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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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Abstract

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.

Mechanisms underlying firing in healthy and sick human motoneurons

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195923 Year: Pages: 134 DOI: 10.3389/978-2-88919-592-3 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 the latter half of the twentieth century an enormous amount of knowledge about mammalian motoneuron pools has been collected. This progress was enabled mostly by the development of the precise techniques of intracellular recordings in acute animal experiments, many of which were conducted under deep anaesthesia. Recently obtained evidence indicates that anaesthetics used at that times changed certain properties of the cell membrane, which might affect firing of the neuron. Experiments on normal humans gets around this problem, which lets one compare MN firing characteristics in humans and reduced preparations. Firing pattern of human motoneurons is obtained indirectly by recording from a few muscle fibres of a motor unit. Since there is one-to-one relationship between motor unit and motoneuron firing, the statistical analysis of motor unit firing is equivalent to the analysis of motoneuron firing. This analysis, based on the essential knowledge about motoneuron physiology, gained from the direct measurements in animal experiments and verified by computer simulations, allows one to draw conclusions about the physiological properties of human motoneurons. For obvious reasons, the deductions made on properties of human motoneuron from these analyses should be accepted with caution. On the other hand, human experiments provide the unique opportunity to study intact motoneurons during normal physiological behavior. Thus, combining information obtained from animal and human experiments, and computer simulations, gives insight into underexplored problems of motor control. This E-book contains a collection of articles with range of exciting findings on the physiology and pathology of human motoneurons. The collection covers such important issues concerning firing of healthy motoneurons as recruitment and rate coding as well as motoneuron excitability, discusses intrinsic motoneuron properties disclosed by studying double discharges, and provides information on broad spectrum of motoneuron pathology. It is our hope that this collection promotes further expansion of knowledge on human motoneurons.

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