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Regulatory RNAs in the Nervous System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194834 Year: Pages: 344 DOI: 10.3389/978-2-88919-483-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-11-16 15:44:59
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Until about a decade ago, the non-coding part of the genome was considered without function. RNA sequencing studies have shown, however, that a considerable part of the non-coding genome is transcribed and that these non-coding RNAs (nc-RNAs) can regulate gene expression. Almost on weekly basis, new findings reveal the regulatory role of nc-RNAs exert in many biological processes. Overall, these studies are making increasingly clear that, both in model organisms and in humans, complexity is not a function of the number of protein-coding genes, but results from the possibility of using combinations of genetic programs and controlling their spatial and temporal regulation during development, senescence and in disease by regulatory RNAs. This has generated a novel picture of gene regulatory networks where regulatory nc-RNAs represent novel layers of regulation. Particularly well-characterized is the role of microRNAs (miRNAs), small nc-RNAs, that bind to mRNAs and regulate gene expression after transcritpion. This message is particularly clear in the nervous system, where miRNAs have been involved in regulating cellular pathways controlling fundamental functions during development, synaptic plasticity and in neurodegenerative disease. It has also been shown that neuronal miRNAs are tightly regulated by electrical activity at the level of transcription, biogenesis, stability and specifically targeted to dendrites and synapsis. Deregulation of expression of miRNAs is proposed not only as potential disease biomarker, but it has been implicated directly in the pathogenesis of complex neurodegenerative disease. This so-called RNA revolution also lead to the exploitation of RNA interference and the development of related tools as potential treatment of a vast array of CNS disease that could benefit from regulation of disease-associated genes. In spite of these advancements, the relatively young age of this field together with the inherent high molecular complexity of RNA regulation of biological processes have somewhat hindered its communication to the whole of the neuroscience community. This Research Topic aims at improving this aspect by putting around the same virtual table scientists covering aspects ranging from basic molecular mechanisms of regulatory RNAs in the nervous system to the analysis of the role of specific regulatory RNAs in neurobiological processes of development, plasticity and aging. Furthermore, we will welcome papers analyzing the role of regulatory RNAs in disease models from neuromuscular to higher cognitive functions, and we will also encourage submission of more technically oriented papers dealing with new methodologies to study regulatory RNA biology and its translational potential.

Neuronal and glial structural plasticity induced by drugs of abuse

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195985 Year: Pages: 90 DOI: 10.3389/978-2-88919-598-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-03-10 08:14:32
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Drugs of abuse induce a host of alterations in brain structure and function, ranging from changes in gene expression and epigenetic processes to aberrant synaptic plasticity to volumetric changes in discrete brain regions. These alterations can be drug class-specific, and are not confined to neurons, as drugs of abuse also induce molecular and cellular alterations in various glial cell types such as astrocytes and microglia. The phenomenon of drug-induced plasticity includes changes in dendritic branching and architecture, dendritic spine density and morphology, astrocyte-neuronal interactions, dysregulation of glutamatergic and GABAergic signaling, and alterations in myelination or microglial phenotype. This drug-induced "rewiring" of the brain at numerous levels can contribute to the development, maintenance, and persistence of the addicted state, as well as associated deficits in normal cognitive functioning. The aim of this Research Topic is to collect recent and important findings related to the structural alterations produced by drug of abuse in neurons, glial, and other cell types of the central nervous system.

Keywords

plasticity --- Dendrite --- Spine --- Glutamate --- Dopamine --- GABA --- Neuron --- glia --- astrocyte --- Addiction

A Multidisciplinary Approach to Motor Learning and Sensorimotor Adaptation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193653 Year: Pages: 214 DOI: 10.3389/978-2-88919-365-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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The plasticity of the living matter of our nervous system, in short, is the reason why we do a thing with difficulty the first time, but soon do it more and more easily, and finally, with sufficient practice, do it semi-mechanically, or with hardly any consciousness at all. William James, 1899. It is over 100 years since James described the acquisition of skill. How much, or how little, have recent advances in science changed the way we think about skill learning? What theories and ideas do we still hold dear and which have we discarded? Advances in neuroimaging over the past 20 years have provided insight into the dynamic neural processes underlying human motor skill acquisition, focusing primarily on brain networks that are engaged during early versus late stages of learning. What has been challenging for the field is to tightly link these shifting neural processes with what is known about measureable behavioral changes and strategic processes that occur during learning. The complex nature of behavior and strategy in motor learning often result in a trade-off between experimental control and external validity. The articles assembled for this special issue cut across a number of related disciplines and investigate skill learning across multiple domains. The broad range of theoretical, analytical and methodological approaches offer complementary approaches that can be exploited to develop integrated models of skilled learning. It is our hope that this collection inspires innovation and collaboration amongst researchers, and thereby, accelerates development of societally relevant translational paradigms.

Plasticity of primary afferent neurons and sensory processing after spinal cord injury

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193967 Year: Pages: 221 DOI: 10.3389/978-2-88919-396-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2015-12-03 13:02:24
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Traumatic injury of the spinal cord affects the entire organism directly and indirectly. Primary injury destroys neurons and severs axons which participate in neural circuits. Secondary injuries and pathologies arise from numerous sources including systemic inflammation, consequential damage of cutaneous, muscular, and visceral tissues, and dysregulation of autonomic, endocrine and sensory- motor functions. Evidence is mounting that spinal cord injury (SCI) affects regions of the nervous system spatially remote from the injury site, as well as peripheral tissues, and alters some basic characteristics of primary afferent cell biology and physiology (cell number, size/frequency, electrophysiology, other). The degree of afferent input and processing above the lesion is generally intact, while that in the peri-lesion area is highly variable, though pathologies emerge in both regions, including a variety of pain syndromes. Primary afferent input to spinal regions below the injury and the processing of this information becomes even more important in the face of complete or partial loss of descending input because such spared sensory processing can lead to both adaptive and pathological outcomes. This issue hosts review and research articles considering mechanisms of plasticity of primary afferent neurons and sensory processing after SCI, and how such plasticity contributes to sparing and/or recovery of functions, as well as exacerbation of existing and/or emergent pathologies. A critical issue for the majority of the SCI community is chronic above-, peri-, and below-level neuropathic pain, much of which may arise, at least in part, from plasticity of afferent fibers and nociceptive circuitry. For example, autonomic dysreflexia is common hypertensive syndrome that often develops after SCI that is highly reliant on maladaptive nociceptive sensory input and processing below the lesion. Moreover, the loss of descending input leaves the reflexive components of bladder/bowel/sexual function uncoordinated and susceptible to a variety of effects through afferent fiber plasticity. Finally, proper afferent feedback is vital for the effectiveness of activity-dependent rehabilitative therapies, but aberrant nociceptive input may interfere with these approaches since they are often unchecked due to loss of descending modulation.

Recent insights into perceptual and motor skill learning (The computational and neural substrates of skill learning)

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194469 Year: Pages: 132 DOI: 10.3389/978-2-88919-446-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Improvements in task performance following practice can occur as a result of changes in distinct cognitive and neural processes. In some cases, we can improve our performance by selecting a more successful behavior that is already part of our available repertoire. Skill learning, on the other hand, refers to a slower process that results in improving the ability to perform a behavior, i.e., it involves the acquisition of a behavior that was not available to the controller before training. Skill learning can take place both in the sensory and in the motor domains. Sensory skill acquisition in perceptual learning tasks is measured by improvements in sensory acuity through practice-induced changes in the sensitivity of relevant neural networks. Motor skill is harder to define as the term is used whenever a motor learning behavior improves along some dimension. Nevertheless, we have recently argued that as in perceptual learning, acuity is an integral component in motor skill learning. In this special topic we set out to integrate experimental and theoretical work on perceptual and motor skill learning and to stimulate a discussion regarding the similarities and differences between these two kinds of learning.

Autism Spectrum Disorders: From genotypes to phenotypes

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196807 Year: Pages: 93 DOI: 10.3389/978-2-88919-680-7 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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This Research Topic covers the pathogenetic processes in Autism Spectrum Disorder (ASD) that underpin the translation of genetic vulnerability to clinically significant symptoms. Available research data in ASD suggests that it is a neural connectivity disorder and that the social communication and related neurobehavioural symptoms result from reduced synchronization between key "social brain" regions. These interconnected neural systems can be understood through the relationship between functionally relevant anatomic areas and neurochemical pathways, the programming of which are genetically modulated during neurodevelopment and mediated through a range of epigenetic and environmental modulators. Elucidating the underlying molecular mechanisms can provide an invaluable window for understanding the neural wiring that regulates higher brain functions and consequent clinical phenotypes. In keeping with the multi modal and diverse origins of ASD, this Research Topic explores the genetic underpinnings and environmental modulation in the aetiology; neural substrates, biomarkers and endophenotypes that underlie clinical characteristics; as well as neurochemical pathways and pathophysiological mechanisms that pave the way for therapeutic interventions. Furthermore, since genetically mediated deficits and consequent functional impairments involve activity-dependent synapse development that depends on postnatal learning and experience, the trajectory towards the final clinical expression could be modulated by early interventions that exploit the neuronal maturation and brain plasticity. However, identifying these diverse pathogenetic processes and tailoring interventions would require subtyping ASD into homogeneous subgroups. In this regard, this topic covers the current state of evidence in the literature through topic reviews as well as ongoing original work that provides tangible hypotheses and directions for future research.

The Role of Glia in Plasticity and Behavior

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196906 Year: Pages: 104 DOI: 10.3389/978-2-88919-690-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Glial cells are no longer considered passive bystanders in neuronal brain circuits. Not only are they required for housekeeping and brain metabolism, they are active participants in regulating the physiological function and plasticity of brain circuits and the online control of behavior both in invertebrate and vertebrate model systems. In invertebrates, glial cells are essential for normal function of sensory organs (C. elegans) and necessary for the circadian regulation of locomotor activity (D. melanogaster). In the mamallian brain, astrocytes are implicated in the regulation of cortical brain rhythms and sleep homeostasis. Disruption of AMPA receptor function in a subset of glial cell types in mice shows behavioral deficits. Furthermore, genetic disruption of glial cell function can directly control behavioral output. Regulation of ionic gradients by glia can underlie bistability of neurons and can modulate the fidelity of synaptic transmission. Grafting of human glial progenitor cells in mouse forebrain results in human glial chimeric mice with enhanced plasticity and improved behavioral performance, suggesting that astrocytes have evolved to cope with information processing in more complex brains. Taken together, current evidence is strongly suggestive that glial cells are essential contributors to information processing in the brain. This Research Topic compiles recent research that shows how the molecular mechanisms underlying glial cell function can be dissected, reviews their impact on plasticity and behavior across species and presents novel approaches to further probe their function.

Keywords

glia --- Astrocytes --- plasticity --- Behavior --- Gq --- DREADD --- C. elegans --- Hippocampus --- Cerebellum --- Cortex

Cellular and Phenotypic Plasticity in Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196623 Year: Pages: 77 DOI: 10.3389/978-2-88919-662-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2016-08-16 10:34:25
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The process of Epithelial-Mesenchymal-Transition (EMT) is known to result in a phenotype change in cells from a proliferative state to a more invasive state. EMT has been reported to drive the metastatic spread of various cancers and has also been associated with drug resistance to cytotoxics and targeted therapeutics. Recently phenotype switching akin to EMT has been reported in non-epithelial cancers such as metastatic melanoma. This process involves changes in EMT-Transcription Factors (EMT-TFs), suggesting that phenotype-switching may be common to several tumour types. It remains unclear as to whether the presence of both Epilthelial-like and Mesenchymal-like cells are a pre-requisite for phenotype switching within a tumour, how this heterogeneity is regulated, and if alteration of cell phenotype is sufficient to mediate migratory changes, or whether drivers of cell migration result in an associated phenotype switch in cancer cells. Similarly it has yet to be clarified if cells in an altered phenotype can be refractory to drug therapy or whether mediators of drug resistance induce a concurrent phenotypic change. Little is known today about the underlying genetic, epigenetic and transient changes that accompany this phenotypic switch and about the role for the tumor micro-environment in influencing it. Hence this is currently an area of speculation and keen interest in the Oncology field with wide-ranging translational implications. In this Frontiers Research Topic, we discuss our current understanding of these concepts in various cancer types including breast cancer, colorectal cancer and metastatic melanoma. This topic covers how these processes of cellular and phenotypic plasticity are regulated and how they relate to cancer initiation, progression, dormancy, metastases and response to cytotoxics or targeted therapies.

Inhibitory Function in Auditory Processing

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196678 Year: Pages: 231 DOI: 10.3389/978-2-88919-667-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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There seems little doubt that from the earliest evolutionary beginnings, inhibition has been a fundamental feature of neuronal circuits - even the simplest life forms sense and interact with their environment, orienting or approaching positive stimuli while avoiding aversive stimuli. This requires internal signals that both drive and suppress behavior. Traditional descriptions of inhibition sometimes limit its role to the suppression of action potential generation. This view fails to capture the vast breadth of inhibitory function now known to exist in neural circuits. A modern perspective on inhibitory signaling comprises a multitude of mechanisms. For example, inhibition can act via a shunting mechanism to speed the membrane time constant and reduce synaptic integration time. It can act via G-protein coupled receptors to initiate second messenger cascades that influence synaptic strength. Inhibition contributes to rhythm generation and can even activate ion channels that mediate inward currents to drive action potential generation. Inhibition also appears to play a role in shaping the properties of neural circuitry over longer time scales. Experience-dependent synaptic plasticity in developing and mature neural circuits underlies behavioral memory and has been intensively studied over the past decade. At excitatory synapses, adjustments of synaptic efficacy are regulated predominantly by changes in the number and function of postsynaptic glutamate receptors. There is, however, increasing evidence for inhibitory modulation of target neuron excitability playing key roles in experience-dependent plasticity. One reason for our limited knowledge about plasticity at inhibitory synapses is that in most circuits, neurons receive convergent inputs from disparate sources. This problem can be overcome by investigating inhibitory circuits in a system with well-defined inhibitory nuclei and projections, each with a known computational function. Compared to other sensory systems, the auditory system has evolved a large number of subthalamic nuclei each devoted to processing distinct features of sound stimuli. This information once extracted is then re-assembled to form the percept the acoustic world around us. The well-understood function of many of these auditory nuclei has enhanced our understanding of inhibition's role in shaping their responses from easily distinguished inhibitory inputs. In particular, neurons devoted to processing the location of sound sources receive a complement of discrete inputs for which in vivo activity and function are well understood. Investigation of these areas has led to significant advances in understanding the development, physiology, and mechanistic underpinnings of inhibition that apply broadly to neuroscience. In this series of papers, we provide an authoritative resource for those interested in exploring the variety of inhibitory circuits and their function in auditory processing. We present original research and focused reviews touching on development, plasticity, anatomy, and evolution of inhibitory circuitry. We hope our readers will find these papers valuable and inspirational to their own research endeavors.

Ca2+ and Ca2+-interlocked Membrane Guanylate Cyclase Modulation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195060 Year: Pages: 185 DOI: 10.3389/978-2-88919-506-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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The tale of cyclic GMP has been astonishing. Having overcome an initial disbelief, cyclic GMP has risen to its present eminence as a premium cellular signal transduction messenger of not only hormonal extracellular but also of the intracellular signals. This research topic focuses on the pathways and functions of membrane guanylate cyclases in different tissues of the body and their interplay with intracellular sensory signals where in many cases, cyclic GMP along with Ca2+ have taken on roles as synarchic co-messengers.

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