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      Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms

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          Abstract

          Electrical coupling in circuits can produce non‐intuitive circuit dynamics, as seen in both experimental work from the crustacean stomatogastric ganglion and in computational models inspired by the connectivity in this preparation. Ambiguities in interpreting the results of electrophysiological recordings can arise if sets of pre‐ or postsynaptic neurons are electrically coupled, or if the electrical coupling exhibits some specificity (e.g. rectifying, or voltage‐dependent). Even in small circuits, electrical coupling can produce parallel pathways that can allow information to travel by monosynaptic and/or polysynaptic pathways. Consequently, similar changes in circuit dynamics can arise from entirely different underlying mechanisms. When neurons are coupled both chemically and electrically, modifying the relative strengths of the two interactions provides a mechanism for flexibility in circuit outputs. This, together with neuromodulation of gap junctions and coupled neurons is important both in developing and adult circuits. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 597–609, 2017

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          Electrical synapses in the mammalian brain.

          Many neurons in the mammalian central nervous system communicate through electrical synapses, defined here as gap junction-mediated connections. Electrical synapses are reciprocal pathways for ionic current and small organic molecules. They are often strong enough to mediate close synchronization of subthreshold and spiking activity among clusters of neurons. The most thoroughly studied electrical synapses occur between excitatory projection neurons of the inferior olivary nucleus and between inhibitory interneurons of the neocortex, hippocampus, and thalamus. All these synapses require the gap junction protein connexin36 (Cx36) for robust electrical coupling. Cx36 appears to interconnect neurons exclusively, and it is expressed widely along the mammalian neuraxis, implying that there are undiscovered electrical synapses throughout the central nervous system. Some central neurons may be electrically coupled by other connexin types or by pannexins, a newly described family of gap junction proteins. Electrical synapses are a ubiquitous yet underappreciated feature of neural circuits in the mammalian brain.
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            Transmission at the giant motor synapses of the crayfish.

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              High-resolution whole-brain staining for electron microscopic circuit reconstruction.

              Currently only electron microscopy provides the resolution necessary to reconstruct neuronal circuits completely and with single-synapse resolution. Because almost all behaviors rely on neural computations widely distributed throughout the brain, a reconstruction of brain-wide circuits-and, ultimately, the entire brain-is highly desirable. However, these reconstructions require the undivided brain to be prepared for electron microscopic observation. Here we describe a preparation, BROPA (brain-wide reduced-osmium staining with pyrogallol-mediated amplification), that results in the preservation and staining of ultrastructural details throughout the brain at a resolution necessary for tracing neuronal processes and identifying synaptic contacts between them. Using serial block-face electron microscopy (SBEM), we tested human annotator ability to follow neural 'wires' reliably and over long distances as well as the ability to detect synaptic contacts. Our results suggest that the BROPA method can produce a preparation suitable for the reconstruction of neural circuits spanning an entire mouse brain.
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                Author and article information

                Contributors
                ellag9@uw.edu
                Journal
                Dev Neurobiol
                Dev Neurobiol
                10.1002/(ISSN)1932-846X
                DNEU
                Developmental Neurobiology
                John Wiley and Sons Inc. (Hoboken )
                1932-8451
                1932-846X
                08 August 2016
                May 2017
                : 77
                : 5 , Electrical Synapses: Development, Function and Plasticity ( doiID: 10.1002/dneu.v77.5 )
                : 597-609
                Affiliations
                [ 1 ] Volen Center and Biology DepartmentBrandeis University Waltham MA
                [ 2 ] Department of Applied MathematicsUniversity of Washington Seattle WA
                [ 3 ] Department of Neuroscience, Perelman School of MedicineUniversity of Pennsylvania Philadelphia PA
                Author notes
                [*] [* ] Correspondence to: G. J. Gutierrez ( ellag9@ 123456uw.edu )
                Article
                DNEU22410
                10.1002/dneu.22410
                5412840
                27314561
                54674f2d-161f-49ad-b7ec-fcbcbfb32eab
                © 2016 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 April 2016
                : 14 June 2016
                : 14 June 2016
                Page count
                Figures: 9, Tables: 0, Pages: 13, Words: 6981
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                dneu22410
                May 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:02.05.2017

                Neurosciences
                gap junctions,neuronal networks,stomatogastric,ganglion,inhibition,oscillations
                Neurosciences
                gap junctions, neuronal networks, stomatogastric, ganglion, inhibition, oscillations

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