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  • 1
    Publication Date: 2015-07-29
    Description: Entorhinal–hippocampal circuits in the mammalian brain are crucial for an animal’s spatial and episodic experience, but the neural basis for different spatial computations remain unknown. Medial entorhinal cortex layer II contains pyramidal island and stellate ocean cells. Here, we performed cell type-specific Ca2+ imaging in freely exploring mice using cellular...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2010-01-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnitzer, Mark J -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jan 21;463(7279):273. doi: 10.1038/463273e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University and Howard Hughes Medical Institute, California, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090712" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Humans ; Learning/*physiology ; Models, Neurological ; Movement/physiology ; Psychomotor Performance/*physiology ; Robotics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2008-07-05
    Description: Sarcomeres are the basic contractile units of striated muscle. Our knowledge about sarcomere dynamics has primarily come from in vitro studies of muscle fibres and analysis of optical diffraction patterns obtained from living muscles. Both approaches involve highly invasive procedures and neither allows examination of individual sarcomeres in live subjects. Here we report direct visualization of individual sarcomeres and their dynamical length variations using minimally invasive optical microendoscopy to observe second-harmonic frequencies of light generated in the muscle fibres of live mice and humans. Using microendoscopes as small as 350 microm in diameter, we imaged individual sarcomeres in both passive and activated muscle. Our measurements permit in vivo characterization of sarcomere length changes that occur with alterations in body posture and visualization of local variations in sarcomere length not apparent in aggregate length determinations. High-speed data acquisition enabled observation of sarcomere contractile dynamics with millisecond-scale resolution. These experiments point the way to in vivo imaging studies demonstrating how sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826360/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826360/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Llewellyn, Michael E -- Barretto, Robert P J -- Delp, Scott L -- Schnitzer, Mark J -- R01 NS050533/NS/NINDS NIH HHS/ -- R01 NS050533-01/NS/NINDS NIH HHS/ -- R01NS050533/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Aug 7;454(7205):784-8. doi: 10.1038/nature07104. Epub 2008 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bio-X Program, James H. Clark Center for Biomedical Engineering & Sciences, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18600262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Survival ; Endoscopy/*methods ; Humans ; Mice ; Mice, Inbred C57BL ; Movement/*physiology ; Muscle Contraction/*physiology ; Optics and Photonics ; Sarcomeres/*metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1998-10-30
    Description: RNA polymerase (RNAP) moves along DNA while carrying out transcription, acting as a molecular motor. Transcriptional velocities for single molecules of Escherichia coli RNAP were measured as progressively larger forces were applied by a feedback-controlled optical trap. The shapes of RNAP force-velocity curves are distinct from those of the motor enzymes myosin or kinesin, and indicate that biochemical steps limiting transcription rates at low loads do not generate movement. Modeling the data suggests that high loads may halt RNAP by promoting a structural change which moves all or part of the enzyme backwards through a comparatively large distance, corresponding to 5 to 10 base pairs. This contrasts with previous models that assumed force acts directly upon a single-base translocation step.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, M D -- Schnitzer, M J -- Yin, H -- Landick, R -- Gelles, J -- Block, S M -- New York, N.Y. -- Science. 1998 Oct 30;282(5390):902-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Princeton Materials Institute, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9794753" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Bacterial/metabolism ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Escherichia coli/enzymology ; Mathematics ; *Models, Chemical ; Molecular Motor Proteins/*chemistry/metabolism ; RNA, Bacterial/biosynthesis ; RNA, Messenger/biosynthesis ; Templates, Genetic ; Thermodynamics ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-06-23
    Description: The mammalian hippocampus is crucial for episodic memory formation and transiently retains information for about 3-4 weeks in adult mice and longer in humans. Although neuroscientists widely believe that neural synapses are elemental sites of information storage, there has been no direct evidence that hippocampal synapses persist for time intervals commensurate with the duration of hippocampal-dependent memory. Here we tested the prediction that the lifetimes of hippocampal synapses match the longevity of hippocampal memory. By using time-lapse two-photon microendoscopy in the CA1 hippocampal area of live mice, we monitored the turnover dynamics of the pyramidal neurons' basal dendritic spines, postsynaptic structures whose turnover dynamics are thought to reflect those of excitatory synaptic connections. Strikingly, CA1 spine turnover dynamics differed sharply from those seen previously in the neocortex. Mathematical modelling revealed that the data best matched kinetic models with a single population of spines with a mean lifetime of approximately 1-2 weeks. This implies approximately 100% turnover in approximately 2-3 times this interval, a near full erasure of the synaptic connectivity pattern. Although N-methyl-d-aspartate (NMDA) receptor blockade stabilizes spines in the neocortex, in CA1 it transiently increased the rate of spine loss and thus lowered spine density. These results reveal that adult neocortical and hippocampal pyramidal neurons have divergent patterns of spine regulation and quantitatively support the idea that the transience of hippocampal-dependent memory directly reflects the turnover dynamics of hippocampal synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648621/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Attardo, Alessio -- Fitzgerald, James E -- Schnitzer, Mark J -- R21 AG038771/AG/NIA NIH HHS/ -- R21 MH092809/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Jul 30;523(7562):592-6. doi: 10.1038/nature14467. Epub 2015 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA [2] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. ; James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA. ; 1] James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA [2] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA [3] CNC Program, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26098371" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CA1 Region, Hippocampal/*cytology/*metabolism ; Dendritic Spines/*metabolism ; Endoscopy ; Kinetics ; Male ; Memory, Episodic ; Mice ; Neocortex/cytology/metabolism ; Neuronal Plasticity/*physiology ; Photons ; Pyramidal Cells/cytology/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-11-11
    Description: The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297533/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297533/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barretto, Robert P J -- Gillis-Smith, Sarah -- Chandrashekar, Jayaram -- Yarmolinsky, David A -- Schnitzer, Mark J -- Ryba, Nicholas J P -- Zuker, Charles S -- ZIA DE000561-22/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 15;517(7534):373-6. doi: 10.1038/nature13873. Epub 2014 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Departments of Biochemistry and Molecular Biophysics and of Neuroscience, Columbia College of Physicians and Surgeons, Columbia University, New York 10032, USA. ; Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA. ; James H. Clark Center, Stanford University, Stanford, California 94305, USA. ; National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Howard Hughes Medical Institute and Departments of Biochemistry and Molecular Biophysics and of Neuroscience, Columbia College of Physicians and Surgeons, Columbia University, New York 10032, USA [2] Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Geniculate Ganglion/*cytology ; Mice ; Mice, Transgenic ; Neurons/*physiology ; Taste/*physiology ; Taste Buds/cytology/physiology ; Taste Perception/*physiology ; Tongue/cytology/innervation/*physiology
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    Electronic ISSN: 1476-4687
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  • 7
    Publication Date: 2015-11-21
    Description: Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Previous GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores through resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than previous GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Yiyang -- Huang, Cheng -- Li, Jin Zhong -- Grewe, Benjamin F -- Zhang, Yanping -- Eismann, Stephan -- Schnitzer, Mark J -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 11;350(6266):1361-6. doi: 10.1126/science.aab0810. Epub 2015 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. yiyang.gong@duke.edu mschnitz@stanford.edu. ; James H. Clark Center, Stanford University, Stanford, CA 94305, USA. ; James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. ; James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. ; James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. yiyang.gong@duke.edu mschnitz@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586188" target="_blank"〉PubMed〈/a〉
    Keywords: *Action Potentials ; Animals ; *Bioluminescence Resonance Energy Transfer Techniques ; *Biosensing Techniques ; Dendrites/physiology ; Drosophila melanogaster/physiology ; *Evoked Potentials, Somatosensory ; *Fluorescence Resonance Energy Transfer ; Green Fluorescent Proteins/chemistry/genetics ; Mice ; Neurons/*physiology ; Recombinant Fusion Proteins/chemistry/genetics ; Rhodopsin/chemistry/genetics ; Smell
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2011-07-18
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2013-10-28
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    Electronic ISSN: 1091-6490
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  • 10
    Publication Date: 2011-08-03
    Description: The estimation of visual motion has long been studied as a paradigmatic neural computation, and multiple models have been advanced to explain behavioral and neural responses to motion signals. A broad class of models, originating with the Reichardt correlator model, proposes that animals estimate motion by computing a temporal cross-correlation of light intensities from two neighboring points in visual space. These models provide a good description of experimental data in specific contexts but cannot explain motion percepts in stimuli lacking pairwise correlations. Here, we develop a theoretical formalism that can accommodate diverse stimuli and behavioral goals. To achieve this, we treat motion estimation as a problem of Bayesian inference. Pairwise models emerge as one component of the generalized strategy for motion estimation. However, correlation functions beyond second order enable more accurate motion estimation. Prior expectations that are asymmetric with respect to bright and dark contrast use correlations of both even and odd orders, and we show that psychophysical experiments using visual stimuli with symmetric probability distributions for contrast cannot reveal whether the subject uses odd-order correlators for motion estimation. This result highlights a gap in previous experiments, which have largely relied on symmetric contrast distributions. Our theoretical treatment provides a natural interpretation of many visual motion percepts, indicates that motion estimation should be revisited using a broader class of stimuli, demonstrates how correlation-based motion estimation is related to stimulus statistics, and provides multiple experimentally testable predictions.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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