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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.

What can neuroscience learn from contemplative practices?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199716 Year: Pages: 166 DOI: 10.3389/978-2-88919-971-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Psychology
Added to DOAB on : 2016-01-19 14:05:46
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A recent wave of brain research has advanced our understanding of the neural mechanisms of conscious states, contents and functions. A host of questions remain to be explored, as shown by lively debates between models of higher vs. lower-order aspects of consciousness, as well as global vs. local models. (Baars 2007; Block, 2009; Dennett and Cohen, 2011; Lau and Rosenthal, 2011). Over some twenty-five centuries the contemplative traditions have also developed explicit descriptions and taxonomies of the mind, to interpret experiences that are often reported in contemplative practices (Radhakrishnan & Moore, 1967; Rinbochay & Naper, 1981). These traditional descriptions sometimes converge on current scientific debates, such as the question of conceptual vs. non-conceptual consciousness; reflexivity or “self-knowing” associated with consciousness; the sense of self and consciousness; and aspects of consciousness that are said to continue during sleep. These real or claimed aspects of consciousness have not been fully integrated into scientific models so far. This Research Topic in Consciousness Research aims to provide a forum for theoretical proposals, new empirical findings, integrative literature reviews, and methodological improvements inspired by meditation-based models. We include a broad array of topics, including but not limited to: replicable findings from a variety of systematic mental practices; changes in brain functioning and organization that can be attributed to such practices; their effects on adaptation and neural plasticity; measurable effects on perception, cognition, affect and self-referential processes. We include contributions that address the question of causal attribution. Many published studies are correlational in nature, because of the inherent difficulty of conducting longitudinal experiments based on a major lifestyle decision, such as the decision to commit to a mental practice over a period of years. We also feature clinical and case studies, integrative syntheses and significant opinion articles.

Anatomy and Plasticity in Large-Scale Brain Models

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450657 Year: Pages: 173 DOI: 10.3389/978-2-88945-065-7 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Supercomputing facilities are becoming increasingly available for simulating activity dynamics in large-scale neuronal networks. On today's most advanced supercomputers, networks with up to a billion of neurons can be readily simulated. However, building biologically realistic, full-scale brain models requires more than just a huge number of neurons. In addition to network size, the detailed local and global anatomy of neuronal connections is of crucial importance. Moreover, anatomical connectivity is not fixed, but can rewire throughout life (structural plasticity)—an aspect that is missing in most current network models, in which plasticity is confined to changes in synaptic strength (synaptic plasticity). The papers in this Ebook, which may broadly be divided into three themes, aim to bring together high-performance computing with recent experimental and computational research in neuroanatomy. In the first theme (fiber connectivity), new methods are described for measuring and data-basing microscopic and macroscopic connectivity. In the second theme (structural plasticity), novel models are introduced that incorporate morphological plasticity and rewiring of anatomical connections. In the third theme (large-scale simulations), simulations of large-scale neuronal networks are presented with an emphasis on anatomical detail and plasticity mechanisms. Together, the articles in this Ebook make the reader aware of the methods and models by which large-scale brain networks running on supercomputers can be extended to include anatomical detail and plasticity.Supercomputing facilities are becoming increasingly available for simulating activity dynamics in large-scale neuronal networks. On today's most advanced supercomputers, networks with up to a billion of neurons can be readily simulated. However, building biologically realistic, full-scale brain models requires more than just a huge number of neurons. In addition to network size, the detailed local and global anatomy of neuronal connections is of crucial importance. Moreover, anatomical connectivity is not fixed, but can rewire throughout life (structural plasticity)—an aspect that is missing in most current network models, in which plasticity is confined to changes in synaptic strength (synaptic plasticity). The papers in this Ebook, which may broadly be divided into three themes, aim to bring together high-performance computing with recent experimental and computational research in neuroanatomy. In the first theme (fiber connectivity), new methods are described for measuring and data-basing microscopic and macroscopic connectivity. In the second theme (structural plasticity), novel models are introduced that incorporate morphological plasticity and rewiring of anatomical connections. In the third theme (large-scale simulations), simulations of large-scale neuronal networks are presented with an emphasis on anatomical detail and plasticity mechanisms. Together, the articles in this Ebook make the reader aware of the methods and models by which large-scale brain networks running on supercomputers can be extended to include anatomical detail and plasticity.

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.

Adult neurogenesis twenty years later: physiological function versus brain repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194940 Year: Pages: 120 DOI: 10.3389/978-2-88919-494-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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The discovery that mammalian brains contain neural stem cells which perform adult neurogenesis - the production and integration of new neurons into mature neural circuits - has provided a fully new vision of neural plasticity. On a theoretical basis, this achievement opened new perspectives for therapeutic approaches in restorative and regenerative neurology. Nevertheless, in spite of striking advancement concerning the molecular and cellular mechanisms which allow and regulate the neurogenic process, its exploitation in mammals for brain repair strategies remains unsolved. In non-mammalian vertebrates, adult neurogenesis also contributes to brain repair/regeneration. In mammals, neural stem cells do respond to pathological conditions in the so called "reactive neurogenesis", yet without substantial regenerative outcome. Why, even in the presence of stem cells in the brain, we lack an effective reparative outcome in terms of regenerative neurology, and which factors hamper the attainment of this goal? Essentially, what remains unanswered is the question whether (and how) physiological functions of adult neurogenesis in mammals can be exploited for brain repair purposes.

Plasticity of GABAergic synapses

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197323 Year: Pages: 175 DOI: 10.3389/978-2-88919-732-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was hypothesized to mainly rely on the flexibility of glutamatergic excitatory synapses, whereas inhibitory synapses were assumed relatively invariant, to ensure stable and reliable control of the neuronal network. As a consequence, while considerable efforts were made to clarify the main mechanisms underlying plasticity at excitatory synapses, the study of the cellular/molecular mechanisms of inhibitory plasticity has received much less attention. Nevertheless, an increasing body of evidence has revealed that inhibitory synapses undergo several types of plasticity at both pre- and postsynaptic levels. Given the crucial role of inhibitory interneurons in shaping network activities, such as generation of oscillations, selection of cell assemblies and signal integration, modifications of the inhibitory synaptic strength represents an extraordinary source of versatility for the fine control of brain states. This versatility also results from the rich diversity of GABAergic neurons in several brain areas, the specific role played by each inhibitory neuron subtype within a given circuit, and the heterogeneity of the properties and modulation of GABAergic synapses formed by specific interneuron classes. The molecular mechanisms underlying the potentiation or depression of inhibitory synapses are now beginning to be unraveled. At the presynaptic level, retrograde synaptic signaling was demonstrated to modulate GABA release, whereas postsynaptic forms of plasticity involve changes in the number/gating properties of GABAA receptors and/or shifts of chloride gradients. In addition, recent research indicates that GABAergic tonic inhibition can also be plastic, adding a further level of complexity to the control of the excitatory/inhibitory balance in the brain. The present Topic will focus on plasticity of GABAergic synapses, with special emphasis on the molecular mechanisms of plasticity induction and/or expression.

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