Isabel Fernaud - Profile on Academia.edu (original) (raw)
Papers by Isabel Fernaud
Applied Sciences
The complexity of the human brain makes its understanding one of the biggest challenges that scie... more The complexity of the human brain makes its understanding one of the biggest challenges that science is currently confronting. Due to its complexity, the brain has been studied at many different levels and from many disciplines and points of view, using a diversity of techniques for getting meaningful data at each specific level and perspective, producing sometimes data that are difficult to integrate. In order to advance understanding of the brain, scientists need new tools that can speed up this analysis process and that can facilitate integrating research results from different disciplines and techniques. Visualization has proved to be useful in the analysis of complex data, and this paper focuses on the design of visualization solutions adapted to the specific problems posed by brain research. In this paper, we propose a unified framework that allows the integration of specific tools to work together in a coordinated manner in a multiview environment, displaying information at d...
PLOS Computational Biology, 2018
The dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cere... more The dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cerebral cortex. They have a wide variety of morphologies, and their morphology appears to be critical from the functional point of view. To further characterize dendritic spine geometry, we used in this paper over 7,000 individually 3D reconstructed dendritic spines from human cortical pyramidal neurons to group dendritic spines using model-based clustering. This approach uncovered six separate groups of human dendritic spines. To better understand the differences between these groups, the discriminative characteristics of each group were identified as a set of rules. Model-based clustering was also useful for simulating accurate 3D virtual representations of spines that matched the morphological definitions of each cluster. This mathematical approach could provide a useful tool for theoretical predictions on the functional features of human pyramidal neurons based on the morphology of dendritic spines.
Cerebral cortex (New York, N.Y. : 1991), Oct 13, 2016
The Reelin pathway is essential for both neural migration and for the development and maturation ... more The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons. In contrast, 3D-electron microscopy (focused ion beam milling/scanning electron microscope) revealed that dysregulation of the Reelin/Dab1 pathway leads to both transient and permanent changes in the types and morphology of dendritic spines, mainly altering mushroom, filopodial, and branched GC spines. We also found that the Reelin/Dab1 pathway controls synaptic configuration of presynaptic boutons in the dentate gyrus, with its dysregulation leading to a substantial...
FIB/SEM reconstruction of identified neurons - Supplementary Movies
Supplementary Movie 5 - 3D reconstruction of the branched spine shown in Supplementary Movie 4
Supplementary Movie 2 - Complete 3D image stack of a labeled 8-week-old GC dendrite
Supplementary Movie 6 - 3D image stack of an 8-week-old GC dendrite illustrating a presynaptic MSB forming up to eight synaptic contacts
Supplementary Movie 3 - 3D reconstruction of the dendritic segment displayed in Movie 1
Supplementary Movie 7 - 3D reconstruction of the MSB and the DAB-stained new-born GC shown in Supplementary Movie 6
Supplementary Movie 1 - Complete 3D image stack of a labeled 8-week-old GC dendrite
Frontiers in Neuroanatomy, 2015
Pérez A and Soriano E (2015) FIB/SEM technology and high-throughput 3D reconstruction of dendriti... more Pérez A and Soriano E (2015) FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons.
Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus
Brain Structure and Function, 2014
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2014
Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell... more Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although…
Hippocampus, 2010
Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) ha... more Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) has long been a fundamental question when considering the mechanisms underlying this disease. It has been established from numerous biochemical and morphological studies that AD is, at least initially, a consequence of synaptic malfunction provoked by Amyloid β (Aβ) peptide. APP/PS1 transgenic mice accumulate Aβ throughout the brain, and they have therefore been employed to investigate the effects of Aβ overproduction on brain circuitry and cognition. Previous studies show that Aβ overproduction affects spine morphology in the hippocampus and amygdala, both within and outside plaques (Knafo et al., (2009) Cereb Cortex 19:586‐592; Knafo et al., (in press) J Pathol). Hence, we conducted a detailed analysis of dendritic spines located in the stratum oriens and stratum radiatum of the CA1 hippocampal subfield of APP/PS1 mice. Three‐dimensional analysis of 18,313 individual dendritic spines rev...
Progress in Neurobiology, 2000
The proteoglycans are multifunctional macromolecules composed of a core polypeptide and a variabl... more The proteoglycans are multifunctional macromolecules composed of a core polypeptide and a variable number of glycosaminoglycan chains. The structural diversity and complexities of proteoglycan expression in the developing and adult Nervous System underlies the variety of biological functions that these molecules ful®ll. Thus, in the Nervous System, proteoglycans regulate the structural organisation of the extracellular matrix, modulate growth factor activities and cellular adhesive and motility events, such as cell migration and axon outgrowth. This review summarises the evidences indicating that proteoglycans have an important role as modulators of neurite outgrowth and neuronal polarity. Special emphasis will be placed on those studies that have shown that proteoglycans of certain subtypes inhibit neurite extension either during the development and/or the regeneration of the vertebrate Central Nervous System.
Musical Representation of Dendritic Spine Distribution: A New Exploratory Tool
Neuroinformatics, 2014
Molecular Immunology, 1998
Neurite Outgrowth Inhibitor of Gliotic Brain Tissue. Mode of Action and Cellular Localization, Studied with Specific Monoclonal Antibodies
European Journal of Neuroscience, 1997
Membranes from injured adult rat brain express a heparan/chondroitin sulphate proteoglycan that i... more Membranes from injured adult rat brain express a heparan/chondroitin sulphate proteoglycan that inhibits neurite outgrowth in vitro. We have developed monoclonal antibodies (Mabs) against this proteoglycan, two of which were characterized and used for the study of the inhibitor mode of action and localization in normal and injured adult brain. The antibodies recognized a molecule of apparent molecular weight 200 kDa in Western blots of injured brain membranes. One of the Mabs blocked both the inhibition of neurite outgrowth and the growth cone collapse activity, associated with the proteoglycan. In adult brain, inhibitor immunoreactivity was found predominantly in neurons but, after a lesion, it was associated mainly with reactive glial cells. The localization of neurite outgrowth inhibitors in reactive glia supports the idea that gliotic tissue is largely responsible for the failure of axonal regeneration in mammalian CNS
Applied Sciences
The complexity of the human brain makes its understanding one of the biggest challenges that scie... more The complexity of the human brain makes its understanding one of the biggest challenges that science is currently confronting. Due to its complexity, the brain has been studied at many different levels and from many disciplines and points of view, using a diversity of techniques for getting meaningful data at each specific level and perspective, producing sometimes data that are difficult to integrate. In order to advance understanding of the brain, scientists need new tools that can speed up this analysis process and that can facilitate integrating research results from different disciplines and techniques. Visualization has proved to be useful in the analysis of complex data, and this paper focuses on the design of visualization solutions adapted to the specific problems posed by brain research. In this paper, we propose a unified framework that allows the integration of specific tools to work together in a coordinated manner in a multiview environment, displaying information at d...
PLOS Computational Biology, 2018
The dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cere... more The dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cerebral cortex. They have a wide variety of morphologies, and their morphology appears to be critical from the functional point of view. To further characterize dendritic spine geometry, we used in this paper over 7,000 individually 3D reconstructed dendritic spines from human cortical pyramidal neurons to group dendritic spines using model-based clustering. This approach uncovered six separate groups of human dendritic spines. To better understand the differences between these groups, the discriminative characteristics of each group were identified as a set of rules. Model-based clustering was also useful for simulating accurate 3D virtual representations of spines that matched the morphological definitions of each cluster. This mathematical approach could provide a useful tool for theoretical predictions on the functional features of human pyramidal neurons based on the morphology of dendritic spines.
Cerebral cortex (New York, N.Y. : 1991), Oct 13, 2016
The Reelin pathway is essential for both neural migration and for the development and maturation ... more The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons. In contrast, 3D-electron microscopy (focused ion beam milling/scanning electron microscope) revealed that dysregulation of the Reelin/Dab1 pathway leads to both transient and permanent changes in the types and morphology of dendritic spines, mainly altering mushroom, filopodial, and branched GC spines. We also found that the Reelin/Dab1 pathway controls synaptic configuration of presynaptic boutons in the dentate gyrus, with its dysregulation leading to a substantial...
FIB/SEM reconstruction of identified neurons - Supplementary Movies
Supplementary Movie 5 - 3D reconstruction of the branched spine shown in Supplementary Movie 4
Supplementary Movie 2 - Complete 3D image stack of a labeled 8-week-old GC dendrite
Supplementary Movie 6 - 3D image stack of an 8-week-old GC dendrite illustrating a presynaptic MSB forming up to eight synaptic contacts
Supplementary Movie 3 - 3D reconstruction of the dendritic segment displayed in Movie 1
Supplementary Movie 7 - 3D reconstruction of the MSB and the DAB-stained new-born GC shown in Supplementary Movie 6
Supplementary Movie 1 - Complete 3D image stack of a labeled 8-week-old GC dendrite
Frontiers in Neuroanatomy, 2015
Pérez A and Soriano E (2015) FIB/SEM technology and high-throughput 3D reconstruction of dendriti... more Pérez A and Soriano E (2015) FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons.
Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus
Brain Structure and Function, 2014
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2014
Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell... more Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although…
Hippocampus, 2010
Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) ha... more Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) has long been a fundamental question when considering the mechanisms underlying this disease. It has been established from numerous biochemical and morphological studies that AD is, at least initially, a consequence of synaptic malfunction provoked by Amyloid β (Aβ) peptide. APP/PS1 transgenic mice accumulate Aβ throughout the brain, and they have therefore been employed to investigate the effects of Aβ overproduction on brain circuitry and cognition. Previous studies show that Aβ overproduction affects spine morphology in the hippocampus and amygdala, both within and outside plaques (Knafo et al., (2009) Cereb Cortex 19:586‐592; Knafo et al., (in press) J Pathol). Hence, we conducted a detailed analysis of dendritic spines located in the stratum oriens and stratum radiatum of the CA1 hippocampal subfield of APP/PS1 mice. Three‐dimensional analysis of 18,313 individual dendritic spines rev...
Progress in Neurobiology, 2000
The proteoglycans are multifunctional macromolecules composed of a core polypeptide and a variabl... more The proteoglycans are multifunctional macromolecules composed of a core polypeptide and a variable number of glycosaminoglycan chains. The structural diversity and complexities of proteoglycan expression in the developing and adult Nervous System underlies the variety of biological functions that these molecules ful®ll. Thus, in the Nervous System, proteoglycans regulate the structural organisation of the extracellular matrix, modulate growth factor activities and cellular adhesive and motility events, such as cell migration and axon outgrowth. This review summarises the evidences indicating that proteoglycans have an important role as modulators of neurite outgrowth and neuronal polarity. Special emphasis will be placed on those studies that have shown that proteoglycans of certain subtypes inhibit neurite extension either during the development and/or the regeneration of the vertebrate Central Nervous System.
Musical Representation of Dendritic Spine Distribution: A New Exploratory Tool
Neuroinformatics, 2014
Molecular Immunology, 1998
Neurite Outgrowth Inhibitor of Gliotic Brain Tissue. Mode of Action and Cellular Localization, Studied with Specific Monoclonal Antibodies
European Journal of Neuroscience, 1997
Membranes from injured adult rat brain express a heparan/chondroitin sulphate proteoglycan that i... more Membranes from injured adult rat brain express a heparan/chondroitin sulphate proteoglycan that inhibits neurite outgrowth in vitro. We have developed monoclonal antibodies (Mabs) against this proteoglycan, two of which were characterized and used for the study of the inhibitor mode of action and localization in normal and injured adult brain. The antibodies recognized a molecule of apparent molecular weight 200 kDa in Western blots of injured brain membranes. One of the Mabs blocked both the inhibition of neurite outgrowth and the growth cone collapse activity, associated with the proteoglycan. In adult brain, inhibitor immunoreactivity was found predominantly in neurons but, after a lesion, it was associated mainly with reactive glial cells. The localization of neurite outgrowth inhibitors in reactive glia supports the idea that gliotic tissue is largely responsible for the failure of axonal regeneration in mammalian CNS