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      Optogenetics: 10 years after ChR2 in neurons--views from the community.

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          Dimensionality reduction for large-scale neural recordings.

          Most sensory, cognitive and motor functions depend on the interactions of many neurons. In recent years, there has been rapid development and increasing use of technologies for recording from large numbers of neurons, either sequentially or simultaneously. A key question is what scientific insight can be gained by studying a population of recorded neurons beyond studying each neuron individually. Here, we examine three important motivations for population studies: single-trial hypotheses requiring statistical power, hypotheses of population response structure and exploratory analyses of large data sets. Many recent studies have adopted dimensionality reduction to analyze these populations and to find features that are not apparent at the level of individual neurons. We describe the dimensionality reduction methods commonly applied to population activity and offer practical advice about selecting methods and interpreting their outputs. This review is intended for experimental and computational researchers who seek to understand the role dimensionality reduction has had and can have in systems neuroscience, and who seek to apply these methods to their own data.
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            Neural substrates of awakening probed with optogenetic control of hypocretin neurons.

            The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.
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              Channelrhodopsin-1: a light-gated proton channel in green algae.

              Phototaxis and photophobic responses of green algae are mediated by rhodopsins with microbial-type chromophores. We report a complementary DNA sequence in the green alga Chlamydomonas reinhardtii that encodes a microbial opsin-related protein, which we term Channelopsin-1. The hydrophobic core region of the protein shows homology to the light-activated proton pump bacteriorhodopsin. Expression of Channelopsin-1, or only the hydrophobic core, in Xenopus laevis oocytes in the presence of all-trans retinal produces a light-gated conductance that shows characteristics of a channel selectively permeable for protons. We suggest that Channelrhodopsins are involved in phototaxis of green algae.
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                Author and article information

                Journal
                Nat. Neurosci.
                Nature neuroscience
                1546-1726
                1097-6256
                Sep 2015
                : 18
                : 9
                Affiliations
                [1 ] Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, Canada, and the Department of Neurology, Inselspital University Hospital, University of Bern, Bern, Switzerland.
                [2 ] Biozentrum, Department of Cell Biology, University of Basel, Basel, Switzerland, and the Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
                [3 ] Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
                [4 ] Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
                [5 ] Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, Maryland, USA, the Solomon H. Snyder Neuroscience Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, and in the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
                [6 ] The Neuroscience Institute, School of Medicine and Center for Neural Science, New York University, New York, New York, USA.
                [7 ] Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA, and at the Kavli Institute of Neuroscience, Yale University, New Haven, Connecticut, USA.
                [8 ] Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal.
                [9 ] Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.
                [10 ] RIKEN Brain Science Institute, Wako-shi, Saitama, Japan.
                [11 ] McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
                [12 ] Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
                [13 ] Institut für Biologie/Experimentelle Biophysik, Humboldt Universität zu Berlin, Berlin, Germany.
                [14 ] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
                [15 ] National Institute of Mental Health, Bethesda, Maryland, USA.
                [16 ] Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland, USA, and the Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA.
                [17 ] Department of Neuroscience and Center for Learning and Memory, University of Texas at Austin, Austin, Texas, USA.
                [18 ] Program in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada, and the Departments of Psychology and Physiology and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
                [19 ] Allen Institute for Brain Science, Seattle, Washington, USA.
                [20 ] The Gladstone Institutes, San Francisco, California, USA, and the Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, California, USA.
                [21 ] Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland, and the Service of Neurology, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland.
                [22 ] Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, California, USA.
                [23 ] Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, UK.
                [24 ] Institute for Molecular Plant Physiology and Biophysics, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, Germany.
                [25 ] Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Department of Ophthalmology, University of Basel, Basel, Switzerland.
                [26 ] James H. Clark Center for Biomedical Engineering and Sciences, Stanford University, Stanford, California, USA, the Howard Hughes Medical Institute, Stanford University, Stanford, California, USA, and the CNC Program, Stanford University, Stanford, California, USA.
                [27 ] Departments of Electrical Engineering, Bioengineering and Neurobiology, the Neurosciences and Bio-X Programs, the Stanford Neurosciences Institute and the Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
                [28 ] Department of Neurosurgery, Stanford University, Stanford, California, USA.
                [29 ] Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
                [30 ] Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Medical Center, New York, New York, USA.
                [31 ] Department of Pharmacology, Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
                [32 ] Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts, USA.
                [33 ] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
                [34 ] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
                Article
                nn.4106
                10.1038/nn.4106
                26308981
                f1ec11d3-5fbf-45dd-ad35-5e9268bc0d7c
                History

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