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  • 1
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    Two-photon laser scanning fluorescence microscopy (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-04-06
    Description: Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denk, W -- Strickler, J H -- Webb, W W -- RR04224/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):73-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Applied and Engineering Physics, Department of Physics, Cornell University, Ithaca, NY 14853.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321027" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chromosomes/ultrastructure ; Fluorescent Dyes ; Kidney/ultrastructure ; *Lasers ; Microscopy, Fluorescence/*methods ; Photochemistry ; *Radiation ; Swine ; Ultraviolet Rays
    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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  • 2
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    Space-time wiring specificity supports direction selectivity in the retina (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-05-09
    Description: How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074887/" 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/PMC4074887/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jinseop S -- Greene, Matthew J -- Zlateski, Aleksandar -- Lee, Kisuk -- Richardson, Mark -- Turaga, Srinivas C -- Purcaro, Michael -- Balkam, Matthew -- Robinson, Amy -- Behabadi, Bardia F -- Campos, Michael -- Denk, Winfried -- Seung, H Sebastian -- EyeWirers -- R01 NS076467/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 15;509(7500):331-6. doi: 10.1038/nature13240. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2]. ; Electrical Engineering and Computer Science Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] 601 N 42nd Street, Seattle, Washington 98103, USA (M.R.); Princeton Neuroscience Institute and Computer Science Deptartment, Princeton, New Jersey 08544, USA (H.S.S.); Gatsby Computational Neuroscience Unit, London WC1N 3AR, UK (S.C.T.). ; Qualcomm Research, 5775 Morehouse Drive, San Diego, California 92121, USA. ; Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805243" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/cytology/physiology/ultrastructure ; Animals ; Artificial Intelligence ; *Brain Mapping ; Crowdsourcing ; Dendrites/metabolism ; Mice ; *Models, Neurological ; Motion ; Neural Pathways/*physiology ; Presynaptic Terminals/metabolism ; Retina/*cytology/*physiology ; Retinal Bipolar Cells/cytology/physiology/ultrastructure ; *Spatio-Temporal Analysis
    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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  • 3
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    Connectomic reconstruction of the inner plexiform layer in the mouse retina (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-08-09
    Description: Comprehensive high-resolution structural maps are central to functional exploration and understanding in biology. For the nervous system, in which high resolution and large spatial extent are both needed, such maps are scarce as they challenge data acquisition and analysis capabilities. Here we present for the mouse inner plexiform layer--the main computational neuropil region in the mammalian retina--the dense reconstruction of 950 neurons and their mutual contacts. This was achieved by applying a combination of crowd-sourced manual annotation and machine-learning-based volume segmentation to serial block-face electron microscopy data. We characterize a new type of retinal bipolar interneuron and show that we can subdivide a known type based on connectivity. Circuit motifs that emerge from our data indicate a functional mechanism for a known cellular response in a ganglion cell that detects localized motion, and predict that another ganglion cell is motion sensitive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmstaedter, Moritz -- Briggman, Kevin L -- Turaga, Srinivas C -- Jain, Viren -- Seung, H Sebastian -- Denk, Winfried -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Aug 8;500(7461):168-74. doi: 10.1038/nature12346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany. mhelmstaedter@neuro.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925239" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/cytology/physiology ; Animals ; Cell Communication ; *Connectome ; Image Processing, Computer-Assisted ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; *Models, Biological ; Neuropil/physiology ; Retina/*cytology/*physiology ; Retinal Ganglion Cells/cytology/*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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  • 4
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    Wiring specificity in the direction-selectivity circuit of the retina (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-03-11
    Description: The proper connectivity between neurons is essential for the implementation of the algorithms used in neural computations, such as the detection of directed motion by the retina. The analysis of neuronal connectivity is possible with electron microscopy, but technological limitations have impeded the acquisition of high-resolution data on a large enough scale. Here we show, using serial block-face electron microscopy and two-photon calcium imaging, that the dendrites of mouse starburst amacrine cells make highly specific synapses with direction-selective ganglion cells depending on the ganglion cell's preferred direction. Our findings indicate that a structural (wiring) asymmetry contributes to the computation of direction selectivity. The nature of this asymmetry supports some models of direction selectivity and rules out others. It also puts constraints on the developmental mechanisms behind the formation of synaptic connections. Our study demonstrates how otherwise intractable neurobiological questions can be addressed by combining functional imaging with the analysis of neuronal connectivity using large-scale electron microscopy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Briggman, Kevin L -- Helmstaedter, Moritz -- Denk, Winfried -- England -- Nature. 2011 Mar 10;471(7337):183-8. doi: 10.1038/nature09818.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Medical Research, Department of Biomedical Optics, Heidelberg 69120, Germany. briggman@mpimf-heidelberg.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21390125" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/cytology/physiology/ultrastructure ; Animals ; Calcium Signaling ; Dendrites/physiology ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; Microscopy, Fluorescence ; Models, Neurological ; Neural Pathways/cytology/*physiology/ultrastructure ; Neuroanatomical Tract-Tracing Techniques ; Retina/anatomy & histology/*cytology/*physiology/ultrastructure ; Retinal Ganglion Cells/cytology/physiology/ultrastructure ; Synapses/physiology/ultrastructure
    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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    Direct measurement of coupling between dendritic spines and shafts (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-05-03
    Description: Characterization of the diffusional and electrotonic coupling of spines to the dendritic shaft is crucial to understanding neuronal integration and synaptic plasticity. Two-photon photobleaching and photorelease of fluorescein dextran were used to generate concentration gradients between spines and shafts in rat CA1 pyramidal neurons. Diffusional reequilibration was monitored with two-photon fluorescence imaging. The time course of reequilibration was exponential, with time constants in the range of 20 to 100 milliseconds, demonstrating chemical compartmentalization on such time scales. These values imply that electrical spine neck resistances are unlikely to exceed 150 megohms and more likely range from 4 to 50 megohms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Svoboda, K -- Tank, D W -- Denk, W -- New York, N.Y. -- Science. 1996 May 3;272(5262):716-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Computation Research Department, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendrites/metabolism/*physiology/ultrastructure ; Dextrans/metabolism ; Diffusion ; Electric Conductivity ; Electric Impedance ; Fluoresceins/metabolism ; Fluorescence ; In Vitro Techniques ; Kinetics ; Microscopy/methods ; Models, Neurological ; Neuronal Plasticity ; Pyramidal Cells/metabolism/*physiology/ultrastructure ; Rats
    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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  • 6
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    The big and the small: challenges of imaging the brain's circuits (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-11-05
    Description: The relation between the structure of the nervous system and its function is more poorly understood than the relation between structure and function in any other organ system. We explore why bridging the structure-function divide is uniquely difficult in the brain. These difficulties also explain the thrust behind the enormous amount of innovation centered on microscopy in neuroscience. We highlight some recent progress and the challenges that remain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lichtman, Jeff W -- Denk, Winfried -- 43667/Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Nov 4;334(6056):618-23. doi: 10.1126/science.1209168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. jeff@mcb.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22053041" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/*physiology ; Brain Chemistry ; Electrophysiology ; Humans ; Microscopy ; *Nerve Net ; *Neural Pathways ; Neuroimaging ; Neurons/cytology/physiology
    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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