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The Transcriptional Regulation of Memory

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198658 Year: Pages: 116 DOI: 10.3389/978-2-88919-865-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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The formation of various forms of memory involves a series of distinct cellular and molecular mechanisms, many of which are not fully understood. There are highly conserved pathways that are involved in learning, memory, and synaptic plasticity, which is the primary substrate for memory storage. The formation of short-term (across minutes) memory is mediated by local changes in synapses, while long-term (across hours to days) memory storage is associated with activation of transcription and synthesis of proteins that modify synaptic function. Transcription factors, which can either repress or activate transcription, play a vital role in driving protein synthesis underlying synaptic plasticity and memory, whereby protein synthesis provides the necessary building blocks to accommodate structural changes at the synapse that foster memory formation. Recent data implicate several families of transcription factors that appear critically important in the regulation of memory.In this Topic we will focus on the families of transcription factors thus far found to be critically involved in synaptic plasticity and memory formation. These include cAMP response element binding protein (CREB), Rel/nuclear factor B (Rel/NFB), CCAAT enhancer binding protein (C/EBP), and early growth response factor (Egr). In recent years, numerous studies have implicated epigenetic mechanisms, changes in gene activity and expression that occur without alteration in gene sequence, in the memory consolidation process. DNA methylation and chromatin remodeling are critically involved in learning and memory, supporting a role of epigenetic mechanisms. Here we provide more evidence of the importance of DNA methylation, histone posttranslational modifications and the role of histone acetylation and HDAC inhibitors in above mentioned processes.

Ionotropic Glutamate Receptors Trafficking in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450893 Year: Pages: 141 DOI: 10.3389/978-2-88945-089-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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The knowledge about the properties and importance of ionotropic glutamate receptor trafficking is ever increasing. Importantly, the pace of the progress has been accelerated in recent years. Here, our contributors provide a) reviews on specific topics that present an up-to-date overview of the field, as well as b) original articles with the relevant new findings.

Neuroplasticity and Extracellular Proteolysis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198511 Year: Pages: 151 DOI: 10.3389/978-2-88919-851-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Neuroplasticity refers to the ability of the Central Nervous System (CNS) to alter its structure and function in response to a variety of physiological and pathological processes such as development, cognition, injury or neurological diseases. Since more than four decades, studies on synaptic plasticity in the context of memory and learning attracted a remarkable interest. Soon after first seminal works on synaptic plasticity were published, research in this field was extended by studies on non-synaptic as wells as structural plasticity towards a goal to understand cellular and molecular determinants of cognition. Over the past two decades, yet two additional crucial players in neuroplastic phenomena started to be intensely investigated – glial cells and the extracellular matrix (ECM). Growing awareness that glial cells, especially astrocytes, are important regulators of synaptic functions gave rise to a novel concept of a tri-partite synapse. Also, over the last two decades, a growing body of evidence has accumulated that the extracellular matrix (ECM) in the brain is strongly involved in regulation of neurons, in particular, in synaptic plasticity. Thus, a concept of tetra-partite synapse was put forward by some neuroscientists. The cross-talk between neuron-glia-ECM system involves enzymatic degradation of proteins or peptides and amino acids occurring in each of these brain constituents by means of a variety of proteases. Importantly, it has been realized that proteases such as serine proteases and matrix metalloproteinases, not only accompany “robust” phenomena such as cell division, or development or neurodegnerative conditions but may play a very subtle signaling functions, particularly important in memory acquisition. Indeed, the repertoire of substrates for these enzymes covers a wide variety of proteins known to play important role in the neuroplastic phenomena (e.g. BDNF, TNF-a, ephrin systems, various cell adhesion molecules, etc.). In result, the role of metalloproteinases and such serine proteases as tissue plasminogen activator (tPA), neuropsin or neurotrypsin in synaptic plasticity as well as in learning and memory has been particularly well demonstrated. It needs to be emphasized, however, that in spite of a remarkable progress in this field, several basic questions regarding molecular and cellular mechanisms remain unanswered. Potential involvement of so many important players (various proteases and their substrates in neurons, glia and in ECM) points to an enormous potential for plasticity phenomena but makes also studies into underlying mechanisms particularly difficult. In the proposed Research Topic we provide both review of the current state of the art and present some original reports on specific aspects of the role of proteolysis in neuroplasticity phenomena. The present ebook starts with extensive reviews describing involvement of proteolysis not only in synaptic plasticity but also in regulating endogenous excitability and structural changes at the network, cellular and subcellular levels. Cross-talk between neuroplasticity and proteolysis is also emphasized in the context of development and in relation to various pathologies. Whereas in the first part of the present ebook, the major focus is on metalloproteinases, the successive articles address the role of neuropsin and thrombin. The Research Topic is concluded with a series of articles describing the components of extracellular matrix and adhesion proteins and their elaboration by mechanisms dependent directly or indirectly on proteolysis. We do hope that the present ebook will further stimulate the interest in the fascinating investigations into neuroplasticity-proteolysis cross-talk.

Ubiquitin and the Brain: Roles of Proteolysis in the Normal and Abnormal Nervous System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452859 Year: Pages: 241 DOI: 10.3389/978-2-88945-285-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Proteolysis by the ubiquitin-proteasome pathway (UPP) in the nervous system has been extensively studied both in the context of normal physiological function as well as abnormal pathological conditions. Although ubiquitin was used as a marker of brain pathology, the normal functions of the UPP were not studied much in the nervous system until the 1990s. The early investigations focused on synaptic plasticity which was followed by studies on the roles of protein degradation in the development of the nervous system. Research on the role of abnormal roles of the UPP follows a parallel trajectory. Since the 2000s, the field has grown to encompass many subareas of research and several model systems. Despite the progress made, many unanswered questions still remain. For example, there are many unknowns about the precise spatial and temporal control of protein degradation in the normal nervous system. With respect to the roles of proteolysis in brain pathology a major challenge is to elucidate the connection between impaired protein degradation and disease progression. In addition, in-depth studies of the roles of ubiquitin-proteasome-mediated proteolysis in neurodegenerative diseases are promising in identifying therapeutic targets. This ebook contains original research papers and insightful reviews that cover several aspects of proteolysis by the UPP and its physiological as well as pathological functions in the nervous system.

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.

Synaptic Plasticity in Neuromorphic Systems

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198771 Year: Pages: 176 DOI: 10.3389/978-2-88919-877-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Emergent neural computation from the interaction of different forms of plasticity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197880 Year: Pages: 193 DOI: 10.3389/978-2-88919-788-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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From the propagation of neural activity through synapses, to the integration of signals in the dendritic arbor, and the processes determining action potential generation, virtually all aspects of neural processing are plastic. This plasticity underlies the remarkable versatility and robustness of cortical circuits: it enables the brain to learn regularities in its sensory inputs, to remember the past, and to recover function after injury. While much of the research into learning and memory has focused on forms of Hebbian plasticity at excitatory synapses (LTD/LTP, STDP), several other plasticity mechanisms have been characterized experimentally, including the plasticity of inhibitory circuits (Kullmann, 2012), synaptic scaling (Turrigiano, 2011) and intrinsic plasticity (Zhang and Linden, 2003). However, our current understanding of the computational roles of these plasticity mechanisms remains rudimentary at best. While traditionally they are assumed to serve a homeostatic purpose, counterbalancing the destabilizing effects of Hebbian learning, recent work suggests that they can have a profound impact on circuit function (Savin 2010, Vogels 2011, Keck 2012). Hence, theoretical investigation into the functional implications of these mechanisms may shed new light on the computational principles at work in neural circuits. This Research Topic of Frontiers in Computational Neuroscience aims to bring together recent advances in theoretical modeling of different plasticity mechanisms and of their contributions to circuit function. Topics of interest include the computational roles of plasticity of inhibitory circuitry, metaplasticity, synaptic scaling, intrinsic plasticity, plasticity within the dendritic arbor and in particular studies on the interplay between homeostatic and Hebbian plasticity, and their joint contribution to network function.

Neural and Synaptic Defects in Autism Spectrum Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196289 Year: Pages: 285 DOI: 10.3389/978-2-88919-628-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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Autism spectrum disorders (ASDs) are a group of genetically and clinically heterogeneous neurodevelopmental disorders characterized by impaired reciprocal social interactions and communication, and restricted and repetitive patterns of behaviors and interests. Studies in genetics, neurobiology and systems biology are providing insights into the pathogenesis of ASDs. Investigation of neural and synaptic defects in ASDs not only sheds light on the molecular and cellular mechanisms that govern the function of the central nervous system, but may lead to the discovery of potential therapeutic targets for autism and other cognitive disorders. Our Research Topic which constitutes this e-book documents the recent development and ideas in the study of pathogenesis and treatment of ASDs, with an emphasis on syndromic disorders such as fragile X and Rett syndromes. In addition, model systems and methodological approaches with translational relevance to autism are covered herein. We hope that the Research Topic will enhance the global knowledge base in the autism research community and foster new research directions in autism related biology.

Diacylglycerol Kinase Signalling

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453351 Year: Pages: 96 DOI: 10.3389/978-2-88945-335-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2018-02-27 16:16:45
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Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs. These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems.In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses. In plants DGK mediated PA formation contributes to plant responses to environmental signals.Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential.

Neural Computation in Embodied Closed-Loop Systems for the Generation of Complex Behavior: From Biology to Technology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456055 Year: Pages: 278 DOI: 10.3389/978-2-88945-605-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:43
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How can neural and morphological computations be effectively combined and realized in embodied closed-loop systems (e.g., robots) such that they can become more like living creatures in their level of performance? Understanding this will lead to new technologies and a variety of applications.To tackle this research question, here, we bring together experts from different fields (including Biology, Computational Neuroscience, Robotics, and Artificial Intelligence) to share their recent findings and ideas and to update our research community. This eBook collects 17 cutting edge research articles, covering neural and morphological computations as well as the transfer of results to real world applications, like prosthesis and orthosis control and neuromorphic hardware implementation.

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