Journal ArticleDOI
Wiring specificity in the direction-selectivity circuit of the retina
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TLDR
It is shown, 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.Abstract:
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.read more
Citations
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A mesoscale connectome of the mouse brain
Seung Wook Oh,Julie A. Harris,Lydia Ng,Brent Winslow,Nicholas Cain,Stefan Mihalas,Quanxin Wang,Chris Lau,Leonard Kuan,Alex M. Henry,Marty Mortrud,Benjamin Ouellette,Thuc Nghi Nguyen,Staci A. Sorensen,Clifford R. Slaughterbeck,Wayne Wakeman,Yang Li,David Feng,Anh Ho,Eric Nicholas,Karla E. Hirokawa,Phillip Bohn,Kevin M. Joines,Hanchuan Peng,Michael Hawrylycz,John W. Phillips,John G. Hohmann,Paul Wohnoutka,Charles R. Gerfen,Christof Koch,Amy Bernard,Chinh Dang,Allan R. Jones,Hongkui Zeng +33 more
TL;DR: A brain-wide, cellular-level, mesoscale connectome for the mouse, using enhanced green fluorescent protein-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain.
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Structural and molecular interrogation of intact biological systems
Kwanghun Chung,Jenelle Wallace,Sung-Yon Kim,Sandhiya Kalyanasundaram,Aaron S. Andalman,Thomas J. Davidson,Julie J. Mirzabekov,Kelly A. Zalocusky,Joanna Mattis,Aleksandra K. Denisin,Sally Pak,Hannah L. Bernstein,Charu Ramakrishnan,Logan Grosenick,Viviana Gradinaru,Karl Deisseroth +15 more
TL;DR: It is shown that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.
Journal ArticleDOI
Connectomic reconstruction of the inner plexiform layer in the mouse retina
Moritz Helmstaedter,Kevin L. Briggman,Srinivas C. Turaga,Srinivas C. Turaga,Viren Jain,Viren Jain,H. Sebastian Seung,Winfried Denk +7 more
TL;DR: Circuit motifs that emerge from the data indicate a functional mechanism for a known cellular response in a ganglion cell that detects localized motion, and predict that another ganglions cell is motion sensitive.
Journal ArticleDOI
Saturated Reconstruction of a Volume of Neocortex
Narayanan Kasthuri,Kenneth J. Hayworth,Daniel R. Berger,Daniel R. Berger,Richard Schalek,José Angel Conchello,Seymour Knowles-Barley,Dongil Lee,Amelio Vazquez-Reina,Verena Kaynig,Thouis R. Jones,Mike Roberts,Josh Morgan,Juan Carlos Tapia,H. Sebastian Seung,William Gray Roncal,Joshua T. Vogelstein,Randal Burns,Daniel L. Sussman,Carey E. Priebe,Hanspeter Pfister,Jeff W. Lichtman +21 more
TL;DR: In this paper, the authors describe automated technologies to probe the structure of neural tissue at nanometer resolution and use them to generate a saturated reconstruction of a sub-volume of mouse neocortex in which all cellular objects (axons, dendrites, and glia) and many subcellular components (synapses, synaptic vesicles, spines, spine apparati, postsynaptic densities, and mitochondria) are rendered and itemized in a database.
Journal ArticleDOI
TrakEM2 software for neural circuit reconstruction
Albert Cardona,Stephan Saalfeld,Johannes Schindelin,Ignacio Arganda-Carreras,Stephan Preibisch,Mark Longair,Pavel Tomancak,Volker Hartenstein,Rodney J. Douglas +8 more
TL;DR: A software application, TrakEM2, is designed that addresses the systematic reconstruction of neuronal circuits from large electron microscopical and optical image volumes and addresses the challenges of image volume composition from individual, deformed images.
References
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Journal ArticleDOI
Effect of ON pathway blockade on directional selectivity in the rabbit retina
C. A. Kittila,Steve Massey +1 more
TL;DR: Extracellular recordings made from directionally selective (DS) ganglion cells in the rabbit retina during perfusion with 2-amino-4-phosphonobutyric acid (APB) to block ON channels through the retina indicate that simultaneous ON and OFF layer input is not required to generate directional responses in ON-OFF DS ganglions.
Journal ArticleDOI
Dendritic spread and functional coverage of starburst amacrine cells.
TL;DR: Compared the dendritic morphology of starburst amacrine cells in two different strains of mice that differ in starburstAmacrine cell number, the results would suggest that the architecture of the dendedritic network, rather than the overall size of thedendritic field, is dependent on the density of star Burst cells.
Book ChapterDOI
Laminar circuit formation in the vertebrate retina.
TL;DR: The roles of activity-dependent and activity-independent mechanisms in establishing functionally discrete sublaminae in the inner retina, where circuits involving many subtypes of retinal neurons are assembled precisely are contrasted.
Journal ArticleDOI
Starburst cells nondirectionally facilitate the responses of direction-selective retinal ganglion cells
TL;DR: Evidence is presented that the cholinergic outputs of the starburst cells affect the responses of the ganglion cells symmetrically; they provide a feedforward excitation that facilitates the response of the network to movement in both the preferred and null directions.
Journal ArticleDOI
Expression of Alpha 7 nicotinic acetylcholine receptors by bipolar, amacrine, and ganglion cells of the rabbit retina
TL;DR: The data suggest that activation of α7 nAChRs by acetylcholine (ACh) or choline may affect glutamate release from several types of cone bipolar cells, modulating GC responses, and ACh-induced excitation of inhibitory amacrine cells might cause either inhibition or disinhibition of other amacine and GC circuits.
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