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  • 1
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    High-performance genetically targetable optical neural silencing by light-driven proton pumps (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-08
    Description: The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939492/" 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/PMC2939492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, Brian Y -- Han, Xue -- Dobry, Allison S -- Qian, Xiaofeng -- Chuong, Amy S -- Li, Mingjie -- Henninger, Michael A -- Belfort, Gabriel M -- Lin, Yingxi -- Monahan, Patrick E -- Boyden, Edward S -- 1K99MH085944/MH/NIMH NIH HHS/ -- DP2 OD002002/OD/NIH HHS/ -- DP2 OD002002-01/OD/NIH HHS/ -- K99 MH085944/MH/NIMH NIH HHS/ -- K99 MH085944-01/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):98-102. doi: 10.1038/nature08652.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054397" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/radiation effects ; Animals ; Ascomycota/metabolism/radiation effects ; Color ; Electric Conductivity ; Euryarchaeota/metabolism/radiation effects ; Genetic Engineering/*methods ; Hydrogen-Ion Concentration ; Mice ; Molecular Sequence Data ; Neocortex/cytology/physiology/radiation effects ; Neurons/*metabolism/*radiation effects ; Proton Pumps/classification/genetics/*metabolism/*radiation effects ; Rhodopsins, Microbial/antagonists & inhibitors/genetics/metabolism/radiation ; effects ; Wakefulness
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Physiology. Synthetic physiology (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-06-28
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553595/" 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/PMC3553595/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, Brian Y -- Boyden, Edward S -- R01 NS075421/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Jun 24;332(6037):1508-9. doi: 10.1126/science.1208555.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700858" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/analysis ; Gene Expression Regulation ; Genes, Reporter ; Genetic Engineering/*methods ; Glucagon-Like Peptide 1/genetics ; Insulin/blood ; *Light ; Light Signal Transduction ; Mice ; NFATC Transcription Factors/metabolism ; Rod Opsins/*genetics/metabolism ; Synthetic Biology/*methods
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Voltage modulation of NV charge state in NDs [Applied Physical Sciences] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-04-13
    Description: The negatively charged nitrogen vacancy (NV−) center in diamond has attracted strong interest for a wide range of sensing and quantum information processing applications. To this end, recent work has focused on controlling the NV charge state, whose stability strongly depends on its electrostatic environment. Here, we demonstrate that the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Activation of specific interneurons improves V1 feature selectivity and visual perception (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-08-11
    Description: Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (gamma-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIalpha (CAMKIIalpha)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422431/" 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/PMC3422431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Seung-Hee -- Kwan, Alex C -- Zhang, Siyu -- Phoumthipphavong, Victoria -- Flannery, John G -- Masmanidis, Sotiris C -- Taniguchi, Hiroki -- Huang, Z Josh -- Zhang, Feng -- Boyden, Edward S -- Deisseroth, Karl -- Dan, Yang -- PN2 EY018241/EY/NEI NIH HHS/ -- R01 EY018861/EY/NEI NIH HHS/ -- R01 NS067199/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Aug 16;488(7411):379-83. doi: 10.1038/nature11312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878719" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/deficiency/genetics/metabolism ; Discrimination Learning ; Interneurons/*physiology ; Mice ; Models, Neurological ; Neural Inhibition/physiology ; Parvalbumins/metabolism ; Rhodopsin/metabolism ; Rhodopsins, Microbial/metabolism ; Visual Cortex/*cytology/*physiology ; Visual Perception/*physiology ; Wakefulness/physiology ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Drug discovery: a jump-start for electroceuticals (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-04-13
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179459/" 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/PMC4179459/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Famm, Kristoffer -- Litt, Brian -- Tracey, Kevin J -- Boyden, Edward S -- Slaoui, Moncef -- R01 GM057226/GM/NIGMS NIH HHS/ -- R01 NS048598/NS/NINDS NIH HHS/ -- U24 NS063930/NS/NINDS NIH HHS/ -- England -- Nature. 2013 Apr 11;496(7444):159-61. doi: 10.1038/496159a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉GlaxoSmithKline, Brentford TW8 9GS, UK. kristoffer.h.famm@gsk.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579662" target="_blank"〉PubMed〈/a〉
    Keywords: *Action Potentials/physiology ; Animals ; Drug Discovery ; Electric Stimulation Therapy/*methods/*trends ; Humans ; Interdisciplinary Communication ; *Neural Pathways/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    Optical imaging. Expansion microscopy (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-17
    Description: In optical microscopy, fine structural details are resolved by using refraction to magnify images of a specimen. We discovered that by synthesizing a swellable polymer network within a specimen, it can be physically expanded, resulting in physical magnification. By covalently anchoring specific labels located within the specimen directly to the polymer network, labels spaced closer than the optical diffraction limit can be isotropically separated and optically resolved, a process we call expansion microscopy (ExM). Thus, this process can be used to perform scalable superresolution microscopy with diffraction-limited microscopes. We demonstrate ExM with apparent ~70-nanometer lateral resolution in both cultured cells and brain tissue, performing three-color superresolution imaging of ~10(7) cubic micrometers of the mouse hippocampus with a conventional confocal microscope.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312537/" 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/PMC4312537/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Fei -- Tillberg, Paul W -- Boyden, Edward S -- 1DP1NS087724/DP/NCCDPHP CDC HHS/ -- 1R01MH103910-01/MH/NIMH NIH HHS/ -- DP1 NS087724/NS/NINDS NIH HHS/ -- R01 MH103910/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):543-8. doi: 10.1126/science.1260088. Epub 2015 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Engineering, Massachussetts Institute of Technology (MIT), Cambridge, MA, USA. ; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA. ; Department of Biological Engineering, Massachussetts Institute of Technology (MIT), Cambridge, MA, USA. Media Lab, MIT, Cambridge, MA, USA. McGovern Institute, MIT, Cambridge, MA, USA. Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA. Center for Neurobiological Engineering, MIT, Cambridge, MA, USA. esb@media.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25592419" target="_blank"〉PubMed〈/a〉
    Keywords: Acrylamide ; Acrylamides ; Acrylates ; Animals ; Coated Pits, Cell-Membrane/*ultrastructure ; Fluorescent Dyes ; Gels ; HEK293 Cells ; Hippocampus/*ultrastructure ; Humans ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy/*methods ; Microscopy, Confocal/methods ; Microscopy, Fluorescence/methods ; Microtubules/*ultrastructure ; Optical Imaging/*methods ; Polymers ; Tissue Fixation
    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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  • 7
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    Anti-Ca2+ channel antibody attenuates Ca2+ currents and mimics cerebellar ataxia in vivo (2008)
    National Academy of Sciences
    Details
    Publication Date: 2008-02-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Striatal origin of the pathologic beta oscillations in Parkinson's disease (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-06-22
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Programmable RNA binding protein [Cell Biology] (2016)
    National Academy of Sciences
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    Publication Date: 2016-05-12
    Description: The ability to monitor and perturb RNAs in living cells would benefit greatly from a modular protein architecture that targets unmodified RNA sequences in a programmable way. We report that the RNA-binding protein PumHD (Pumilio homology domain), which has been widely used in native and modified form for targeting RNA,...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
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    3D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉Lithographic nanofabrication is often limited to successive fabrication of two-dimensional (2D) layers. We present a strategy for the direct assembly of 3D nanomaterials consisting of metals, semiconductors, and biomolecules arranged in virtually any 3D geometry. We used hydrogels as scaffolds for volumetric deposition of materials at defined points in space. We then optically patterned these scaffolds in three dimensions, attached one or more functional materials, and then shrank and dehydrated them in a controlled way to achieve nanoscale feature sizes in a solid substrate. We demonstrate that our process, Implosion Fabrication (ImpFab), can directly write highly conductive, 3D silver nanostructures within an acrylic scaffold via volumetric silver deposition. Using ImpFab, we achieve resolutions in the tens of nanometers and complex, non–self-supporting 3D geometries of interest for optical metamaterials.〈/p〉
    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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