway stalled induction ofHOXgenes, while precocious increase in FGF alone, or with GDF11 ligand, accelerated theHOXclock. Cells differentiated under acceleratedHOXinduction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. TheHOXclock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized access to human cells of multiple, defined, rostro-caudal identities for basic and translational applications.

Published
2020
Full Text
View/download PDF

8. CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior

Author

Delphine Hardy, Isabelle Caillé, Laura Daroles, Paul De Koninck, Sarah Malvaut, Martin Holzenberger, Daniel Côté, Simona Gribaudo, Marie-Anne Lebel-Cormier, Linda Suzanne David, Zayna Chaker, Armen Saghatelyan, Alain Trembleau, Simon Labrecque, CERVO Brain Research Center, Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Développement et plasticité des réseaux neuronaux = Development and Plasticity of Neural Networks (NPS-14), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Laval, Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Laval [Québec] (ULaval), Faculté de médecine de l'Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and HAL-UPMC, Gestionnaire

Subjects
Male, 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Olfaction, Biology, Inhibitory postsynaptic potential, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Neurochemical, Perceptual learning, Animals, Habituation, Neurons, Behavior, Animal, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Olfactory Perception, Olfactory Bulb, Olfactory bulb, Mice, Inbred C57BL, 030104 developmental biology, Odor, Odorants, Calcium-Calmodulin-Dependent Protein Kinase Type 2, General Agricultural and Biological Sciences, Immediate early gene, Neuroscience, 030217 neurology & neurosurgery
Abstract

Granule cells (GCs) in the olfactory bulb (OB) play an important role in odor information processing. Although they have been classified into various neurochemical subtypes, the functional roles of these subtypes remain unknown. We used in vivo two-photon Ca2+ imaging combined with cell-type-specific identification of GCs in the mouse OB to examine whether functionally distinct GC subtypes exist in the bulbar network. We showed that half of GCs express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα+) and that these neurons are preferentially activated by olfactory stimulation. The higher activity of CaMKIIα+ neurons is due to the weaker inhibitory input that they receive compared to their CaMKIIα-immunonegative (CaMKIIα-) counterparts. In line with these functional data, immunohistochemical analyses showed that 75%-90% of GCs expressing the immediate early gene cFos are CaMKIIα+ in naive animals and in mice that have been exposed to a novel odor and go/no-go operant conditioning, or that have been subjected to long-term associative memory and spontaneous habituation/dishabituation odor discrimination tasks. On the other hand, a perceptual learning task resulted in increased activation of CaMKIIα- cells. Pharmacogenetic inhibition of CaMKIIα+ GCs revealed that this subtype is involved in habituation/dishabituation and go/no-go odor discrimination, but not in perceptual learning. In contrast, pharmacogenetic inhibition of GCs in a subtype-independent manner affected perceptual learning. Our results indicate that functionally distinct populations of GCs exist in the OB and that they play distinct roles during different odor tasks.

Published
2017
Full Text
View/download PDF

9. Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning

Author

Nathalie Mandairon, Caroline Dubacq, Alain Trembleau, Charles A. Greer, Anne Didier, Laura Daroles, Mohamed Doulazmi, Sophie Scotto-Lomassese, Isabelle Caillé, Simona Gribaudo, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des processus adaptatifs (NPA), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Research Council of Canada (NRC), Institut Technique de la Betterave (ITB), Confédération Générale des Planteurs de Betteraves, Université Paris Diderot - Paris 7 (UPD7), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Autism Spectrum Disorder, Dendritic Spines, Neurogenesis, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biology, Adult neurogenesis, Fragile X mental retardation protein, Mice, 03 medical and health sciences, 0302 clinical medicine, Olfactory bulb, medicine, Animals, Learning, RNA, Messenger, Biological Psychiatry, G alpha subunit, Mice, Knockout, Structural plasticity, Messenger RNA, Neuronal Plasticity, Metabotropic glutamate receptor 5, Translation (biology), Dendrites, Olfactory Perception, medicine.disease, Mice, Inbred C57BL, Fragile X syndrome, Disease Models, Animal, 030104 developmental biology, Fragile X Syndrome, Local translation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Olfactory Learning, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. METHODS: Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. RESULTS: Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. CONCLUSIONS: Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause.

Published
2015
Full Text
View/download PDF

10. Fabrication of precisely aligned microwire and microchannel structures: Toward heat stimulation of guided neurites in neuronal cultures

Author

Ka My Dang, Bastian Haberkorn, Simona Gribaudo, Jan Schnitker, Philipp Rinklin, Stefan Weigel, Michael Daenen, Bernhard Wolfrum, Jorne Carolus, Anselme L. Perrier, K. Zobel, Andreas Offenhäusser, and Harald Luksch

Subjects
Microchannel, Fabrication, Materials science, Neurite, 010401 analytical chemistry, Nanotechnology, 02 engineering and technology, Surfaces and Interfaces, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Thermal stimulation, Etching (microfabrication), Materials Chemistry, Electrical and Electronic Engineering, 0210 nano-technology, Layer (electronics)
Abstract

Microwire arrays are a powerful tool for the exertion of localized thermal stress on cellular networks. Combining microwire arrays with a set of orthogonal axon-guiding microchannels on-chip allows for the positioning of neurites, as well as control over their polarity. In this paper, we present a new fabrication approach, based on standard clean room fabrication and sacrificial layer etching, for the integration of microwire arrays into neurite guiding structures. The system permits the application of strong temperature gradients, enabling localized thermal stimulation inside microchannels.

Published
2017
Full Text
View/download PDF

11. From progenitors to integrated neurons: role of neurotransmitters in adult olfactory neurogenesis

Author

Aldo Fasolo, Simona Gribaudo, Adam C. Puche, Silvia De Marchis, and Serena Bovetti

Subjects
Adult, Neurons, Neurotransmitter Agents, Interneuron, Dentate gyrus, Neurogenesis, Stem Cells, Subventricular zone, Cell Differentiation, Biology, Olfactory Bulb, Subgranular zone, Olfactory bulb, Cellular and Molecular Neuroscience, Lateral ventricles, Neuropoiesis, medicine.anatomical_structure, nervous system, medicine, Animals, Humans, Neuroscience, Cellular Senescence
Abstract

Adult neurogenesis is due to the persistence of pools of constitutive stem cells able to give rise to a progeny of proliferating progenitors. In rodents, adult neurogenic niches have been found in the subventricular zone (SVZ) along the lateral ventricles and in the subgranular zone of the dentate gyrus in the hippocampus. SVZ progenitors undergo a unique process of tangential migration from the lateral ventricle to the olfactory bulb (OB) where they differentiate mainly into GABAergic interneurons in the granule and glomerular layers. SVZ progenitor proliferation, migration and differentiation into fully integrated neurons, are strictly related processes regulated by complex interactions between cell intrinsic and extrinsic influences. Numerous observations demonstrate that neurotrasmitters are involved in all steps of the adult neurogenic process, but the understanding of their role is hampered by their intricate mechanism of action and by the highly complex network in which neurotransmitters work. By considering the three main steps of olfactory adult neurogenesis (proliferation, migration and integration), this review will discuss recent advances in the study of neurotransmitters, highlighting the regulatory mechanisms upstream and downstream their action.

Published
2010

12. Extracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identities

Author

Simona Gribaudo, Kazuaki Yoshikawa, Ketty Leto, Silvia De Marchis, Chiara Rolando, and Ferdinando Rossi

Subjects
neural progenitor, Ganglionic eminence, Central nervous system, Green Fluorescent Proteins, Subventricular zone, Biology, Prosencephalon, Interneurons, Cortex (anatomy), Cerebellum, medicine, Animals, Progenitor cell, Rats, Wistar, Stem Cell Niche, Cells, Cultured, Embryonic Stem Cells, differentiation, GABAergic interneuron, heterotopic transplantation, phenotype specification, stem cell, Neurons, General Neuroscience, Stem Cells, Spinal cord, Rats, medicine.anatomical_structure, nervous system, Cytoarchitecture, Animals, Newborn, Cerebellar Nuclei, Stem cell, Rats, Transgenic, Neuroscience, Stem Cell Transplantation
Abstract

Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host-specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region-specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar-specific regulatory genes. In addition, their major structural features, the expression profiles of type-specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear-cut cerebellar identities.

Published
2010

15. Transitory and activity-dependent expression of neurogranin in olfactory bulb tufted cells during mouse postnatal development

Author

Olivier Friard, Livio Oboti, Aldo Fasolo, Serena Bovetti, S. De Marchis, Marion Denorme, and Simona Gribaudo

Subjects
medicine.medical_specialty, Cell Count, Mice, Inbred Strains, Biology, Mice, Postsynaptic potential, Antibody Specificity, Interneurons, Internal medicine, Neuroplasticity, medicine, Animals, Neurogranin, Cell Shape, Neuronal Plasticity, General Neuroscience, Age Factors, Dendrites, Granule cell, Olfactory Bulb, Olfactory bulb, medicine.anatomical_structure, Endocrinology, Tufted cell, Animals, Newborn, Activity-dependent plasticity, GABAergic, Sensory Deprivation
Abstract

Neurogranin (Ng) is a brain-specific postsynaptic calmodulin-binding protein involved in synaptic activity-dependent plasticity. In the adult olfactory bulb (OB), Ng is expressed by a large population of GABAergic interneurons in the granule cell layer. We show here that, during postnatal development, Ng is also expressed by OB neurons in the superficial external plexiform layer (sEPL) and glomerular layer (GL). These Ng-positive neurons display morphological and neurochemical features of superficial and external tufted cells. Ng expression in these cells is transient during OB development: few elements express Ng at postnatal day (P) 5, increasing in number and reaching a peak at P10, then progressively decreasing. At P30, Ng is rarely detectable in these neurons. Ng expression in developing tufted cells is also modulated at the cellular level: at earlier stages, Ng labeling is distributed throughout the cell body and dendritic arborization in the GL, but, at P20, when the glomerular circuits are fully matured, Ng becomes restricted to the soma and proximal portion of tufted cell apical dendrites. We show that olfactory deprivation at early postnatal stages induces a strong increase in Ng-positive tufted cells from P10 to P20, whereas no changes have been observed following olfactory deprivation in adult mice. These findings demonstrate that Ng expression in sEPL-GL is restricted to developmental stages and indicate its activity-dependent regulation in a time window critical for glomerular circuit development, suggesting a role for Ng in maturation and dendritic remodeling of tufted cells.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results