Filter
Associated Lab
- Aguilera Castrejon Lab (1) Apply Aguilera Castrejon Lab filter
- Ahrens Lab (53) Apply Ahrens Lab filter
- Aso Lab (40) Apply Aso Lab filter
- Baker Lab (19) Apply Baker Lab filter
- Betzig Lab (101) Apply Betzig Lab filter
- Beyene Lab (8) Apply Beyene Lab filter
- Bock Lab (14) Apply Bock Lab filter
- Branson Lab (50) Apply Branson Lab filter
- Card Lab (36) Apply Card Lab filter
- Cardona Lab (45) Apply Cardona Lab filter
- Chklovskii Lab (10) Apply Chklovskii Lab filter
- Clapham Lab (14) 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 (38) Apply Dudman Lab filter
- Eddy/Rivas Lab (30) Apply Eddy/Rivas Lab filter
- Egnor Lab (4) Apply Egnor Lab filter
- Espinosa Medina Lab (15) Apply Espinosa Medina Lab filter
- Feliciano Lab (7) Apply Feliciano Lab filter
- Fetter Lab (31) Apply Fetter Lab filter
- Fitzgerald Lab (16) Apply Fitzgerald Lab filter
- Freeman Lab (15) Apply Freeman Lab filter
- Funke Lab (38) Apply Funke Lab filter
- Gonen Lab (59) Apply Gonen Lab filter
- Grigorieff Lab (34) Apply Grigorieff Lab filter
- Harris Lab (53) Apply Harris Lab filter
- Heberlein Lab (13) Apply Heberlein Lab filter
- Hermundstad Lab (23) Apply Hermundstad Lab filter
- Hess Lab (74) Apply Hess Lab filter
- Ilanges Lab (2) Apply Ilanges Lab filter
- Jayaraman Lab (42) 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 (61) Apply Keller Lab filter
- Koay Lab (2) Apply Koay Lab filter
- Lavis Lab (137) Apply Lavis Lab filter
- Lee (Albert) Lab (29) Apply Lee (Albert) Lab filter
- Leonardo Lab (19) Apply Leonardo Lab filter
- Li Lab (4) Apply Li Lab filter
- Lippincott-Schwartz Lab (97) Apply Lippincott-Schwartz Lab filter
- Liu (Yin) Lab (1) Apply Liu (Yin) Lab filter
- Liu (Zhe) Lab (58) Apply Liu (Zhe) Lab filter
- Looger Lab (137) 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 (6) Apply O'Shea Lab filter
- Otopalik Lab (1) Apply Otopalik Lab filter
- Pachitariu Lab (36) Apply Pachitariu Lab filter
- Pastalkova Lab (5) Apply Pastalkova Lab filter
- Pavlopoulos Lab (7) Apply Pavlopoulos Lab filter
- Pedram Lab (4) Apply Pedram Lab filter
- Podgorski Lab (16) Apply Podgorski Lab filter
- Reiser Lab (45) Apply Reiser Lab filter
- Riddiford Lab (20) Apply Riddiford Lab filter
- Romani Lab (31) Apply Romani Lab filter
- Rubin Lab (105) Apply Rubin Lab filter
- Saalfeld Lab (46) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (36) Apply Scheffer Lab filter
- Schreiter Lab (50) Apply Schreiter Lab filter
- Sgro Lab (1) Apply Sgro Lab filter
- Shroff Lab (31) Apply Shroff Lab filter
- Simpson Lab (18) Apply Simpson Lab filter
- Singer Lab (37) Apply Singer Lab filter
- Spruston Lab (57) Apply Spruston Lab filter
- Stern Lab (73) Apply Stern Lab filter
- Sternson Lab (47) Apply Sternson Lab filter
- Stringer Lab (32) Apply Stringer Lab filter
- Svoboda Lab (131) Apply Svoboda Lab filter
- Tebo Lab (9) Apply Tebo Lab filter
- Tervo Lab (9) Apply Tervo Lab filter
- Tillberg Lab (18) Apply Tillberg Lab filter
- Tjian Lab (17) Apply Tjian Lab filter
- Truman Lab (58) Apply Truman Lab filter
- Turaga Lab (39) Apply Turaga Lab filter
- Turner Lab (27) Apply Turner Lab filter
- Vale Lab (7) Apply Vale Lab filter
- Voigts Lab (3) Apply Voigts Lab filter
- Wang (Meng) Lab (21) Apply Wang (Meng) Lab filter
- Wang (Shaohe) Lab (6) 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 (12) Apply CellMap filter
- COSEM (3) Apply COSEM filter
- FIB-SEM Technology (3) Apply FIB-SEM Technology filter
- Fly Descending Interneuron (11) Apply Fly Descending Interneuron filter
- Fly Functional Connectome (14) Apply Fly Functional Connectome filter
- Fly Olympiad (5) Apply Fly Olympiad filter
- FlyEM (53) Apply FlyEM filter
- FlyLight (49) Apply FlyLight filter
- GENIE (46) Apply GENIE filter
- Integrative Imaging (4) Apply Integrative Imaging filter
- Larval Olympiad (2) Apply Larval Olympiad filter
- MouseLight (18) Apply MouseLight filter
- NeuroSeq (1) Apply NeuroSeq filter
- ThalamoSeq (1) Apply ThalamoSeq filter
- Tool Translation Team (T3) (26) Apply Tool Translation Team (T3) filter
- Transcription Imaging (45) Apply Transcription Imaging filter
Associated Support Team
- Project Pipeline Support (5) Apply Project Pipeline Support filter
- Anatomy and Histology (18) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (36) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (16) Apply Electron Microscopy filter
- Gene Targeting and Transgenics (11) Apply Gene Targeting and Transgenics filter
- Integrative Imaging (17) Apply Integrative Imaging filter
- Invertebrate Shared Resource (40) Apply Invertebrate Shared Resource filter
- Janelia Experimental Technology (37) Apply Janelia Experimental Technology filter
- Management Team (1) Apply Management Team filter
- Molecular Genomics (15) Apply Molecular Genomics filter
- Primary & iPS Cell Culture (14) Apply Primary & iPS Cell Culture filter
- Project Technical Resources (50) Apply Project Technical Resources filter
- Quantitative Genomics (19) Apply Quantitative Genomics filter
- Scientific Computing Software (92) Apply Scientific Computing Software filter
- Scientific Computing Systems (7) Apply Scientific Computing Systems filter
- Viral Tools (14) Apply Viral Tools filter
- Vivarium (7) Apply Vivarium filter
Publication Date
- 2025 (126) Apply 2025 filter
- 2024 (215) Apply 2024 filter
- 2023 (159) Apply 2023 filter
- 2022 (167) Apply 2022 filter
- 2021 (175) 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
2691 Janelia Publications
Showing 121-130 of 2691 resultsAnimals need to rapidly learn to recognize and avoid predators. This ability may be especially important for young animals due to their increased vulnerability. It is unknown whether, and how, nascent vertebrates are capable of such rapid learning. Here, we used a robotic predator-prey interaction assay to show that 1 week after fertilization-a developmental stage where they have approximately 1% the number of neurons of adults-zebrafish larvae rapidly and robustly learn to recognize a stationary object as a threat after the object pursues the fish for ∼1 min. Larvae continue to avoid the threatening object after it stops moving and can learn to distinguish threatening from non-threatening objects of a different color. Whole-brain functional imaging revealed the multi-timescale activity of noradrenergic neurons and forebrain circuits that encoded the threat. Chemogenetic ablation of those populations prevented the learning. Thus, a noradrenergic and forebrain multiregional network underlies the ability of young vertebrates to rapidly learn to recognize potential predators within their first week of life.
Effective classification of neuronal cell types requires both molecular and morphological descriptors to be collected in situ at single cell resolution. However, current spatial transcriptomics techniques are not compatible with imaging workflows that successfully reconstruct the morphology of complete axonal projections. Here, we introduce a new methodology that combines tissue clearing, submicron whole-brain two photon imaging, and Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to assign molecular identities to fully reconstructed neurons in the mouse brain, which we call morphoFISH. We used morphoFISH to molecularly identify a previously unknown population of cingulate neurons projecting ipsilaterally to the dorsal striatum and contralaterally to higher-order thalamus. By pairing whole-brain morphometry, improved techniques for nucleic acid preservation and spatial gene expression, morphoFISH offers a quantitative solution for discovery of multimodal cell types and complements existing techniques for characterization of increasingly fine-grained cellular heterogeneity in brain circuits.Competing Interest StatementThe authors have declared no competing interest.
The regular distribution of mitochondrial DNA-containing nucleoids is essential for mitochondrial function and genome inheritance; however, the underlying mechanisms remain unknown. Our data reveal that mitochondria frequently undergo spontaneous and reversible pearling - a biophysical instability in which tubules undulate into regularly spaced beads. We discovered that pearling imposes a characteristic length scale, simultaneously mediating nucleoid disaggregation and establishing inter-nucleoid distancing with near-maximally achievable precision. Cristae invaginations play a dual role: lamellar cristae density determines pearling frequency and duration, and preserves the resulting nucleoid spacing after recovery. The distribution of mitochondrial genomes is thus fundamentally governed by the interplay between spontaneous pearling and cristae ultrastructure.
Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca modulatory machinery, facilitating signal transmission and ryanodine-receptor-dependent Ca release at ER-PM junctions over 20 μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.
Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles. Here, we identify molecular changes that accompany cilia deconstruction and centriole docking in GC neurons. We used single cell transcriptomic and immunocytological analyses to compare the transcript levels and subcellular localization of proteins between progenitor, differentiating, and mature GCs. Differentiating GCs lacked transcripts for key activators of premitotic cilia resorption, indicating that cilia disassembly in differentiating cells is distinct from premitotic cilia resorption. Instead, during differentiation, transcripts of many genes required for cilia maintenance-specifically those encoding components of intraflagellar transport, pericentrosomal material, and centriolar satellites-decreased. The abundance of several corresponding proteins in and around cilia and centrosomes also decreased. These changes coincided with downregulation of SHH signaling prior to differentiation, even in a mutant with excessive SHH activation. Finally, mother centrioles in maturing granule neurons recruited the cap complex protein, CEP97. These data suggest that a global, developmentally programmed decrease in cilium maintenance in differentiating GCs mediates cilia deconstruction, while capping of docked mother centrioles prevents cilia regrowth and dysregulated SHH signaling. Our study provides mechanistic insights expanding our understanding of permanent cilia loss in multiple tissue-specific contexts.
Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat-to-neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan-extending lipid chaperone, lipid binding protein-3 (LBP-3), which shuttles dihomo-γ-linolenic (DGLA) acid from intestinal fat to neurons. We present the first high-resolution crystal structure of LBP-3, which reveals a classic iLBP fold with an unexpected and unique homodimeric arrangement via interstrand interactions that is incompatible with ligand binding. We identify key ionic interactions that mediate DGLA binding within the lipid binding pocket. Molecular dynamics simulations further elucidate LBP-3's preferential binding to DGLA due to its rotational freedom and access to favorable binding conformations compared to other 20-carbon PUFAs. We also propose that LBP-3 dimerization may be a unique regulatory mechanism for lipid chaperones.
Animals need to rapidly learn to recognize and avoid predators. This ability may be especially important for young animals due to their increased vulnerability. It is unknown whether, and how, nascent vertebrates are capable of such rapid learning. Here, we used a robotic predator-prey interaction assay to show that 1 week after fertilization-a developmental stage where they have approximately 1% the number of neurons of adults-zebrafish larvae rapidly and robustly learn to recognize a stationary object as a threat after the object pursues the fish for ∼1 min. Larvae continue to avoid the threatening object after it stops moving and can learn to distinguish threatening from non-threatening objects of a different color. Whole-brain functional imaging revealed the multi-timescale activity of noradrenergic neurons and forebrain circuits that encoded the threat. Chemogenetic ablation of those populations prevented the learning. Thus, a noradrenergic and forebrain multiregional network underlies the ability of young vertebrates to rapidly learn to recognize potential predators within their first week of life.
The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports a RIPK1 degrader that serves as a chemical probe for investigating the scaffolding functions of RIPK1 and as a potential therapeutic agent to enhance tumor responses to ICBs therapy.
Transient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the "giving-up" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity. After ketamine washout, this circuit exhibits hyposensitivity to futility, leading to long-term increased perseverance. Pharmacological, chemogenetic, and optogenetic manipulations show that norepinephrine and astrocytes are necessary and sufficient for ketamine's long-term perseverance-enhancing aftereffects. In vivo calcium imaging revealed that astrocytes in adult mouse cortex are similarly activated during futility in the tail suspension test and that acute ketamine exposure also induces astrocyte hyperactivation. The cross-species conservation of ketamine's modulation of noradrenergic-astroglial circuits and evidence that plasticity in this pathway can alter the behavioral response to futility hold promise for identifying new strategies to treat affective disorders.
Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA), has been described as a chemical chaperone. While promising in models of protein folding diseases, TUDCA's mechanism of action remains unclear. Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or over-expression of a misfolded mutant secretory protein. Neither pretreatment with or delayed addition of TUDCA conferred protection against Tm. Importantly, attenuation of Tm-induced toxicity required TUDCA's critical micelle forming concentration, suggesting a mechanism where TUDCA directly sequesters drugs. Indeed, in several assays, TUDCA treated cells closely resembled cells treated with lower doses of Tm. In addition, we found TUDCA can inhibit dyes from labeling intracellular compartments. Thus, our study challenges the model of TUDCA as a chemical chaperone and suggests that TUDCA decreases drug bioavailability, allowing cells to adapt to ER stress.