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      The impact of tonic GABA A receptor-mediated inhibition on neuronal excitability varies across brain region and cell type

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          The diversity of GABA A receptor (GABA AR) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance. The specific functions of tonic versus phasic GABAergic inhibition in different cell types and the impact on specific neural circuits are only beginning to be unraveled. Here we review the diversity in the magnitude of tonic GABAergic inhibition in various brain regions and cell types, and highlight the impact on neuronal excitability in different neuronal circuits. Further, we discuss the relevance of tonic inhibition in various physiological and pathological contexts as well as the potential of targeting these receptor subtypes for treatment of diseases, such as epilepsy.

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          Most cited references 198

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          Interneurons of the hippocampus.

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            Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks.

            Gamma frequency oscillations are thought to provide a temporal structure for information processing in the brain. They contribute to cognitive functions, such as memory formation and sensory processing, and are disturbed in some psychiatric disorders. Fast-spiking, parvalbumin-expressing, soma-inhibiting interneurons have a key role in the generation of these oscillations. Experimental analysis in the hippocampus and the neocortex reveals that synapses among these interneurons are highly specialized. Computational analysis further suggests that synaptic specialization turns interneuron networks into robust gamma frequency oscillators.
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              Storage of 7 +/- 2 short-term memories in oscillatory subcycles.

               M Idiart,  J Lisman (1995)
              Psychophysical measurements indicate that human subjects can store approximately seven short-term memories. Physiological studies suggest that short-term memories are stored by patterns of neuronal activity. Here it is shown that activity patterns associated with multiple memories can be stored in a single neural network that exhibits nested oscillations similar to those recorded from the brain. Each memory is stored in a different high-frequency ("40 hertz") subcycle of a low-frequency oscillation. Memory patterns repeat on each low-frequency (5 to 12 hertz) oscillation, a repetition that relies on activity-dependent changes in membrane excitability rather than reverberatory circuits. This work suggests that brain oscillations are a timing mechanism for controlling the serial processing of short-term memories.

                Author and article information

                Front Neural Circuits
                Front Neural Circuits
                Front. Neural Circuits
                Frontiers in Neural Circuits
                Frontiers Media S.A.
                03 February 2014
                : 8
                1Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University Boston, MA, USA
                2Department of Neuroscience, Tufts University School of Medicine Boston, MA, USA
                Author notes

                Edited by: Istvan Mody, University of California, Los Angeles, USA

                Reviewed by: Deborah Baro, Georgia State University, USA; Edward S. Ruthazer, McGill University, Canada

                *Correspondence: Jamie Maguire, Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave., SC205, Boston, 02111 MA, USA e-mail: jamie.maguire@ 123456tufts.edu

                This article was submitted to the journal Frontiers in Neural Circuits.

                Copyright © 2014 Lee and Maguire.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 229, Pages: 27, Words: 22029
                Review Article


                neurosteroids, tonic inhibition, gaba, epilepsy, neuronal excitability


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