Author
Laura López-Mascaraque
Other affiliations: Salk Institute for Biological Studies, Washington University in St. Louis, Cajal Institute
Bio: Laura López-Mascaraque is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Olfactory bulb & Olfactory system. The author has an hindex of 31, co-authored 77 publications receiving 2990 citations. Previous affiliations of Laura López-Mascaraque include Salk Institute for Biological Studies & Washington University in St. Louis.
Papers published on a yearly basis
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TL;DR: It is concluded that cells of the primary olfactory cortex derive from the lateral ganglionic eminence and that some early generated cells migrating from the longitudinal eminence transgress the cortico-striatal boundary entering the preplate of the neocortical primordium.
Abstract: From previous developmental studies, it has been proposed that the neurons of the ventrolateral cortex, including the primary olfactory cortex, differentiate from progenitor cells in the lateral ganglionic eminence. The objective of the present study was to test this hypothesis. The cells first generated in the forebrain of the rat migrate to the surface of the telencephalic vesicle by embryonic day (E) 12. Using [ 3 H]thymidine, we found that most of these cells contributed to the formation of the deep layer III of the primary olfactory cortex. To study the migratory routes of these cells, we made localized injections of the carbocyanine fluorescent tracers DiI and DiA into various parts of the lateral ganglionic eminence in living embryos at E12–E14 and subsequently maintained the embryos in a culture device for 17–48 hr. After fixation, most migrating cells were located at the surface of the telencephalic vesicle, whereas others were seen coursing tangentially into the preplate. Injections made at E13 and in fixed tissue at E15 showed that migrating cells follow radial glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral surface of the telencephalic vesicle. The spatial distribution of radial glial fibers was studied in Golgi preparations, and these observations provided further evidence of the existence of long glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral cortex. We conclude that cells of the primary olfactory cortex derive from the lateral ganglionic eminence and that some early generated cells migrating from the lateral ganglionic eminence transgress the cortico-striatal boundary entering the preplate of the neocortical primordium.
410 citations
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TL;DR: It is found that removal of NR3A is required to develop strong NMDAR currents, full expression of long-term synaptic plasticity, a mature synaptic organization characterized by more synapses and larger postsynaptic densities, and the ability to form long- term memories.
147 citations
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TL;DR: A novel strategy to analyze cell lineages through the combinatorial expression of fluorescent proteins produces inheritable marks that enable the long-term in vivo tracing of glial progenitor lineages and reinforces the view that lineage origin impinges on cell heterogeneity.
Abstract: Astrocytes are the most numerous cell type in the brain, wherethey are known to play multiple important functions. While there isincreasing evidence of their morphological, molecular, and func-tional heterogeneity, it is not clear whether their positional andmorphological identities are specified during brain development. Weaddress this problem with a novel strategy to analyze cell lineagesthrough the combinatorial expression of fluorescent proteins. Fol-lowing in utero electroporation, stochastic expression of these pro-teins produces inheritable marks that enable the long-term in vivotracing of glial progenitor lineages. Analyses of clonal dispersion inthe adult cortex revealed unanticipated and highly specific clonaldistribution patterns. In addition to the existence of clonal arrange-ments in specific domains, we found that different classes of astro-cytes emerge from different clones. This reinforces the view thatlineage origin impinges on cell heterogeneity, unveiling a new levelof astrocyte diversity likely associated with specific regionalfunctions.Keywords: glia, gliogenesis, lineage, pial, progenitorIntroductionIn the central nervous system, astrocytes represent a hetero-geneous population of cells that fulfill a number ofcomplex functions in the brain, related to both health anddisease (Parpura and Haydon 2009; Garcia-Marques et al.2010; Matyash and Kettenmann 2010; Zhang and Barres2010). These cells originate from different types of progeni-tors (Cameron and Rakic 1991; Marshall et al. 2003; Hoch-stim et al. 2008; reviewed in Hewett 2009), although therelationship between the origin and the heterogeneity ofmature astrocytes is still unclear. Indeed, it is currently diffi-cult to gain a more precise understanding of astrocyte de-velopment due to the absence of suitable in vivoapproaches to trace their lineage (Freeman 2010; Rowitchand Kriegstein 2010).Astrocyte lineage relationships were first described by Cajal(1913) who showed the existence of the isogenic cell groups.More recent studies, partially described the clonal compo-sition of the cortex (Luskin et al. 1988; Price and Thurlow1988; Grove et al. 1993; Noctor et al. 2001; Zerlin et al. 2004),although there is a notable absence of reports in otherregions. Furthermore, it is still unknown how astrocyteclones, composed by cells originated from the same progeni-tor, impact in both the astrocyte heterogeneity and the func-tion. Lineage relationships between cells have been addressedusing a variety of clonal assays mostly based on defectiveretroviral infection where just one progenitor acquires the flu-orescent mark. Howeve, this approach has certain disadvan-tages related to splitting and lumping errors, retroviralsilencing, as well as non-uniform targeting (Petit et al. 2005;Costa et al. 2009). More recent approaches like mosaicanalysis with double markers system (Zong et al. 2005),Brainbow (Livet et al. 2007), Flybow (Hadjieconomou et al.2011; Hampel et al. 2011) or lentiviral RGB (red, green andblue) marking (Weber et al. 2011) have taken advantage ofthe expression of several reporters to trace lineages in vivo.Nevertheless, these techniques rely on the combinedexpression of as many as four reporters and thus, they alsoremain prone to possible epigenetic silencing and splitting/lumping errors. To overcome these problems, we have devel-oped a novel strategy, “Star Track”, to analyze cell lineagesthrough the combinatorial expression of 6 fluorescent pro-teins under the regulation of the GFAP promoter, both in thenucleus and in the cytoplasm. Stochastic expression of these12 fluorescent proteins, after in utero electroporation, pro-duced inheritable marks that permitted the long-term lineageof glial progenitors to be traced in vivo. An exhaustive analy-sis of the adult cortex revealed an unanticipated, specific, andintriguing clonal pattern. In addition to the presence of clonalarrangements of astroglial cells in specific domains, the exist-ence of restricted pial and fibrous clones was particularly no-teworthy. The positional identity of these astrocyte clonesrepresents a new level of astrocyte diversity that may beimportant for their specific regional functions as an individualentity or as part of a functional unit.Materials and Methods
126 citations
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TL;DR: A three-dimensional reconstruction is generated to study the morphological formation of the two ganglionic eminences and the interganglionic sulcus and describes the spatiotemporal sequence of GABA, Calbindin, and Calretinin expression, suggesting that the cells migrating tangentially form a heterogeneous population.
122 citations
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TL;DR: TheOlfactory glomeruli represent morphological and functional units in which olfactory information is processed in specialized synaptic arrangements established between the central processes of sensory neurons and the terminal portions of the dendrites of periglomerular, tufted, and mitral cells.
Abstract: The olfactory glomeruli represent morphological and functional units in which olfactory information is processed in specialized synaptic arrangements established between the central processes of sensory neurons, whose cell bodies are located in the olfactory epithelium, and the terminal (intraglomerular) portions of the dendrites of periglomerular, tufted, and mitral cells. The olfactory glomeruli are surrounded by distinctive glial formations in which the peripheral glia interacts with the central glia. We have studied the morphology and organization of neuroglial cells in the layer of olfactory nerves and the glomerular layer of the olfactory bulb in the insectivorous hedgehog (Erinaceus europaeus) with the electron microscope, Golgi method, and immunohistochemistry by using antibodies to glial fibrillary acidic protein (GFAP) and "rip," a monoclonal antibody that stains oligodendrocytes and their processes in the rat (Friedman et al.: Glia 2:380-390, '89). The peripheral glia is represented by a special category of cells that are closely related to astrocytes and known as sheathing cells. They accompany olfactory axons to their entrance in the glomeruli where they interact with the central glia, represented by astrocytes and oligodendrocytes. The sheathing cells typically display indented nuclei and protoplasmic expansions forming laminar processes wrapping several axons together. Astrocytes surrounding the glomerular neuropil belong to the velate type. They display numerous sheet-like processes enveloping dendritic segments and periglomerular cell bodies. Oligodendrocytes were found surrounding the glomeruli and at the interstices separating different glomeruli. Myelinated dendritic segments and cell bodies were found surrounding the olfactory glomeruli. These myelin coverings probably derive from oligodendrocytes. Together with the astrocytic lamellar expansions, they provide a rigid structural support that contributes to the segregation of group of different cells while remaining relatively isolated from other influences at the periphery of the glomeruli.
121 citations
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TL;DR: This review discusses International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
3,044 citations
01 Jan 1945
2,160 citations
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TL;DR: The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated.
Abstract: Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells—radial glia (RG) in development and specific subpopulations of astrocytes in adult mammals—function as primary progenitors or neural stem cells (NSCs). This is a fundamental departure from classical views separating neuronal and glial lineages early in development. Direct visualization of the behavior of NSCs and lineage-tracing studies reveal how neuronal lineages emerge. In development and in the adult brain, many neurons and glial cells are not the direct progeny of NSCs, but instead originate from transit amplifying, or intermediate, progenitor cells (IPCs). Within NSCs and IPCs, genetic programs unfold for generating the extraordinary diversity of cell types in the central nervous system. The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated. Identification of NSCs and IPCs is critical to understand brain development and adult neurogenesis and to develop new strategies for brain repair.
2,118 citations
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TL;DR: It is shown here that neurons are generated in two proliferative zones by distinct patterns of division, and newborn neurons do not migrate directly to the cortex; instead, most exhibit four distinct phases of migration, including a phase of retrograde movement toward the ventricle before migration to the cortical plate.
Abstract: Precise patterns of cell division and migration are crucial to transform the neuroepithelium of the embryonic forebrain into the adult cerebral cortex. Using time-lapse imaging of clonal cells in rat cortex over several generations, we show here that neurons are generated in two proliferative zones by distinct patterns of division. Neurons arise directly from radial glial cells in the ventricular zone (VZ) and indirectly from intermediate progenitor cells in the subventricular zone (SVZ). Furthermore, newborn neurons do not migrate directly to the cortex; instead, most exhibit four distinct phases of migration, including a phase of retrograde movement toward the ventricle before migration to the cortical plate. These findings provide a comprehensive and new view of the dynamics of cortical neurogenesis and migration.
2,062 citations
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TL;DR: The effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders are reviewed and could provide new therapeutic strategies against dysfunctions of glutamatergic transmission.
Abstract: NMDA receptors (NMDARs) are glutamate-gated ion channels and are crucial for neuronal communication. NMDARs form tetrameric complexes that consist of several homologous subunits. The subunit composition of NMDARs is plastic, resulting in a large number of receptor subtypes. As each receptor subtype has distinct biophysical, pharmacological and signalling properties, there is great interest in determining whether individual subtypes carry out specific functions in the CNS in both normal and pathological conditions. Here, we review the effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders. Understanding the rules and roles of NMDAR diversity could provide new therapeutic strategies against dysfunctions of glutamatergic transmission.
1,918 citations