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      Midbrain circuits that set locomotor speed and gait selection

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          Summary

          Locomotion is a fundamental motor function common to the animal kingdom. It is executed episodically and adapted to behavioural needs including exploration, requiring slow locomotion, and escaping behaviour, necessitating faster speeds. The control of these functions originates in brainstem structures although the neuronal substrate(s) supporting them are debated. Here, we show in mice that speed/gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the Cuneiform Nucleus (CnF) and the Pedunculopontine Nucleus (PPN). GlutNs in each of those two regions are sufficient for controlling slower alternating locomotor behavior but only GlutNs in the CnF are necessary for high-speed synchronous locomotion. Additionally, PPN- and CnF-GlutNs activation dynamics and their input and output connectivity matrices support explorative and escape locomotion, respectively. Our results identify dual regions in the midbrain that act in common to select context dependent locomotor behaviours.

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          Most cited references40

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          Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering.

          This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wavelet transform, which localizes distinctive spike features, with superparamagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods.
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            DREADDs for Neuroscientists.

            Bryan Roth (2016)
            To understand brain function, it is essential that we discover how cellular signaling specifies normal and pathological brain function. In this regard, chemogenetic technologies represent valuable platforms for manipulating neuronal and non-neuronal signal transduction in a cell-type-specific fashion in freely moving animals. Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are now commonly used by neuroscientists to identify the circuitry and cellular signals that specify behavior, perceptions, emotions, innate drives, and motor functions in species ranging from flies to nonhuman primates. Here I provide a primer on DREADDs highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.
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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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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                11 December 2017
                17 January 2018
                25 January 2018
                17 July 2018
                : 553
                : 7689
                : 455-460
                Affiliations
                [1 ]Mammalian Locomotor Laboratory, Karolinska Institutet 17177 Stockholm, Sweden
                [2 ]Laboratory of Molecular Neuropharmacology, Department of Neuroscience, Karolinska Institutet 17177 Stockholm, Sweden
                [3 ]Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
                Author notes
                [# ]Correspondences: Lead corresponding author Ole Kiehn: Ole.Kiehn@ 123456ki.se or Ole.Kiehn@ 123456sund.ku.dk . Vittorio Caggiano: Caggiano@ 123456gmail.com . Roberto Leiras: roberto.leiras@ 123456ki.se , Lead contact: Ole Kiehn
                [4]

                Present address: Computational Biology Center, IBM T.J. Watson Research Center, 1101 Kitchawan Road, Route 134, Room 30-048, Yorktown Heights, NY 10598

                [5]

                Present address: Paris-Saclay Institute of Neuroscience, UMR9197, CNRS and Université Paris-11, 91190 Gif-Sur-Yvette, France

                [*]

                These authors contributed equally

                Correspondence and requests for materials should be addressed to Ole.Kiehn@ 123456sund.ku.dk or Ole.Kiehn@ 123456ki.se

                Article
                NIHMS926480
                10.1038/nature25448
                5937258
                29342142
                2aa55d40-1563-4d28-b71a-c2e8517b91c7

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                motor behaviour,brainstem,mesencephalic locomotor region,basal ganglia,glutamatergic neurons

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