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      Spinal Shox2 interneuron interconnectivity related to function and development

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          Abstract

          Neuronal networks generating hindlimb locomotion are located in the spinal cord. The mechanisms underlying spinal rhythmogenesis are unknown but network activity and interconnectivity of excitatory interneurons likely play prominent roles. Here, we investigate interconnectivity within the Shox2 interneuron population, a subset of which has been suggested to be involved in locomotor rhythm generation, using paired recordings in isolated spinal cords or slices from transgenic mice. Sparse unidirectional connections consistent with chemical synaptic transmission and prominent bidirectional connections mediated by electrical synapses were present within distinct subsets of Shox2 interneurons. Moreover, bidirectional electrical connections were preferentially found between functionally-related Shox2 interneurons. Though prevalent in neonatal mice, electrical coupling began to decline in incidence and strength in mice ~ 3 weeks of age. Overall, our data suggest that gap junctional coupling promotes synchronization of Shox2 interneurons, and may be implicated in locomotor rhythmicity in developing mice.

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          Most cited references80

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          A gene expression atlas of the central nervous system based on bacterial artificial chromosomes.

          The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.
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            Decoding the organization of spinal circuits that control locomotion.

            Ole Kiehn (2016)
            Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait.
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              Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice.

              Long-term potentiation (LTP) is an enhancement of synaptic strength that can be produced by pairing of presynaptic activity with postsynaptic depolarization. LTP in the hippocampus has been extensively studied as a cellular model of learning and memory, but the nature of the underlying synaptic modification remains elusive, partly because our knowledge of central synapses is still limited. One proposal is that the modification is postsynaptic, and that synapses expressing only NMDA (N-methyl-D-aspartate) receptors before potentiation are induced by LTP to express functional AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors. Here we report that a high proportion of synapses in hippocampal area CA1 transmit with NMDA receptors but not AMPA receptors, making these synapses effectively non-functional at normal resting potentials. These silent synapses acquire AMPA-type responses following LTP induction. Our findings challenge the view that LTP in CA1 involves a presynaptic modification, and suggest instead a simple postsynaptic mechanism for both induction and expression of LTP.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                31 December 2018
                2018
                : 7
                : e42519
                Affiliations
                [1]deptDepartment of Neurobiology and Anatomy Drexel University College of Medicine PhiladelphiaUnited States
                Emory University United States
                Emory University United States
                Emory University United States
                Author information
                http://orcid.org/0000-0002-0807-574X
                Article
                42519
                10.7554/eLife.42519
                6333440
                30596374
                b6d6754b-a3a9-4898-ad59-fca95f1f28fe
                © 2018, Ha and Dougherty

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 03 October 2018
                : 27 December 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 NS095366
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100008191, Wings for Life;
                Award ID: WFL-US-003/15
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                Spinal Shox2 interneurons are strongly interconnected by gap junctional coupling in a function-specific manner, which provides a mechanism for synchronization of rhythm-generating neurons and may contribute to locomotor rhythmicity.

                Life sciences
                spinal cord,rhythm generation,locomotion,synaptic connectivity,gap junctions,mouse
                Life sciences
                spinal cord, rhythm generation, locomotion, synaptic connectivity, gap junctions, mouse

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