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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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Abstract

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

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.

New Perspectives in Neurosteroids action: a Special Player Allopregnanolone

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195558 Year: Pages: 86 DOI: 10.3389/978-2-88919-555-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.

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