Filter
Associated Lab
- Aguilera Castrejon Lab (1) Apply Aguilera Castrejon Lab filter
- Ahrens Lab (46) Apply Ahrens Lab filter
- Aso Lab (39) Apply Aso Lab filter
- Baker Lab (19) Apply Baker Lab filter
- Betzig Lab (99) Apply Betzig Lab filter
- Beyene Lab (5) Apply Beyene Lab filter
- Bock Lab (14) Apply Bock Lab filter
- Branson Lab (45) Apply Branson Lab filter
- Card Lab (34) Apply Card Lab filter
- Cardona Lab (44) Apply Cardona Lab filter
- Chklovskii Lab (10) Apply Chklovskii Lab filter
- Clapham Lab (12) Apply Clapham Lab filter
- Cui Lab (19) Apply Cui Lab filter
- Darshan Lab (8) Apply Darshan Lab filter
- Dickson Lab (32) Apply Dickson Lab filter
- Druckmann Lab (21) Apply Druckmann Lab filter
- Dudman Lab (34) Apply Dudman Lab filter
- Eddy/Rivas Lab (30) Apply Eddy/Rivas Lab filter
- Egnor Lab (4) Apply Egnor Lab filter
- Espinosa Medina Lab (12) Apply Espinosa Medina Lab filter
- Feliciano Lab (6) Apply Feliciano Lab filter
- Fetter Lab (31) Apply Fetter Lab filter
- Fitzgerald Lab (15) Apply Fitzgerald Lab filter
- Freeman Lab (15) Apply Freeman Lab filter
- Funke Lab (35) Apply Funke Lab filter
- Gonen Lab (59) Apply Gonen Lab filter
- Grigorieff Lab (34) Apply Grigorieff Lab filter
- Harris Lab (48) Apply Harris Lab filter
- Heberlein Lab (13) Apply Heberlein Lab filter
- Hermundstad Lab (18) Apply Hermundstad Lab filter
- Hess Lab (69) Apply Hess Lab filter
- Ilanges Lab (1) Apply Ilanges Lab filter
- Jayaraman Lab (40) Apply Jayaraman Lab filter
- Ji Lab (33) Apply Ji Lab filter
- Johnson Lab (1) Apply Johnson Lab filter
- Karpova Lab (13) Apply Karpova Lab filter
- Keleman Lab (8) Apply Keleman Lab filter
- Keller Lab (60) Apply Keller Lab filter
- Koay Lab (1) Apply Koay Lab filter
- Lavis Lab (126) Apply Lavis Lab filter
- Lee (Albert) Lab (29) Apply Lee (Albert) Lab filter
- Leonardo Lab (19) Apply Leonardo Lab filter
- Li Lab (3) Apply Li Lab filter
- Lippincott-Schwartz Lab (89) Apply Lippincott-Schwartz Lab filter
- Liu (Zhe) Lab (56) Apply Liu (Zhe) Lab filter
- Looger Lab (136) Apply Looger Lab filter
- Magee Lab (31) Apply Magee Lab filter
- Menon Lab (12) Apply Menon Lab filter
- Murphy Lab (6) Apply Murphy Lab filter
- O'Shea Lab (5) Apply O'Shea Lab filter
- Otopalik Lab (1) Apply Otopalik Lab filter
- Pachitariu Lab (30) Apply Pachitariu Lab filter
- Pastalkova Lab (5) Apply Pastalkova Lab filter
- Pavlopoulos Lab (7) Apply Pavlopoulos Lab filter
- Pedram Lab (3) Apply Pedram Lab filter
- Podgorski Lab (16) Apply Podgorski Lab filter
- Reiser Lab (43) Apply Reiser Lab filter
- Riddiford Lab (20) Apply Riddiford Lab filter
- Romani Lab (29) Apply Romani Lab filter
- Rubin Lab (101) Apply Rubin Lab filter
- Saalfeld Lab (44) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (36) Apply Scheffer Lab filter
- Schreiter Lab (45) Apply Schreiter Lab filter
- Shroff Lab (24) Apply Shroff Lab filter
- Simpson Lab (18) Apply Simpson Lab filter
- Singer Lab (37) Apply Singer Lab filter
- Spruston Lab (55) Apply Spruston Lab filter
- Stern Lab (69) Apply Stern Lab filter
- Sternson Lab (47) Apply Sternson Lab filter
- Stringer Lab (26) Apply Stringer Lab filter
- Svoboda Lab (131) Apply Svoboda Lab filter
- Tebo Lab (7) Apply Tebo Lab filter
- Tervo Lab (9) Apply Tervo Lab filter
- Tillberg Lab (14) Apply Tillberg Lab filter
- Tjian Lab (17) Apply Tjian Lab filter
- Truman Lab (58) Apply Truman Lab filter
- Turaga Lab (34) Apply Turaga Lab filter
- Turner Lab (24) Apply Turner Lab filter
- Vale Lab (6) Apply Vale Lab filter
- Voigts Lab (2) Apply Voigts Lab filter
- Wang (Meng) Lab (10) Apply Wang (Meng) Lab filter
- Wang (Shaohe) Lab (5) Apply Wang (Shaohe) Lab filter
- Wu Lab (8) Apply Wu Lab filter
- Zlatic Lab (26) Apply Zlatic Lab filter
- Zuker Lab (5) Apply Zuker Lab filter
Associated Project Team
- CellMap (6) Apply CellMap filter
- COSEM (3) Apply COSEM filter
- Fly Descending Interneuron (10) Apply Fly Descending Interneuron filter
- Fly Functional Connectome (14) Apply Fly Functional Connectome filter
- Fly Olympiad (5) Apply Fly Olympiad filter
- FlyEM (51) Apply FlyEM filter
- FlyLight (46) Apply FlyLight filter
- GENIE (40) Apply GENIE filter
- Integrative Imaging (1) Apply Integrative Imaging filter
- Larval Olympiad (2) Apply Larval Olympiad filter
- MouseLight (16) Apply MouseLight filter
- NeuroSeq (1) Apply NeuroSeq filter
- ThalamoSeq (1) Apply ThalamoSeq filter
- Tool Translation Team (T3) (24) Apply Tool Translation Team (T3) filter
- Transcription Imaging (45) Apply Transcription Imaging filter
Associated Support Team
- Project Pipeline Support (1) Apply Project Pipeline Support filter
- Anatomy and Histology (18) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (33) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (13) Apply Electron Microscopy filter
- Gene Targeting and Transgenics (11) Apply Gene Targeting and Transgenics filter
- Integrative Imaging (13) Apply Integrative Imaging filter
- Invertebrate Shared Resource (39) Apply Invertebrate Shared Resource filter
- Janelia Experimental Technology (35) Apply Janelia Experimental Technology filter
- Management Team (1) Apply Management Team filter
- Molecular Genomics (15) Apply Molecular Genomics filter
- Primary & iPS Cell Culture (13) Apply Primary & iPS Cell Culture filter
- Project Technical Resources (37) Apply Project Technical Resources filter
- Quantitative Genomics (19) Apply Quantitative Genomics filter
- Scientific Computing Software (63) Apply Scientific Computing Software filter
- Scientific Computing Systems (6) Apply Scientific Computing Systems filter
- Viral Tools (14) Apply Viral Tools filter
- Vivarium (6) Apply Vivarium filter
Publication Date
- 2024 (170) Apply 2024 filter
- 2023 (170) Apply 2023 filter
- 2022 (166) Apply 2022 filter
- 2021 (174) Apply 2021 filter
- 2020 (177) Apply 2020 filter
- 2019 (177) Apply 2019 filter
- 2018 (206) Apply 2018 filter
- 2017 (186) Apply 2017 filter
- 2016 (191) Apply 2016 filter
- 2015 (195) Apply 2015 filter
- 2014 (190) Apply 2014 filter
- 2013 (136) Apply 2013 filter
- 2012 (112) Apply 2012 filter
- 2011 (98) Apply 2011 filter
- 2010 (61) Apply 2010 filter
- 2009 (56) Apply 2009 filter
- 2008 (40) Apply 2008 filter
- 2007 (21) Apply 2007 filter
- 2006 (3) Apply 2006 filter
2529 Janelia Publications
Showing 2151-2160 of 2529 resultsBiological tissues are rarely transparent, presenting major challenges for deep tissue optical microscopy. The achievable imaging depth is fundamentally limited by wavefront distortions caused by aberration and random scattering. Here, we report an iterative wavefront compensation technique that takes advantage of the nonlinearity of multiphoton signals to determine and compensate for these distortions and to focus light inside deep tissues. Different from conventional adaptive optics methods, this technique can rapidly measure highly complicated wavefront distortions encountered in deep tissue imaging and provide compensations for not only aberration but random scattering. The technique is tested with a variety of highly heterogeneous biological samples including mouse brain tissue, skull, and lymph nodes. We show that high quality three-dimensional imaging can be realized at depths beyond the reach of conventional multiphoton microscopy and adaptive optics methods, albeit over restricted distances for a given correction. Moreover, the required laser excitation power can be greatly reduced in deep tissues, deviating from the power requirement of ballistic light excitation and thus significantly reducing photo damage to the biological tissue.
While it is clear that key transcriptional programmes are important for maintaining pluripotency, the requirement for cell adhesion to the extracellular matrix remains poorly defined. Human pluripotent stem cells (hPSCs) form colonies encircled by an actin ring and large stable cornerstone focal adhesions (FA). Using superresolution two-colour interferometric photo-activated localisation microscopy, we examine the three-dimensional architecture of cornerstone adhesions and report vertical lamination of FA proteins with three main structural features distinct from previously studied focal adhesions: 1) integrin β5 and talin are present at high density, at the edges of cornerstone FA, adjacent to a vertical kank-rich protein wall, 2) vinculin localises higher than previously reported, displaying a head-above-tail orientation, and 3) surprisingly, actin and α-actinin are present in two discrete z-layers. Finally, we report that depletion of kanks diminishes FA patterning, and actin organisation within the colony, indicating a role for kanks in hPSC colony architecture.
Human pluripotent stem cells (hPSC) can generate almost all adult cell lineages. While it is clear that key transcriptional programmes are important elements for maintaining pluripotency, the equally essential requirement for cell adhesion to specific extracellular matrix components remains poorly defined. Our recent observation that hPSC colonies form unusually large “cornerstone” focal adhesions (FA), distinct from parental somatic cells, that are lost following differentiation, emphasises the potential of these atypical FA as gatekeepers of pluripotency. Here, using nanopatterns, we further demonstrate that physical restriction of adhesion size, in hPSC colonies, is sufficient to trigger differentiation. Using superresolution two-colour interfero-metric photo-activated localization microscopy (iPALM), we examined the three-dimensional architecture of these cornerstone adhesions and report vertical lamination of FA proteins with three main structural peculiarities: 1) integrin β5 and talin are present at high density, at the edges of cornerstone FA, adjacent to a vertical kank-rich protein wall. 2) Vinculin localises higher than expected with respect to the substrata and displays a head-above-tail orientation, and 3) surprisingly, actin and α-actinin are present in two discrete layers, a previously undescribed localisation for these proteins. Finally, we report that depletion of kanks diminishes FA patterning, and actin organisation within the colony, indicating a key role for kanks in hPSC colony architecture.
A fundamental objective in molecular biology is to understand how DNA is organized in concert with various proteins, RNA, and biological membranes. Mitochondria maintain and express their own DNA (mtDNA), which is arranged within structures called nucleoids. Their functions, dimensions, composition, and precise locations relative to other mitochondrial structures are poorly defined. Superresolution fluorescence microscopy techniques that exceed the previous limits of imaging within the small and highly compartmentalized mitochondria have been recently developed. We have improved and employed both two- and three-dimensional applications of photoactivated localization microscopy (PALM and iPALM, respectively) to visualize the core dimensions and relative locations of mitochondrial nucleoids at an unprecedented resolution. PALM reveals that nucleoids differ greatly in size and shape. Three-dimensional volumetric analysis indicates that, on average, the mtDNA within ellipsoidal nucleoids is extraordinarily condensed. Two-color PALM shows that the freely diffusible mitochondrial matrix protein is largely excluded from the nucleoid. In contrast, nucleoids are closely associated with the inner membrane and often appear to be wrapped around cristae or crista-like inner membrane invaginations. Determinations revealing high packing density, separation from the matrix, and tight association with the inner membrane underscore the role of mechanisms that regulate access to mtDNA and that remain largely unknown.
Arrays of actin filaments (F-actin) near the apical surface of epithelial cells (medioapical arrays) contribute to apical constriction and morphogenesis throughout phylogeny. Here, superresolution approaches (grazing incidence structured illumination, GI-SIM, and lattice light sheet, LLSM) microscopy resolve individual, fluorescently labeled F-actin and bipolar myosin filaments that drive amnioserosa cell shape changes during dorsal closure in . In expanded cells, F-actin and myosin form loose, apically domed meshworks at the plasma membrane. The arrays condense as cells contract, drawing the domes into the plane of the junctional belts. As condensation continues, individual filaments are no longer uniformly apparent. As cells expand, arrays of actomyosin are again resolved-some F-actin turnover likely occurs, but a large fraction of existing filaments rearrange. In morphologically isotropic cells, actin filaments are randomly oriented and during contraction are drawn together but remain essentially randomly oriented. In anisotropic cells, largely parallel actin filaments are drawn closer to one another. Our images offer unparalleled resolution of F-actin in embryonic tissue, show that medioapical arrays are tightly apposed to the plasma membrane and are continuous with meshworks of lamellar F-actin. Medioapical arrays thereby constitute modified cell cortex. In concert with other tagged array components, superresolution imaging of live specimens will offer new understanding of cortical architecture and function.
BACKGROUND: Previous studies suggest that mechanical feedback could coordinate morphogenetic events in embryos. Furthermore, embryonic tissues have complex structure and composition and undergo large deformations during morphogenesis. Hence we expect highly non-linear and loading-rate dependent tissue mechanical properties in embryos. METHODOLOGY/PRINCIPAL FINDINGS: We used micro-aspiration to test whether a simple linear viscoelastic model was sufficient to describe the mechanical behavior of gastrula stage Xenopus laevis embryonic tissue in vivo. We tested whether these embryonic tissues change their mechanical properties in response to mechanical stimuli but found no evidence of changes in the viscoelastic properties of the tissue in response to stress or stress application rate. We used this model to test hypotheses about the pattern of force generation during electrically induced tissue contractions. The dependence of contractions on suction pressure was most consistent with apical tension, and was inconsistent with isotropic contraction. Finally, stiffer clutches generated stronger contractions, suggesting that force generation and stiffness may be coupled in the embryo. CONCLUSIONS/SIGNIFICANCE: The mechanical behavior of a complex, active embryonic tissue can be surprisingly well described by a simple linear viscoelastic model with power law creep compliance, even at high deformations. We found no evidence of mechanical feedback in this system. Together these results show that very simple mechanical models can be useful in describing embryo mechanics.
The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli. Using cross-correlation analysis, we reveal that the organization of inter-area functional connectivity during visual stimulation mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. We find that four classical hierarchical measures-response latency, receptive-field size, phase-locking to drifting gratings and response decay timescale-are all correlated with the hierarchy. Moreover, recordings obtained during a visual task reveal that the correlation between neural activity and behavioural choice also increases along the hierarchy. Our study provides a foundation for understanding coding and signal propagation across hierarchically organized cortical and thalamic visual areas.
Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviours, preventing the ingestion of toxic substances, and helping to ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste allows the identification of energy-rich nutrients whereas bitter warns against the intake of potentially noxious chemicals. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map, with each taste quality encoded by distinct cortical fields. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal's internal representation, sensory perception, and behavioural actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviours in the absence of sensory input.
During brain development, synapses are initially formed in excess and are later eliminated in an activity-dependent manner, with weak synapses being preferentially removed. Previous studies identified glia as mediators of synapse removal, but it is unclear how glia specifically target weak synapses. Here we show that, in the developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation of caspase-3. Caspase-3 is essential for synapse elimination driven by both spontaneous and experience-dependent neural activity. Synapse weakening-induced caspase-3 activation determines the specificity of synapse elimination mediated by microglia but not astrocytes. Furthermore, in a mouse model of Alzheimer’s disease, caspase-3 deficiency protects against synapse loss induced by amyloid-β deposition. Our results reveal caspase-3 activation as a key step in activity-dependent synapse elimination during development and synapse loss in neurodegeneration.
Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (R(neck)) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that R(neck) is large enough ( 500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by 1.5- to 45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an R(neck)-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons.