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Brain Cholinergic Mechanisms

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197149 Year: Pages: 127 DOI: 10.3389/978-2-88919-714-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Much of our understanding of brain physiology has focused on what one might call, first order processes. These essentially include the primary synaptic mechanisms underlying excitation (mainly glutamate) and inhibition (mainly GABA). Our attention has focused on how the balance of excitation and inhibition regulates the timing, patterns, and extent of information flow across various circuits. A lot less is understood regarding second order processes that sculpt and modify these primary interactions. One such modulatory transmitter in the brain is acetylcholine (ACh). The importance of ACh in modulating various behaviors related to learning, memory, and attention has been recognized over the last four decades as has its involvement in various neurodegenerative and psychiatric disorders. However, our understanding of the mechanistic bases for these actions is at its infancy, at best and much remains to be understood. The array of receptor subtypes for nicotinic and muscarinic receptors, their different locations, and complex signal transduction mechanisms remain a puzzle. Transmitter (ACh) release sites and their relationship to receptor loci are poorly understood. Overall, we lack a unifying framework for conceptualizing how disparate actions of the transmitter on receptors lead to circuit modulation and, eventually, influences on cognition. By its very nature, reports on cholinergic signaling are quite scattered, presented in journals across sub-disciplines and in the context of the systems they modulate. Hence, there is need for consolidation of these studies under a single cover that would allow one to compare and contrast the effects of this transmitter across systems and contexts. This special issue represents one such compilation. The issue addresses cholinergic modulation of defined circuits that lead to specific behaviors and consists of a judicious mixture of review articles and primary papers. The articles focus on three aspects of the system: 1) Cellular targets of cholinergic signaling. 2) Receptor mechanisms. 3) Endogenous transmitter distribution and action. While no common mechanism emerges that can explain cholinergic actions on brain functions, on can postulate that the transmitter system is dynamic, modulating the balance of excitation and inhibition in various circuits. This modulation sets up timed network oscillations and it is tempting to speculate that these oscillations form a template for better encoding of afferent inputs. One can broadly envision the role of the cholinergic system as facilitating processes that allow for more efficient acquisition of learning and engraving of memories. Thus, understanding the mechanisms underlying tonic and stimulus-dependent release of ACh and how it alters firing templates of neuronal networks would be the first step towards elucidating its role in learning and memory. This special topics edition provides clues to some of the actions of ACh. It is hoped that the articles allow the reader to extract common themes and potential mechanisms of cholinergic regulation that will lead to elucidation of general principles governing the actions of this important neuromodulator.

At The Top of the Interneuronal Pyramid - Calretinin Expressing Cortical Interneurons

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197088 Year: Pages: 102 DOI: 10.3389/978-2-88919-708-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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It is in general well appreciated that the cortical interneurons play various important roles in cortical neuronal networks both in normal and pathological states. Based on connectivity pattern, developmental, morphological and electrophysiological properties, distinct subgroups of GABAergic interneurons can be differentiated in the neocortex as well as in the hippocampal formation. In this E-Book, we are focusing our attention on inhibitory interneurons expressing calcium-binding protein calretinin (CR). The aim of the E-Book is to consolidate the knowledge about this interneuronal population and to inspire further research on the function and malfunction of these neurons, which – functionally – seem to stand "at the top of the pyramid" of cortical interneuronal types.

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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