Filter
Associated Lab
- Ahrens Lab (4) Apply Ahrens Lab filter
- Aso Lab (4) Apply Aso Lab filter
- Betzig Lab (6) Apply Betzig Lab filter
- Bock Lab (3) Apply Bock Lab filter
- Branson Lab (5) Apply Branson Lab filter
- Card Lab (4) Apply Card Lab filter
- Cardona Lab (6) Apply Cardona Lab filter
- Clapham Lab (4) Apply Clapham Lab filter
- Darshan Lab (1) Apply Darshan Lab filter
- Dickson Lab (2) Apply Dickson Lab filter
- Druckmann Lab (4) Apply Druckmann Lab filter
- Dudman Lab (3) Apply Dudman Lab filter
- Feliciano Lab (1) Apply Feliciano Lab filter
- Fetter Lab (4) Apply Fetter Lab filter
- Fitzgerald Lab (1) Apply Fitzgerald Lab filter
- Freeman Lab (1) Apply Freeman Lab filter
- Funke Lab (4) Apply Funke Lab filter
- Gonen Lab (9) Apply Gonen Lab filter
- Grigorieff Lab (5) Apply Grigorieff Lab filter
- Harris Lab (5) Apply Harris Lab filter
- Heberlein Lab (3) Apply Heberlein Lab filter
- Hermundstad Lab (1) Apply Hermundstad Lab filter
- Hess Lab (3) Apply Hess Lab filter
- Jayaraman Lab (3) Apply Jayaraman Lab filter
- Ji Lab (5) Apply Ji Lab filter
- Karpova Lab (2) Apply Karpova Lab filter
- Keleman Lab (1) Apply Keleman Lab filter
- Keller Lab (6) Apply Keller Lab filter
- Lavis Lab (12) Apply Lavis Lab filter
- Lee (Albert) Lab (2) Apply Lee (Albert) Lab filter
- Lippincott-Schwartz Lab (11) Apply Lippincott-Schwartz Lab filter
- Liu (Zhe) Lab (3) Apply Liu (Zhe) Lab filter
- Looger Lab (8) Apply Looger Lab filter
- Magee Lab (1) Apply Magee Lab filter
- Menon Lab (1) Apply Menon Lab filter
- Murphy Lab (1) Apply Murphy Lab filter
- Pachitariu Lab (2) Apply Pachitariu Lab filter
- Pavlopoulos Lab (2) Apply Pavlopoulos Lab filter
- Podgorski Lab (2) Apply Podgorski Lab filter
- Reiser Lab (4) Apply Reiser Lab filter
- Riddiford Lab (1) Apply Riddiford Lab filter
- Romani Lab (3) Apply Romani Lab filter
- Rubin Lab (7) Apply Rubin Lab filter
- Saalfeld Lab (5) Apply Saalfeld Lab filter
- Scheffer Lab (4) Apply Scheffer Lab filter
- Schreiter Lab (4) Apply Schreiter Lab filter
- Singer Lab (5) Apply Singer Lab filter
- Spruston Lab (8) Apply Spruston Lab filter
- Stern Lab (6) Apply Stern Lab filter
- Stringer Lab (1) Apply Stringer Lab filter
- Svoboda Lab (11) Apply Svoboda Lab filter
- Tervo Lab (2) Apply Tervo Lab filter
- Tillberg Lab (1) Apply Tillberg Lab filter
- Truman Lab (8) Apply Truman Lab filter
- Turaga Lab (7) Apply Turaga Lab filter
- Zlatic Lab (5) Apply Zlatic Lab filter
Associated Project Team
Associated Support Team
- Anatomy and Histology (3) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (6) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (1) Apply Electron Microscopy filter
- Fly Facility (1) Apply Fly Facility filter
- Gene Targeting and Transgenics (3) Apply Gene Targeting and Transgenics filter
- Janelia Experimental Technology (4) Apply Janelia Experimental Technology filter
- Quantitative Genomics (4) Apply Quantitative Genomics filter
- Scientific Computing Software (9) Apply Scientific Computing Software filter
- Vivarium (2) Apply Vivarium filter
Publication Date
- December 2018 (13) Apply December 2018 filter
- November 2018 (18) Apply November 2018 filter
- October 2018 (25) Apply October 2018 filter
- September 2018 (12) Apply September 2018 filter
- August 2018 (23) Apply August 2018 filter
- July 2018 (14) Apply July 2018 filter
- June 2018 (20) Apply June 2018 filter
- May 2018 (16) Apply May 2018 filter
- April 2018 (22) Apply April 2018 filter
- March 2018 (19) Apply March 2018 filter
- February 2018 (12) Apply February 2018 filter
- January 2018 (12) Apply January 2018 filter
- Remove 2018 filter 2018
206 Janelia Publications
Showing 21-30 of 206 resultsDown syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability.
Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes.
Animals strategically scan the environment to form an accurate perception of their surroundings. Here we investigated the neuronal representations that mediate this behavior. Ca imaging and selective optogenetic manipulation during an active sensing task reveals that layer 5 pyramidal neurons in the vibrissae cortex produce a diverse and distributed representation that is required for mice to adapt their whisking motor strategy to changing sensory cues. The optogenetic perturbation degraded single-neuron selectivity and network population encoding through a selective inhibition of active dendritic integration. Together the data indicate that active dendritic integration in pyramidal neurons produces a nonlinearly mixed network representation of joint sensorimotor parameters that is used to transform sensory information into motor commands during adaptive behavior. The prevalence of the layer 5 cortical circuit motif suggests that this is a general circuit computation.
Behavior relies on the ability of sensory systems to infer properties of the environment from incoming stimuli. The accuracy of inference depends on the fidelity with which behaviorally relevant properties of stimuli are encoded in neural responses. High-fidelity encodings can be metabolically costly, but low-fidelity encodings can cause errors in inference. Here, we discuss general principles that underlie the tradeoff between encoding cost and inference error. We then derive adaptive encoding schemes that dynamically navigate this tradeoff. These optimal encodings tend to increase the fidelity of the neural representation following a change in the stimulus distribution, and reduce fidelity for stimuli that originate from a known distribution. We predict dynamical signatures of such encoding schemes and demonstrate how known phenomena, such as burst coding and firing rate adaptation, can be understood as hallmarks of optimal coding for accurate inference.
Highlights: With the ability to correct for the aberrations introduced by biological specimens, adaptive optics—a method originally developed for astronomical telescopes—has been applied to optical microscopy to recover diffraction-limited imaging performance deep within living tissue. In particular, this technology has been used to improve image quality and provide a more accurate characterization of both structure and function of neurons in a variety of living organisms. Among its many highlights, adaptive optical microscopy has made it possible to image large volumes with diffraction-limited resolution in zebrafish larval brains, to resolve dendritic spines over 600μm deep in the mouse brain, and to more accurately characterize the orientation tuning properties of thalamic boutons in the primary visual cortex of awake mice.
Seven neuropeptides are expressed within the Drosophila brain circadian network. Our previous mRNA profiling suggested that Allatostatin-C (AstC) is an eighth neuropeptide and specifically expressed in dorsal clock neurons (DN1s). Our results here show that AstC is, indeed, expressed in DN1s, where it oscillates. AstC is also expressed in two less well-characterized circadian neuronal clusters, the DN3s and lateral-posterior neurons (LPNs). Behavioral experiments indicate that clock-neuron-derived AstC is required to mediate evening locomotor activity under short (winter-like) and long (summer-like) photoperiods. The AstC-Receptor 2 (AstC-R2) is expressed in LNds, the clock neurons that drive evening locomotor activity, and AstC-R2 is required in these neurons to modulate the same short photoperiod evening phenotype. Ex vivo calcium imaging indicates that AstC directly inhibits a single LNd. The results suggest that a novel AstC/AstC-R2 signaling pathway, from dorsal circadian neurons to an LNd, regulates the evening phase in Drosophila.
The fruit fly Drosophila melanogaster is an important model organism for neuroscience with a wide array of genetic tools that enable the mapping of individuals neurons and neural subtypes. Brain templates are essential for comparative biological studies because they enable analyzing many individuals in a common reference space. Several central brain templates exist for Drosophila, but every one is either biased, uses sub-optimal tissue preparation, is imaged at low resolution, or does not account for artifacts. No publicly available Drosophila ventral nerve cord template currently exists. In this work, we created high-resolution templates of the Drosophila brain and ventral nerve cord using the best-available technologies for imaging, artifact correction, stitching, and template construction using groupwise registration. We evaluated our central brain template against the four most competitive, publicly available brain templates and demonstrate that ours enables more accurate registration with fewer local deformations in shorter time.
Single-particle electron cryo-microscopy and computational image classification can be used to analyze structural variability in macromolecules and their assemblies. In some cases, a particle may contain different regions that each display a range of distinct conformations. We have developed strategies, implemented within the Frealign and cisTEM image processing packages, to focus classify on specific regions of a particle and detect potential covariance. The strategies are based on masking the region of interest using either a 2-D mask applied to reference projections and particle images, or a 3-D mask applied to the 3-D volume. We show that focused classification approaches can be used to study structural covariance, a concept that is likely to gain more importance as datasets grow in size, allowing the distinction of more structural states and smaller differences between states. Finally, we apply the approaches to an experimental dataset containing the HIV-1 Transactivation Response (TAR) element RNA fused into the large bacterial ribosomal subunit to deconvolve structural mobility within localized regions of interest, and to a dataset containing assembly intermediates of the large subunit to measure structural covariance.
Micro-crystal electron diffraction (MicroED) combines the efficiency of electron scattering with diffraction to allow structure determination from nano-sized crystalline samples in cryoelectron microscopy (cryo-EM). It has been used to solve structures of a diverse set of biomolecules and materials, in some cases to sub-atomic resolution. However, little is known about the damaging effects of the electron beam on samples during such measurements. We assess global and site-specific damage from electron radiation on nanocrystals of proteinase K and of a prion hepta-peptide and find that the dynamics of electron-induced damage follow well-established trends observed in X-ray crystallography. Metal ions are perturbed, disulfide bonds are broken, and acidic side chains are decarboxylated while the diffracted intensities decay exponentially with increasing exposure. A better understanding of radiation damage in MicroED improves our assessment and processing of all types of cryo-EM data.
The ability of fluorescence microscopy to simultaneously image multiple specific molecules of interest has allowed biologists to infer macromolecular organization and colocalization in fixed and live samples. However, a number of factors could affect these analyses, and colocalization is a misnomer. We propose that image similarity coefficient as a better and more descriptive term. In this chapter we will discuss many of the factors involved with determining image similarity including our perception of color in images. In addition, the correct use of several commonly accepted methods such as Pearson’s correlation coefficient, Manders’ overlap coefficient, and Spearman’s ranked correlation coefficient is discussed.