Journal ArticleDOI
Wiring specificity in the direction-selectivity circuit of the retina
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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Journal ArticleDOI
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.
Journal ArticleDOI
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
Bulk electroporation and population calcium imaging in the adult mammalian retina
Kevin L. Briggman,Thomas Euler +1 more
TL;DR: An electroporation method to label the complete ganglion cell layer of the adult mammalian retina with a diverse set of indicators with a range of affinities and emission wavelengths that can be combined with transgenic animals expressing fluorescent markers to target specific neuronal types.
Journal ArticleDOI
Is the input to a GABAergic or cholinergic synapse the sole asymmetry in rabbit's retinal directional selectivity?
TL;DR: Examination of the effects of GABAergic and cholinergic antagonists, and anticholinesterases on responses to movement of On-Off directionally selective (DS) ganglion cells of the rabbit's retina found a noncholinergic pathway may be sufficient to account for at least some directional selectivity.
Journal ArticleDOI
Synaptic input to the on-off directionally selective ganglion cell in the rabbit retina.
TL;DR: A physiologically identified on–off directionally selective (DS) ganglion cell with its preferred‐null axis defined was stained with horseradish peroxidase (HRP) and prepared for electron microscopy and a continuous series of thin sections were used to examine the cell's synaptology.
Journal ArticleDOI
Tetrodotoxin-resistant sodium channels contribute to directional responses in starburst amacrine cells
TL;DR: The results indicate that current models of direction-selectivity in the SBACs are inadequate, and suggest that voltage-gated excitatory channels, specifically tetrodotoxin-resistant sodium channels, are important elements in directional signaling.
Journal ArticleDOI
Dendritic relationship between starburst amacrine cells and direction‐selective ganglion cells in the rabbit retina
TL;DR: The dendritic relationship between starburst amacrine cells (SAs) and morphologically and physiologically characterized ON and ON‐OFF direction‐selective ganglion cells (DSGCs) in the rabbit retina was investigated and the computation of motion direction is unlikely to result from apparent asymmetry in geometric proximity between SAs and DSGCs.
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