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Neuronal Polarity: Establishment and Maintenance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455171 Year: Pages: 172 DOI: 10.3389/978-2-88945-517-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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The term polarity in a biological context is used to describe an asymmetry in morphology and distribution of molecules. In neurons, their complex shape with typically one axon and several dendrites reflects this asymmetry. Although neurons assume many different shapes and sizes they always maintain these two domains, which are essential for neuronal function. In the most simple view, neurons use their axon to transmit signals over long distances due to its capacity to extend to enormous lengths. Dendrites, on the other hand, are shorter and receive and integrate signals from different locations. The selection of the site where the axon and dendrites initially emerge during embryonic development is a tightly regulated event, eventually important for the correct formation of neuronal circuits, and disturbances of these processes can have pathological consequences due to circuit malformation. An important question is which mechanisms neurons utilize to specify the sites where axonal and dendrite outgrowth occurs and how their identities are maintained during and after development. The formation of these functionally diverse domains is the result of polarized differences of membrane and protein delivery, mitochondria transport, actin dynamics and microtubule stability. However how and in which temporal order all those events which coordinate the selection and maintenance of axons and dendrites is still under investigation. This selection of articles shall highlight new findings, which help to unravel all molecular and cellular events important for neuronal polarity establishment and maintenance.

Never-resting microglia: physiological roles in the healthy brain and pathological implications

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193691 Year: Pages: 172 DOI: 10.3389/978-2-88919-369-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic reviewed the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic discussed the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the regulation of adult neurogenesis as well as hippocampal learning and memory; among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic also summarized the current view of microglial nomenclature, phenotypes, origin and differentiation, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state have been discussed. In conclusion, this Research Topic sought to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Building the gateway to consciousness - about the development of the thalamus

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194704 Year: Pages: 107 DOI: 10.3389/978-2-88919-470-4 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Since years, patterning and function of some brain parts such as the cortex in the forebrain and the optical tectum or cerebellum in the midbrain/hindbrain region are under strong investigation. Interestingly the diencephalon located in the caudal forebrain has been ignored for decades. Consequently, the existing knowledge from the development of this region to function in the mature brain is very fragmented. The central part of the diencephalon is the thalamus. This central relay station plays a crucial role in distributing incoming sensory information to appropriate regions of the cortex. The thalamus develops in the posterior part of the embryonic forebrain, where early cell fate decisions are controlled by local signaling centers. In this Research Topic we discuss recent achievements elucidating thalamic neurogenesis - from neural progenitor cells to highly specialized neurons with cortical target cells in great distance. In parallel, we highlight developmental aspects leading from the early thalamic anlage to the late the organization of the complex relay station of the brain.

Morphogens in the wiring of the nervous system

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197811 Year: Pages: 238 DOI: 10.3389/978-2-88919-781-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Neuronal function relies on the establishment of proper connections between neurons and their target cells during development. This basic statement involves several cellular processes, such as neuronal differentiation, the polarized outgrowth of axons and dendrites from differentiated neurons, and the pathfinding of axons towards target cells. The subsequent recognition of complementary synaptic partners finally triggers the formation, maturation, and maintenance of functional synapses. Morphogens are secreted signaling molecules commanding tissue patterning and cell identity during early embryonic development. Remarkably, growing evidence over the last years arising from different invertebrate and vertebrate model organisms has shown that, after cell fate has been established, morphogens also control the precise wiring and function in the developing and mature nervous system. Accordingly, dysfunctions of the signaling pathways activated by these molecules contribute to synaptic disassembly and altered function in diseases affecting the nervous system. We consider it timely to bring together cumulative evidence pointing to crucial roles for signaling activated by different morphogens in the establishment of precise contacts between neurons and their synaptic partners. Therefore, this research topic issue combines review and research articles aimed to cover the functional relevance of such morphogens on the different steps involved in synaptic assembly and function. Diverse model systems of physiological or pathological conditions have been included, as well as different cellular, biochemical and molecular approaches. Altogether, they contribute in different and complementary ways to build a holistic view of the roles that early development morphogens play during the assembly, maintenance and/or regeneration of functional synapses.

Keywords

Morphogens --- Nervous System --- synapse --- Neurogenesis --- neurodegeneration --- Wnt --- BMP --- Shh

Structure, function, and plasticity of hippocampal dentate gyrus microcircuits

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193875 Year: Pages: 133 DOI: 10.3389/978-2-88919-387-5 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time. How are these unique functions implemented at the level of cells and synapses? Dentate gyrus granule cells receive excitatory neuron input from the entorhinal cortex and send excitatory output to the hippocampal CA3 region via the mossy fibers. Furthermore, several types of GABAergic interneurons are present in this region, providing inhibitory control over granule cell activity via feedback and feedforward inhibition. Additionally, hilar mossy cells mediate an excitatory loop, receiving powerful input from a small number of granule cells and providing highly distributed excitatory output to a large number of granule cells. Finally, the dentate gyrus is one of the few brain regions exhibiting adult neurogenesis. Thus, new neurons are generated and functionally integrated throughout life. How these specific cellular and synaptic properties contribute to higher brain functions remains unclear. One way to understand these properties of the dentate gyrus is to try to integrate experimental data into models, following the famous Hopfield quote: "Build it, and you understand it." However, when trying this, one faces two major challenges. First, hard quantitative data about cellular properties, structural connectivity, and functional properties of synapses are lacking. Second, the number of individual neurons and synapses to be represented in the model is huge. For example, the dentate gyrus contains ~1 million granule cells in rodents, and ~10 million in humans. Thus, full scale models will be complex and computationally demanding. In this Frontiers Research Topic, we collect important information about cells, synapses, and microcircuit elements of the dentate gyrus. We have put together a combination of original research articles, review articles, and a methods article. We hope that the collected information will be useful for both experimentalists and modelers. We also hope that the papers will be interesting beyond the small world of "dentology", i.e., for scientists working on other brain areas. Ideally, the dentate gyrus may serve as a blueprint, helping neuroscientists to define strategies to analyze network organization of other brain regions.

Mechanisms of Neuronal Migration during Corticogenesis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198863 Year: Pages: 183 DOI: 10.3389/978-2-88919-886-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-01-19 14:05:46
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The cerebral cortex plays central roles in many higher-order functions such as cognition, language, consciousness, and the control of voluntary behavior. These processes are performed by the densely interconnected networks of excitatory pyramidal neurons and inhibitory interneurons, and the balanced development of these two types of neuron is quite important. During cortical development, pyramidal neurons and interneurons show quite different migratory behaviors: radial migration and tangential migration, respectively. Pyramidal neurons are generated in the ventricular zone of the dorsal telencephalon, and migrate radially along radial glial fibers toward the pial surface, forming a six-layered cortical structure in an “ inside-out” manner. On the other hand, cortical interneurons are generated in the medial and caudal ganglionic eminence in the ventral telencephalon, and follow long tangential migratory paths into the cortex. Defects in these migration processes result in abnormalities in the cortical layer structure and neuronal networks, which may cause various neurological and psychiatric conditions such as epilepsy and schizophrenia. Accordingly, besides basic scientific interest, elucidation of the mechanism of neuronal migration is essential for understanding the pathogenesis of these diseases. This Research Topic includes a series of articles ranging from the basic mechanism of neocortical development to the malformation and evolution of the neocortex. We do hope that the present ebook will further stimulate the interest in the fascinating investigations of neuronal migration and corticogenesis.

In vivo Cell Biology of Cerebral Cortical Development and Its Related Neurological Disorders: Cellular Insights into Neurogenesis and Neuronal Migration

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199624 Year: Pages: 268 DOI: 10.3389/978-2-88919-962-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-01-19 14:05:46
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The brain consists of a complex but precisely organized neural network, which provides the structural basis of higher order functions. Such a complex structure originates from a simple pseudostratified neuroepithelium. During the developing mammalian cerebral cortex, a cohort of neural progenitors, located near the ventricle, differentiates into neurons and exhibits multi-step modes of migration toward the pial surface. Tight regulation of neurogenesis and neuronal migration is essential for the determination of the neuron number in adult brains and the proper positioning of excitatory and inhibitory neurons in a specific layer, respectively. In addition, defects in neurogenesis and neuronal migration can cause several neurological disorders, such as microcephaly, periventricular heterotopia and lissencephaly. Recent advances in genetic approaches to study the developing cerebral cortex, as well as the use of a number of novel techniques, particularly in vivo electroporation and time-lapse analyses using explant slice cultures, have significantly increased our understanding of cortical development. These novel techniques have allowed for cell biological analyses of cerebral cortical development in vivo or ex vivo, showing that many cellular events, including endocytosis, cell adhesion, microtubule and actin cytoskeletal regulation, neurotransmitter release, stress response, the consequence of cellular crowding (physical force), dynamics of transcription factors, midbody release and polarity transition are required for neurogenesis and/or neuronal migration. The aim of this research topic is to highlight molecular and cellular mechanisms underlying cerebral cortical development and its related neurological disorders from the cell biological point of views, such as cell division, cell-cycle regulation, cytoskeletal organization, cell adhesion and membrane trafficking. The topic has been organized into three chapters: 1) neurogenesis and cell fate determination, 2) neuronal migration and 3) cortical development-related neurological disorders. We hope that the results and discussions contributed by all authors in this research topic will be broadly useful for further advances in basic research, as well as improvements in the etiology and care of patients suffering from neurological and psychiatric disorders.

Stem cells and progenitor cells in ischemic stroke - fashion or future?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197248 Year: Pages: 156 DOI: 10.3389/978-2-88919-724-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Stroke remains one of the most devastating diseases in industrialized countries. Recanalization of the occluded arterial vessel using thrombolysis is the only causal therapy available. However, thrombolysis is limited due to severe side effects and a limited time window. As such, only a minority of patients receives this kind of therapy, showing a need for new and innovative treatment strategies. Although neuroprotective drugs have been shown to be beneficial in a variety of experimental stroke models, they ultimately failed in clinical trials. Consequently, recent scientific focus has been put on modulation of post-ischemic neuroregeneration, either via stimulation of endogenous neurogenesis or via application of exogenous stem cells or progenitor cells. Neurogenesis persists within the adult brain of both rodents and primates. As such, neural progenitor cells (NPCs) are found within distinct niches like the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus. Cerebral ischemia stimulates these astrocyte-like progenitor cells, upon which NPCs proliferate and migrate towards the site of lesion. There, NPCs partly differentiate into mature neurons, without significantly being integrated into the residing neural network. Rather, the majority of new-born cells dies within the first weeks post-stroke, leaving post-ischemic neurogenesis a phenomenon of unknown biological significance. Since NPCs do not replace lost brain tissue, beneficial effects observed in some studies after either stimulated or protected neurogenesis are generally contributed to indirect effects of these new-born cells. The precise identification of appropriated cellular mediators, however, is still elusive. How do these mediators work? Are they soluble factors or maybe even vesicular structures emanating from NPCs? What are the cues that guide NPCs towards the ischemic lesion site? How can post-ischemic neurogenesis be stimulated? How can the poor survival of NPCs be increased? In order to support post-ischemic neurogenesis, a variety of research groups have focused on application of exogenous stem/progenitor cells from various tissue sources. Among these, cultivated NPCs from the SVZ and mesenchymal stem cells (MSCs) from the bone marrow are frequently administered after induction of stroke. Although neuroprotection after delivery of stem/progenitor cells has been shown in various experimental stroke models, transplanted cells are usually not integrated in the neural network. Again, the vast amount of grafted cells dies or does not reach its target despite profound neuroprotection, also suggesting indirect paracrine effects as the cause of neuroprotection. Yet, the factors being responsible for these observations are under debate and still have to be addressed. Is there any “optimal” cell type for transplantation? How can the resistance of grafted cells against a non-favorable extracellular milieu be increased? What are the molecules that are vital for interaction between grafted cells and endogenous NPCs? The present research topic seeks to answer - at least in part - some of the aforementioned questions. Although the research topic predominantly focuses on experimental studies (and reviews alike), a current outlook towards clinical relevance is given as well.

Cell and molecular signaling, and transport pathways involved in growth factor control of synaptic development and function

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196432 Year: Pages: 112 DOI: 10.3389/978-2-88919-643-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-08-16 10:34:25
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Brain derived neurotophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) signaling has been extensively studied for its roles in the central nervous system (CNS) ranging from cell survival, axonal and dendritic growth and synapse formation. Intracellular signaling pathways triggered by BDNF activate gene transcription, translation, post-translational functions, trafficking of key synaptic proteins, and synaptic release mechanism. BDNF-TrkB signaling mediates long-lasting activity-modulated synaptic changes on excitatory and inhibitory neurons and plays significant roles in circuit development and modulation. Furthermore, this pathway is critical for learning, memory, sensory processing and other cognitive functions, and is implicated in neurological and psychiatric diseases. In addition to BDNF, more recent studies have identified new “growth” factors that play important roles in the development, maturation and maintenance and modulation of synaptic function. However, details of the cytoplamic signaling systems downstream of these synaptogenic factors are often less understood than conventional neurotophin signaling. This e-Book has collected original studies and review articles that present cellular and molecular mechanisms concerning activity-dependent synapse formation and their implications for behavior and brain disorders. It is our hope that readers will perceive this volume as a showcase for diversity and complexity of synaptogenic growth factors, and will stimulate further studies in this field.

CNS Recovery after Structural and/or Physiological/Psychological Damage

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450404 Year: Pages: 107 DOI: 10.3389/978-2-88945-040-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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There is an assumption that environmental threats could cause important damages in central nervous system. As a consequence, several forms of brain structural plasticity could be affected. The environmentally mediated risks include generally physical (such as brain and spinal cord injury) and psychological / psychosocial influences (e.g. stress). In general, the response of the organism to these environmental challenges passes via adaptive responses to maintain homeostasis or functional recovery. These processes engage the immune system, the autonomic nervous system (ANS) besides the hypothalamo-hypophyseo-adrenal (HPA) axis via specific hormones, neurotransmitters, neuropeptides and other factors which participate, in several cases, in structural remodeling in particular brain areas. To what extent a brain and / or spinal cord recovery after structural and / or physiological / psychological damage could occur and by which mechanisms, this is the goal of this Research Topic. It concerns neurogenesis, growth factors and their receptors, and morphological plasticity. On the other hand, it is well known that stress experienced an obvious impact on many behavioral and physiological aspects. Thus, environmental stress affects neuroendocrine structure and function and hence such aspects may influence brain development. Knowing normal organization of neurotensin receptors’ system during postnatal development in human infant will help understanding the dysfunction of this neuropetidergic system in “sudden infant syndrome” victims. Stress could affect also other non-neuroendocrine regions and systems. GABA is one of the classical neurotransmitter sensitive to stress either when applied acutely or repetitively as well as its receptor GABAA. Furthermore, the modulation of this receptor complex notably by neurosteroids is also affected by acute stress. These steroids seem to play a role in the resilience retained by the stressed brain. Their modulatory role will be studied in the context of chronic stress in rats. Finally, one of the major impacts of stress besides changes in psychological behavior is the alteration of food intake control causing in final eating disorders. This alteration is the result of changes occurring in activity of brain regions involved in stress responses (principally HPA and ANS) and which are also involved in food intake control. The series of studies presented here, will try to explain how different stress paradigms affect this function and the eventual interactions of glucocorticoids with orexigenic (neuropetide Y: NPY/Agouti Related Peptide: AgRP) and anorexigenic peptides (Pre-opiomelanocortin peptide: POMC/Cocaine Amphetamine regulatory Transcript peptide: CART).

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