57 results on '"Wei-Chung Allen Lee"'
Search Results
2. Wiring variations that enable and constrain neural computation in a sensory microcircuit
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William F Tobin, Rachel I Wilson, and Wei-Chung Allen Lee
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electron microscopy ,olfaction ,circuit variability ,compensation ,compartmental modeling ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Neural network function can be shaped by varying the strength of synaptic connections. One way to achieve this is to vary connection structure. To investigate how structural variation among synaptic connections might affect neural computation, we examined primary afferent connections in the Drosophila olfactory system. We used large-scale serial section electron microscopy to reconstruct all the olfactory receptor neuron (ORN) axons that target a left-right pair of glomeruli, as well as all the projection neurons (PNs) postsynaptic to these ORNs. We found three variations in ORN→PN connectivity. First, we found a systematic co-variation in synapse number and PN dendrite size, suggesting total synaptic conductance is tuned to postsynaptic excitability. Second, we discovered that PNs receive more synapses from ipsilateral than contralateral ORNs, providing a structural basis for odor lateralization behavior. Finally, we found evidence of imprecision in ORN→PN connections that can diminish network performance.
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- 2017
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3. Correction: Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex.
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Wei-Chung Allen Lee, Hayden Huang, Guoping Feng, Joshua R Sanes, Emery N Brown, Peter T So, and Elly Nedivi
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Biology (General) ,QH301-705.5 - Abstract
Chronic in vivo imaging of fluorescent-labeled neurons in adult mice reveals extension and retraction of dendrites in GABAergic non-pyramidal interneurons of the cerebral cortex.
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- 2006
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4. Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex.
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Wei-Chung Allen Lee, Hayden Huang, Guoping Feng, Joshua R Sanes, Emery N Brown, Peter T So, and Elly Nedivi
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Biology (General) ,QH301-705.5 - Abstract
Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. To examine the extent of neuronal remodeling that occurs in the brain on a day-to-day basis, we used a multiphoton-based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here we show the first unambiguous evidence (to our knowledge) of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA-positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and they suggest that circuit rearrangement in the adult cortex is restricted by cell type-specific rules.
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- 2006
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5. X-Ray2EM: Uncertainty-Aware Cross-Modality Image Reconstruction from X-Ray to Electron Microscopy in Connectomics.
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Yicong Li 0002, Yaron Meirovitch, Aaron T. Kuan, Jasper S. Phelps, Alexandra Pacureanu, Wei-Chung Allen Lee 0001, Nir Shavit, and Lu Mi
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- 2023
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6. Unpaired Image Enhancement for Neurite Segmentation in x-ray Tomography.
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Jeff L. Rhoades, Arlo Sheridan, Mukul Narwani, Brian Reicher, Mark Larson, Shuhan Xie, Tri Nguyen, Aaron T. Kuan, Alexandra Pacureanu, Wei-Chung Allen Lee 0001, and Jan Funke
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- 2023
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7. Removing Imaging Artifacts in Electron Microscopy using an Asymmetrically Cyclic Adversarial Network without Paired Training Data.
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Tran Minh Quan, David Grant Colburn Hildebrand, Kanggeun Lee, Logan A. Thomas, Aaron T. Kuan, Wei-Chung Allen Lee 0001, and Won-Ki Jeong
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- 2019
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8. ssEMnet: Serial-Section Electron Microscopy Image Registration Using a Spatial Transformer Network with Learned Features.
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Inwan Yoo, David G. C. Hildebrand, Willie F. Tobin, Wei-Chung Allen Lee 0001, and Won-Ki Jeong
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- 2017
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9. Structured cerebellar connectivity supports resilient pattern separation
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Tri M. Nguyen, Logan A. Thomas, Jeff L. Rhoades, Ilaria Ricchi, Xintong Cindy Yuan, Arlo Sheridan, David G. C. Hildebrand, Jan Funke, Wade G. Regehr, and Wei-Chung Allen Lee
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mechanisms ,encode ,cortex ,Multidisciplinary ,annotation ,circuits ,synchrony ,synapses ,organization ,purkinje-cell ,Article ,granule cells - Abstract
The cerebellum is thought to help detect and correct errors between intended and executed commands(1,2) and is critical for social behaviours, cognition and emotion 3 Computations for motor control must be performed quicklyto correct errors in real time and should be sensitive to small differences between patterns for fine error correction while being resilient to noise(7). Influential theories of cerebellar information processing have largely assumed random network connectivity, which increases the encoding capacity ofthe network's first layer(8-)(13). However, maximizing encoding capacity reduces the resilience to noise(7). To understand how neuronal circuits address this fundamental trade-off, we mapped the feedforward connectivity in the mouse cerebellar cortex using automated large-scale transmission electron microscopy and convolutional neural network-based image segmentation. We found that both the input and output layers ofthe circuit exhibit redundant and selective connectivity motifs, which contrast with prevailing models. Numerical simulations suggest that these redundant, non-random connectivity motifs increase the resilience to noise at a negligible cost to the overall encoding capacity. This work reveals how neuronal network structure can support a trade-off between encoding capacity and redundancy, unveiling principles of biological network architecture with implications for the design of artificial neural networks.
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- 2022
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10. Whole-brain serial-section electron microscopy in larval zebrafish.
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David Grant Colburn Hildebrand, Marcelo Cicconet, Russel Miguel Torres, Woohyuk Choi, Tran Minh Quan, Jungmin Moon, Arthur W. Wetzel, Andrew Scott Champion, Brett J. Graham, Owen Randlett, George S. Plummer, Ruben Portugues, Isaac Henry Bianco, Stephan Saalfeld, Alexander D. Baden, Kunal Lillaney, Randal C. Burns, Joshua T. Vogelstein, Alexander Schier, Wei-Chung Allen Lee 0001, Won-Ki Jeong, Jeff William Lichtman, and Florian Engert
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- 2017
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11. Synaptic architecture of leg and wing motor control networks in Drosophila
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Ellen Lesser, Anthony W. Azevedo, Jasper S. Phelps, Leila Elabbady, Andrew P. Cook, Brandon Mark, Sumiya Kuroda, Anne Sustar, Anthony J. Moussa, Chris J. Dallmann, Sweta Agrawal, Su-Yee J. Lee, Brandon G. Pratt, Kyobi Skutt-Kakari, Stephan Gerhard, Ran Lu, Nico Kemnitz, Kisuk Lee, Akhilesh Halageri, Manuel Castro, Dodam Ih, Jay Gager, Marwan Tammam, Sven Dorkenwald, Forrest C. Collman, Casey M Schneider-Mizell, Derrick Brittain, Chris S Jordan, H Sebastian Seung, Thomas Macrina, Michael H Dickinson, Wei-Chung Allen Lee, and John C. Tuthill
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Article - Abstract
Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling theDrosophilaleg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.
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- 2023
12. Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties
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Tomas Osorno, Stephanie Rudolph, Tri Nguyen, Velina Kozareva, Naeem M. Nadaf, Aliya Norton, Evan Z. Macosko, Wei-Chung Allen Lee, and Wade G. Regehr
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Neurons ,Cerebellar Cortex ,Mice ,Purkinje Cells ,Interneurons ,Cerebellum ,General Neuroscience ,Animals - Abstract
To understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections and function remain unknown. Here, we clarify these properties using electrophysiology, single-nucleus RNA sequencing, in situ hybridization and serial electron microscopy in mice. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells and are strongly inhibited by PCs. CCs in turn primarily inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals converge onto CCs to allow them to assume a unique role in controlling cerebellar output.
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- 2022
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13. Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch
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Annie Handler, Qiyu Zhang, Song Pang, Tri M. Nguyen, Michael Iskols, Michael Nolan-Tamariz, Stuart Cattel, Rebecca Plumb, Brianna Sanchez, Karyl Ashjian, Aria Shotland, Bartianna Brown, Madiha Kabeer, Josef Turecek, Genelle Rankin, Wangchu Xiang, Elisa C. Pavarino, Nusrat Africawala, Celine Santiago, Wei-Chung Allen Lee, C. Shan Xu, and David D. Ginty
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Article - Abstract
Specialized mechanosensory end organs within mammalian skin—hair follicle-associated lanceolate complexes, Meissner corpuscles, and Pacinian corpuscles—enable our perception of light, dynamic touch1. In each of these end organs, fast-conducting mechanically sensitive neurons, called Aβ low-threshold mechanoreceptors (Aβ LTMRs), associate with resident glial cells, known as terminal Schwann cells (TSCs) or lamellar cells, to form complex axon ending structures. Lanceolate-forming and corpuscle-innervating Aβ LTMRs share a low threshold for mechanical activation, a rapidly adapting (RA) response to force indentation, and high sensitivity to dynamic stimuli1–6. How mechanical stimuli lead to activation of the requisite mechanotransduction channel Piezo27–15and Aβ RA-LTMR excitation across the morphologically dissimilar mechanosensory end organ structures is not understood. Here, we report the precise subcellular distribution of Piezo2 and high-resolution, isotropic 3D reconstructions of all three end organs formed by Aβ RA-LTMRs determined by large volume enhanced Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) imaging. We found that within each end organ, Piezo2 is enriched along the sensory axon membrane and is minimally or not expressed in TSCs and lamellar cells. We also observed a large number of small cytoplasmic protrusions enriched along the Aβ RA-LTMR axon terminals associated with hair follicles, Meissner corpuscles, and Pacinian corpuscles. These axon protrusions reside within close proximity to axonal Piezo2, occasionally contain the channel, and often form adherens junctions with nearby non-neuronal cells. Our findings support a unified model for Aβ RA-LTMR activation in which axon protrusions anchor Aβ RA-LTMR axon terminals to specialized end organ cells, enabling mechanical stimuli to stretch the axon in hundreds to thousands of sites across an individual end organ and leading to activation of proximal Piezo2 channels and excitation of the neuron.
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- 2023
14. Tools for comprehensive reconstruction and analysis ofDrosophilamotor circuits
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Anthony Azevedo, Ellen Lesser, Brandon Mark, Jasper Phelps, Leila Elabbady, Sumiya Kuroda, Anne Sustar, Anthony Moussa, Avinash Kandelwal, Chris J. Dallmann, Sweta Agrawal, Su-Yee J. Lee, Brandon Pratt, Andrew Cook, Kyobi Skutt-Kakaria, Stephan Gerhard, Ran Lu, Nico Kemnitz, Kisuk Lee, Akhilesh Halageri, Manuel Castro, Dodam Ih, Jay Gager, Marwan Tammam, Sven Dorkenwald, Forrest Collman, Casey Schneider-Mizell, Derrick Brittain, Chris S. Jordan, Michael Dickinson, Alexandra Pacureanu, H. Sebastian Seung, Thomas Macrina, Wei-Chung Allen Lee, and John C. Tuthill
- Abstract
Like the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we applied automated tools for electron microscopy (EM) volume alignment, neuron reconstruction, and synapse prediction to create a draft connectome of theDrosophilaVNC. To interpret the VNC connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and x-ray holographic nano-tomography volumes of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings with the middle and front legs during escape takeoff. We provide the draft VNC connectome and motor neuron atlas, along with tools for programmatic and interactive access, as community resources.
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- 2022
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15. Origins of proprioceptor feature selectivity and topographic maps in theDrosophilaleg
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Akira Mamiya, Anne Sustar, Igor Siwanowicz, Yanyan Qi, Tzu-Chiao Lu, Pralaksha Gurung, Chenghao Chen, Jasper S. Phelps, Aaron T. Kuan, Alexandra Pacureanu, Wei-Chung Allen Lee, Hongjie Li, Natasha Mhatre, and John C. Tuthill
- Abstract
Our ability to sense and move our bodies relies on proprioceptors, sensory neurons that detect mechanical forces within the body. Proprioceptors are diverse: different subtypes detect different features of joint kinematics, such as position, directional movement, and vibration. However, because they are located within complex and dynamic peripheral tissues, the underlying mechanisms of proprioceptor feature selectivity remain poorly understood. Here, we investigate molecular and biomechanical contributions to proprioceptor diversity in theDrosophilaleg. Using single-nucleus RNA sequencing, we found that different proprioceptor subtypes express similar complements of mechanosensory and other ion channels. However, anatomical reconstruction of the proprioceptive organ and connected tendons revealed major biomechanical differences between proprioceptor subtypes. We constructed a computational model of the proprioceptors and tendons, which identified a putative biomechanical mechanism for joint angle selectivity. The model also predicted the existence of a goniotopic map of joint angle among position-tuned proprioceptors, which we confirmed using calcium imaging. Our findings suggest that biomechanical specialization is a key determinant of proprioceptor feature selectivity inDrosophila. More broadly, our discovery of proprioceptive maps in the fly leg reveals common organizational principles between proprioception and other topographically organized sensory systems.
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- 2022
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16. Automatic detection of synaptic partners in a whole-brain Drosophila electron microscopy data set
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Tri Nguyen, Jan Funke, Stephan Gerhard, Rachel Wilson, Tom Kazimiers, Philipp Schlegel, Wei-Chung Allen Lee, Renate Krause, Larissa Heinrich, Davi D. Bock, Caroline Malin-Mayor, Srinivas C. Turaga, Arlo Sheridan, Gregory S.X.E. Jefferis, Julia Buhmann, Stephan Saalfeld, and Matthew Cook
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0303 health sciences ,Computer science ,business.industry ,fungi ,Connectivity graph ,Pattern recognition ,Cell Biology ,Biochemistry ,law.invention ,Data set ,03 medical and health sciences ,Identification (information) ,law ,Artificial intelligence ,User interface ,Electron microscope ,business ,Molecular Biology ,030304 developmental biology ,Biotechnology - Abstract
We develop an automatic method for synaptic partner identification in insect brains and use it to predict synaptic partners in a whole-brain electron microscopy dataset of the fruit fly. The predictions can be used to infer a connectivity graph with high accuracy, thus allowing fast identification of neural pathways. To facilitate circuit reconstruction using our results, we develop CIRCUITMAP, a user interface add-on for the circuit annotation tool CATMAID. A deep-learning-based approach enables automatic identification of synaptically connected neurons in electron microscopy datasets of the fly brain.
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- 2021
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17. Multiplexed peroxidase-based electron microscopy labeling enables simultaneous visualization of multiple cell types
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Wei-Chung Allen Lee, David D. Ginty, David L. Paul, and Qiyu Zhang
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0301 basic medicine ,Nervous system ,Cell type ,Confocal ,Genetic Vectors ,Mice, Transgenic ,Signal-To-Noise Ratio ,Inhibitory postsynaptic potential ,Multiplexing ,Article ,Adenoviridae ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Genes, Reporter ,law ,Microscopy ,medicine ,Animals ,Neurons, Afferent ,Cerebral Cortex ,Neurons ,Microscopy, Confocal ,biology ,Chemistry ,General Neuroscience ,Immunohistochemistry ,Cell biology ,Posterior Horn Cells ,Microscopy, Electron ,030104 developmental biology ,medicine.anatomical_structure ,Peroxidases ,Synapses ,biology.protein ,Electron microscope ,Neuroscience ,030217 neurology & neurosurgery ,Peroxidase - Abstract
Electron microscopy (EM) is a powerful tool for circuit mapping, but identifying specific cell types in EM datasets remains a major challenge. Here we describe a technique enabling simultaneous visualization of multiple genetically identified neuronal populations so that synaptic interactions between them can be unequivocally defined. We present 15 adeno-associated virus constructs and 6 mouse reporter lines for multiplexed EM labeling in the mammalian nervous system. These reporters feature dAPEX2, which exhibits dramatically improved signal compared with previously described ascorbate peroxidases. By targeting this enhanced peroxidase to different subcellular compartments, multiple orthogonal reporters can be simultaneously visualized and distinguished under EM using a protocol compatible with existing EM pipelines. Proof-of-principle double and triple EM labeling experiments demonstrated synaptic connections between primary afferents, descending cortical inputs, and inhibitory interneurons in the spinal cord dorsal horn. Our multiplexed peroxidase-based EM labeling system should therefore greatly facilitate analysis of connectivity in the nervous system.
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- 2019
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18. Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development
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Yajun Xie, Aaron T. Kuan, Wengang Wang, Zachary T. Herbert, Olivia Mosto, Olubusola Olukoya, Manal Adam, Steve Vu, Minsu Kim, Diana Tran, Nicolás Gómez, Claire Charpentier, Ingie Sorour, Tiara E. Lacey, Michael Y. Tolstorukov, Bernardo L. Sabatini, Wei-Chung Allen Lee, and Corey C. Harwell
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Neurons ,cortical circuits ,1.1 Normal biological development and functioning ,Neurogenesis ,Medical Physiology ,astrocytes ,Neurosciences ,Sonic hedgehog ,General Biochemistry, Genetics and Molecular Biology ,Brain Disorders ,Underpinning research ,synapse formation ,Astrocytes ,Lrig1 ,Neurological ,Synapses ,Sparc ,Hedgehog Proteins ,neuron-glia interaction ,Biochemistry and Cell Biology - Abstract
Neuron-glia interactions play a critical role in the regulation of synapse formation and circuit assembly. Here we demonstrate that canonical Sonic hedgehog (Shh) pathway signaling in cortical astrocytes acts to coordinate layer-specific synaptic connectivity. We show that the Shh receptor Ptch1 is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of genes involved in regulating synaptic development and layer-enriched astrocyte molecular identity. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses; conversely, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Furthermore, Shh-dependent genes Lrig1 and Sparc distinctively contribute to astrocyte morphology and synapse formation. Together, these results suggest that Shh secreted from deep-layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.
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- 2021
19. Functional architecture of neural circuits for leg proprioception in Drosophila
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Gwyneth M Card, Brandon Mark, Sweta Agrawal, Anne Sustar, Jasper S. Phelps, Barry J. Dickson, Akira Mamiya, Chenghao Chen, Wei-Chung Allen Lee, and John C. Tuthill
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Proprioception ,Vibration sensing ,Computer science ,Functional connectivity ,Feedback control ,Biological neural network ,Sensory system ,Neuroscience - Abstract
To effectively control their bodies, animals rely on feedback from proprioceptive mechanosensory neurons. In the Drosophila leg, different proprioceptor subtypes monitor joint position, movement direction, and vibration. Here, we investigate how these diverse sensory signals are integrated by central proprioceptive circuits. We find that signals for leg joint position and directional movement converge in second-order neurons, revealing pathways for local feedback control of leg posture. Distinct populations of second-order neurons integrate tibia vibration signals across pairs of legs, suggesting a role in detecting external substrate vibration. In each pathway, the flow of sensory information is dynamically gated and sculpted by inhibition. Overall, our results reveal parallel pathways for processing of internal and external mechanosensory signals, which we propose mediate feedback control of leg movement and vibration sensing, respectively. The existence of a functional connectivity map also provides a resource for interpreting connectomic reconstruction of neural circuits for leg proprioception.
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- 2021
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20. Vascular and perivascular cell profiling reveals the molecular and cellular bases of blood-brain barrier heterogeneity
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Wei-Chung Allen Lee, Urs H. Langen, Faheem Nagpurwala, Indumathi Prakash, Chenghua Gu, Sarah J. Pfau, Theodore M. Fisher, Zhuhao Wu, and Ricardo A. Lozoya
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medicine.anatomical_structure ,Cortex (anatomy) ,Median eminence ,Central nervous system ,Cell ,medicine ,Biological neural network ,Extracellular ,Biology ,Blood–brain barrier ,Neuroscience ,Function (biology) - Abstract
SUMMARYThe blood-brain barrier (BBB) is critical for protecting the brain and maintaining neuronal homeostasis. Although the BBB is a unique feature of the central nervous system (CNS) vasculature, not all brain regions have the same degree of impermeability. Differences in BBB permeability are important for controlling the local extracellular environment of specific brain regions to regulate the function and plasticity of particular neural circuits. However, how BBB heterogeneity occurs is poorly understood. Here, we demonstrate how regional specialization of the BBB is achieved. With unbiased cell profiling in small, defined brain regions, we compare the median eminence, which has a naturally leaky BBB, with the cortex, which has an impermeable BBB. We identify hundreds of molecular differences in endothelial cells (ECs) and demonstrate the existence of differences in perivascular astrocytes and pericytes in these regions, finding 3 previously unknown subtypes of astrocytes and several key differences in pericytes. By serial electron microscopy reconstruction and a novel, aqueous-based tissue clearing imaging method, we further reveal previously unknown anatomical specializations of these perivascular cells and their unique physical interactions with neighboring ECs. Finally, we identify ligand-receptor pairs between ECs and perivascular cells that may regulate regional BBB integrity in ECs. Using a bioinformatic approach we identified 26 and 26 ligand-receptor pairs underlying EC-pericyte and EC-astrocyte interactions, respectively. Our results demonstrate that differences in ECs, together with region-specific physical and molecular interactions with local perivascular cells, contribute to BBB functional heterogeneity. These regional cell inventories serve as a platform for further investigation of the dynamic and heterogeneous nature of the BBB in other brain regions. Identification of local BBB specializations provides insight into the function of different brain regions and will permit the development of region-specific drug delivery in the CNS.
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- 2021
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21. Candelabrum cells are molecularly distinct, ubiquitous interneurons of the cerebellar cortex with specialized circuit properties
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Naeem Nadaf, Wade G. Regehr, Evan Z. Macosko, Stephanie Rudolph, Tomas Osorno, Wei-Chung Allen Lee, Tri Nguyen, and Kozareva
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Interneuron ,Chemistry ,fungi ,Purkinje cell ,In situ hybridization ,Electrophysiology ,medicine.anatomical_structure ,nervous system ,Disinhibition ,Cerebellar cortex ,medicine ,GABAergic ,Mossy fiber (cerebellum) ,medicine.symptom ,Neuroscience - Abstract
To understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections, and function remain unknown. Here we clarify these properties using electrophysiology, snRNA sequencing, in situ hybridization, and serial electron microscopy. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct, and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells, and strongly inhibited by PCs. CCs in turn inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals all converge onto CCs to allow them to assume a unique role in controlling cerebellar output.
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- 2021
- Full Text
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22. Astrocyte-Neuron Crosstalk Through Hedgehog Signaling Mediates Cortical Circuit Assembly
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Olivia Mosto, Nicolás Gómez, Ya-Jun Xie, Wei-Chung Allen Lee, Minsu Kim, Claire Charpentier, Corey C. Harwell, Ingie Sorour, Diana A. Tran, Steve Vu, Michael Y. Tolstorukov, Bernardo L. Sabatini, Manal A. Adam, Aaron T. Kuan, Wengang Wang, Zachary T. Herbert, and Olubusola Olukoya
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animal structures ,biology ,Chemistry ,Hedgehog signaling pathway ,Crosstalk (biology) ,medicine.anatomical_structure ,PTCH1 ,embryonic structures ,medicine ,biology.protein ,Neuron ,Sonic hedgehog ,Receptor ,Neuroscience ,Function (biology) ,Astrocyte - Abstract
Neuron-glia interactions play a critical role in the regulation of synapse formation and neuron specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that canonical Sonic hedgehog (Shh) pathway signaling in cortical astrocytes acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that the Shh receptor Ptch1 is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of genes involved in regulating synaptic development and layer-specific astrocyte molecular identity. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, conversely, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Furthermore, we determined that Shh-dependent genes Lrig1 and Sparc distinctively contribute to astrocyte morphology and synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.
- Published
- 2021
- Full Text
- View/download PDF
23. Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly
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Minsu Kim, Zachary T. Herbert, Nicolás Gómez, Aaron T. Kuan, Diana A. Tran, Olivia Mosto, Wei-Chung Allen Lee, Corey C. Harwell, Claire Charpentier, Ya-Jun Xie, Olubusola Olukoya, Michael Y. Tolstorukov, Steve Vu, Ingie Sorour, Wengang Wang, Manal A. Adam, and Bernardo L. Sabatini
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animal structures ,biology ,Chemistry ,Cortical neurons ,Hedgehog signaling pathway ,Crosstalk (biology) ,medicine.anatomical_structure ,PTCH1 ,embryonic structures ,medicine ,biology.protein ,Neuron ,Sonic hedgehog ,Receptor ,Neuroscience ,Astrocyte - Abstract
SUMMARYNeuron-glia relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that the canonical Sonic hedgehog (Shh) pathway is active in cortical astrocytes, where it acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that Ptch1 is a Shh receptor that is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of layer-specific astrocyte genes involved in regulating synapse formation and function. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, moreover, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.
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- 2020
- Full Text
- View/download PDF
24. Reconstruction of motor control circuits in adultDrosophilausing automated transmission electron microscopy
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Anthony W. Azevedo, Brendan L. Shanney, Wei-Chung Allen Lee, Logan A. Thomas, David G. C. Hildebrand, Jasper T. Maniates-Selvin, Aaron T. Kuan, John C. Tuthill, Tri Nguyen, Jan Funke, Brett J. Graham, and Julia Buhmann
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0303 health sciences ,biology ,Computer science ,Motor control ,Sensory system ,Motor neuron ,biology.organism_classification ,Synapse ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Transmission (telecommunications) ,Ventral nerve cord ,medicine ,Biological neural network ,Instrumentation (computer programming) ,Drosophila melanogaster ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
SUMMARYMany animals use coordinated limb movements to interact with and navigate through the environment. To investigate circuit mechanisms underlying locomotor behavior, we used serial-section electron microscopy (EM) to map synaptic connectivity within a neuronal network that controls limb movements. We present a synapse-resolution EM dataset containing the ventral nerve cord (VNC) of an adult femaleDrosophila melanogaster. To generate this dataset, we developed GridTape, a technology that combines automated serial-section collection with automated high-throughput transmission EM. Using this dataset, we reconstructed 507 motor neurons, including all those that control the legs and wings. We show that a specific class of leg sensory neurons directly synapse onto the largest-caliber motor neuron axons on both sides of the body, representing a unique feedback pathway for fast limb control. We provide open access to the dataset and reconstructions registered to a standard atlas to permit matching of cells between EM and light microscopy data. We also provide GridTape instrumentation designs and software to make large-scale EM data acquisition more accessible and affordable to the scientific community.
- Published
- 2020
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25. Functional architecture of neural circuits for leg proprioception in Drosophila
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Brandon Mark, Sweta Agrawal, Anne Sustar, Gwyneth M Card, Chenghao Chen, Akira Mamiya, Jasper S. Phelps, Wei-Chung Allen Lee, John C. Tuthill, and Barry J. Dickson
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Proprioception ,Sensory Receptor Cells ,Feedback control ,Functional connectivity ,Movement ,Motor control ,Sensory system ,Optogenetics ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Calcium imaging ,Biological neural network ,Animals ,Drosophila ,General Agricultural and Biological Sciences ,Neuroscience - Abstract
SUMMARY To effectively control their bodies, animals rely on feedback from proprioceptive mechanosensory neurons. In the Drosophila leg, different proprioceptor subtypes monitor joint position, movement direction, and vibration. Here, we investigate how these diverse sensory signals are integrated by central proprioceptive circuits. We find that signals for leg joint position and directional movement converge in second-order neurons, revealing pathways for local feedback control of leg posture. Distinct populations of second-order neurons integrate tibia vibration signals across pairs of legs, suggesting a role in detecting external substrate vibration. In each pathway, the flow of sensory information is dynamically gated and sculpted by inhibition. Overall, our results reveal parallel pathways for processing of internal and external mechanosensory signals, which we propose mediate feedback control of leg movement and vibration sensing, respectively. The existence of a functional connectivity map also provides a resource for interpreting connectomic reconstruction of neural circuits for leg proprioception., In brief To understand how diverse proprioceptive signals from the Drosophila leg are integrated by downstream circuits, Chen et al. use optogenetics and calcium imaging to map functional connectivity between sensory and central neurons. This work identifies parallel neural pathways for processing leg vibration vs. joint position and movement., Graphical abstract
- Published
- 2021
26. Whole-brain serial-section electron microscopy in larval zebrafish
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George S. Plummer, Isaac H. Bianco, Andrew Champion, Arthur W. Wetzel, David G. C. Hildebrand, Joshua T. Vogelstein, Marcelo Cicconet, Russel Torres, Alexander F. Schier, Owen Randlett, Randal Burns, Jeff W. Lichtman, Wei-Chung Allen Lee, Won-Ki Jeong, Stephan Saalfeld, Alexander D. Baden, Jungmin Moon, Florian Engert, Tran Minh Quan, Ruben Portugues, Woohyuk Choi, Kunal Lillaney, and Brett J. Graham
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0301 basic medicine ,Danio ,Datasets as Topic ,Nanotechnology ,Serial section ,Article ,Entire brain ,law.invention ,03 medical and health sciences ,Atlases as Topic ,Cellular neuroscience ,law ,Microscopy ,Zebrafish larvae ,medicine ,Fluorescence microscope ,Biological neural network ,Animals ,Anatomy, Artistic ,Zebrafish ,Sample handling ,Multidisciplinary ,biology ,Resolution (electron density) ,Brain ,biology.organism_classification ,Axons ,Microscopy, Electron ,Microscopy, Fluorescence, Multiphoton ,030104 developmental biology ,Visual cortex ,medicine.anatomical_structure ,Open Access Publishing ,Larva ,Ultrastructure ,Neuron ,Electron microscope ,Neuroscience - Abstract
Investigating the dense meshwork of wires and synapses that form neuronal circuits is possible with the high resolution of serial-section electron microscopy (ssEM)1. However, the imaging scale required to comprehensively reconstruct axons and dendrites is more than 10 orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons2—some of which span nearly the entire brain. The difficulties in generating and handling data for relatively large volumes at nanoscale resolution has thus restricted all studies in vertebrates to neuron fragments, thereby hindering investigations of complete circuits. These efforts were transformed by recent advances in computing, sample handling, and imaging techniques1, but examining entire brains at high resolution remains a challenge. Here we present ssEM data for a complete 5.5 days post-fertilisation larval zebrafish brain. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management. The resulting dataset can be analysed to reconstruct neuronal processes, allowing us to, for example, survey all the myelinated axons (the projectome). Further, our reconstructions enabled us to investigate the precise projections of neurons and their contralateral counterparts. In particular, we observed that myelinated axons of reticulospinal and lateral line afferent neurons exhibit remarkable bilateral symmetry. Additionally, we found that fasciculated reticulospinal axons maintain the same neighbour relations throughout the extent of their projections. Furthermore, we use the dataset to set the stage for whole-brain comparisons of structure and function by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. We provide the complete dataset and reconstructions as an open-access resource for neurobiologists and others interested in the ultrastructure of the larval zebrafish.
- Published
- 2017
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27. Automatic Detection of Synaptic Partners in a Whole-Brain Drosophila EM Dataset
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Stephan Saalfeld, Philipp Schlegel, Rachel Wilson, Wei-Chung Allen Lee, Julia Buhmann, Larissa Heinrich, Stephan Gerhard, Tri Nguyen, Davi D. Bock, Srinivas C. Turaga, Jan Funke, Matthew Cook, Arlo Sheridan, Gregory S.X.E. Jefferis, and Renate Krause
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0303 health sciences ,business.industry ,Computer science ,Pattern recognition ,Convolutional neural network ,030218 nuclear medicine & medical imaging ,Synapse ,03 medical and health sciences ,Identification (information) ,0302 clinical medicine ,medicine.anatomical_structure ,Biological neural network ,medicine ,Artificial intelligence ,Neuron ,business ,030304 developmental biology - Abstract
The study of neural circuits requires the reconstruction of neurons and the identification of synaptic connections between them. To scale the reconstruction to the size of whole-brain datasets, semi-automatic methods are needed to solve those tasks. Here, we present an automatic method for synaptic partner identification in insect brains, which uses convolutional neural networks to identify post-synaptic sites and their pre-synaptic partners. The networks can be trained from human generated point annotations alone and require only simple post-processing to obtain final predictions. We used our method to extract 244 million putative synaptic partners in the fifty-teravoxel full adult fly brain (FAFB) electron microscopy (EM) dataset and evaluated its accuracy on 146,643 synapses from 702 neurons with a total cable length of 312 mm in four different brain regions. The predicted synaptic connections can be used together with a neuron segmentation to infer a connectivity graph with high accuracy: between 92% and 96% of edges linking connected neurons are correctly classified as weakly connected (less than five synapses) and strongly connected (at least five synapses). Our synaptic partner predictions for the FAFB dataset are publicly available, together with a query library allowing automatic retrieval of up- and downstream neurons.
- Published
- 2019
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28. Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy
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Jan Funke, Logan A. Thomas, Tri Nguyen, Wei-Chung Allen Lee, Jasper S. Phelps, Anne Sustar, David G. C. Hildebrand, Brett J. Graham, John C. Tuthill, Julia Buhmann, Brendan L. Shanny, Aaron T. Kuan, Mingguan Liu, Anthony W. Azevedo, and Sweta Agrawal
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Connectomics ,Aging ,Sensory Receptor Cells ,Sensory system ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Automation ,0302 clinical medicine ,Software ,Microscopy, Electron, Transmission ,Connectome ,Animals ,Computer vision ,Instrumentation (computer programming) ,Peripheral Nerves ,030304 developmental biology ,Electronic circuit ,Motor Neurons ,0303 health sciences ,business.industry ,Motor control ,Extremities ,Drosophila melanogaster ,Transmission (telecommunications) ,Ventral nerve cord ,Synapses ,Artificial intelligence ,business ,030217 neurology & neurosurgery - Abstract
To investigate circuit mechanisms underlying locomotor behavior, we used serial-section electron microscopy (EM) to acquire a synapse-resolution dataset containing the ventral nerve cord (VNC) of an adult female Drosophila melanogaster. To generate this dataset, we developed GridTape, a technology that combines automated serial-section collection with automated high-throughput transmission EM. Using this dataset, we studied neuronal networks that control leg and wing movements by reconstructing all 507 motor neurons that control the limbs. We show that a specific class of leg sensory neurons synapses directly onto motor neurons with the largest-caliber axons on both sides of the body, representing a unique pathway for fast limb control. We provide open access to the dataset and reconstructions registered to a standard atlas to permit matching of cells between EM and light microscopy data. We also provide GridTape instrumentation designs and software to make large-scale EM more accessible and affordable to the scientific community.
- Published
- 2019
29. A Petascale Automated Imaging Pipeline for Mapping Neuronal Circuits with High-throughput Transmission Electron Microscopy
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Marie E. Scott, Marc Takeno, Daniel Kapner, Daniel J. Bumbarger, Christopher S. Own, R. Clay Reid, M.F. Murfitt, Adam Bleckert, Derric Williams, Brett J. Graham, Wenjing Yin, David Reid, Daniel Castelli, Wei-Chung Allen Lee, Nuno Macarico da Costa, Colin Farrell, Derrick Brittain, Jed Perkins, Jay Borseth, and Russel Torres
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Microscope ,business.industry ,Computer science ,Pipeline (computing) ,Resolution (electron density) ,law.invention ,Petascale computing ,Transmission (telecommunications) ,law ,Transmission electron microscopy ,Electron microscope ,business ,Throughput (business) ,Computer hardware - Abstract
Serial-section electron microscopy is the method of choice for studying cellular structure and network connectivity in the brain. We have built a pipeline of parallel imaging using transmission electron automated microscopes (piTEAM) that scales this technology and enables the acquisition of petascale datasets containing local cortical microcircuits. The distributed platform is composed of multiple transmission electron microscopes that image, in parallel, different sections from the same block of tissue, all under control of a custom acquisition software (pyTEM) that implements 24/7 continuous autonomous imaging. The suitability of this architecture for large scale electron microscopy imaging was demonstrated by acquiring a volume of more than 1 mm3 of mouse neocortex spanning four different visual areas. Over 26,500 ultrathin tissue sections were imaged, yielding a dataset of more than 2 petabytes. Our current burst imaging rate is 500 Mpixel/s (image capture only) per microscope and net imaging rate is 100 Mpixel/s (including stage movement, image capture, quality control, and post processing). This brings the combined burst acquisition rate of the pipeline to 3 Gpixel/s and the net rate to 600 Mpixel/s with six microscopes running acquisition in parallel, which allowed imaging a cubic millimeter of mouse visual cortex at synaptic resolution in less than 6 months.
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- 2019
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30. Removing Imaging Artifacts in Electron Microscopy using an Asymmetrically Cyclic Adversarial Network without Paired Training Data
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Won-Ki Jeong, Tran Minh Quan, Kanggeun Lee, David G. C. Hildebrand, Wei-Chung Allen Lee, Logan A. Thomas, and Aaron T. Kuan
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0303 health sciences ,Training set ,Matching (graph theory) ,Noise measurement ,Computer science ,business.industry ,Noise reduction ,Deep learning ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Pattern recognition ,030218 nuclear medicine & medical imaging ,Image (mathematics) ,03 medical and health sciences ,Noise ,0302 clinical medicine ,Computer Science::Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Image resolution ,030304 developmental biology - Abstract
We propose an asymmetrically cyclic adversarial network that performs denoising tasks to improve electron microscopy (EM) image analysis. Deep learning-based denoising methods have typically been trained either with matching pairs of noise-free and noise-corrupted images or by leveraging prior knowledge of noise distributions. Neither of these options is feasible in high-throughput EM imaging pipelines. Our proposed denoising method employs independently acquired noise-free, noise pattern, and noise-corrupted images to automatically learn the underlying noise model and generate denoised outputs. This method is based on three-way cyclic constraints with adversarial training of a deep network to improve the quality of acquired images without paired training data. Its utility is demonstrated for cases where imaging substrates add noise and where acquisition conditions contribute noise. We show that our method, which builds on the concept of CycleGAN, outperforms the current state-of-the-art denoising approaches Noise2Noise and Noise2Void, as well as other learning-based techniques.
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- 2019
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31. High-throughput transmission electron microscopy with automated serial sectioning
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Wei-Chung Allen Lee, David G. C. Hildebrand, Logan A. Thomas, Jasper T. Maniates-Selvin, Aaron T. Kuan, Brendan L. Shanny, and Brett J. Graham
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0303 health sciences ,business.industry ,Computer science ,Pipeline (computing) ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,03 medical and health sciences ,0302 clinical medicine ,Transmission electron microscopy ,Focus (optics) ,business ,Throughput (business) ,030217 neurology & neurosurgery ,Computer hardware ,030304 developmental biology - Abstract
Transmission electron microscopy (TEM) is an essential tool for studying cells and molecules. We present a tape-based, reel-to-reel pipeline that combines automated serial sectioning with automated high-throughput TEM imaging. This acquisition platform provides nanometer-resolution imaging at fast rates for a fraction of the cost of alternative approaches. We demonstrate the utility of this imaging platform for generating datasets of biological tissues with a focus on examining brain circuits.
- Published
- 2019
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32. Dense neuronal reconstruction through X-ray holographic nano-tomography
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Logan A. Thomas, Jasper T. Maniates-Selvin, Alexandra Pacureanu, Wei-Chung Allen Lee, Chiao-Lin Chen, Aaron T. Kuan, and Peter Cloetens
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Nervous system ,0303 health sciences ,Materials science ,Nervous tissue ,Resolution (electron density) ,Holography ,Convolutional neural network ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,law ,Microscopy ,medicine ,Tomography ,Electron microscope ,030217 neurology & neurosurgery ,030304 developmental biology ,Biomedical engineering - Abstract
Elucidating the structure of neuronal networks provides a foundation for understanding how the nervous system processes information to generate behavior. Despite technological breakthroughs in visible light and electron microscopy, imaging dense nanometer-scale neuronal structures over millimeter-scale tissue volumes remains a challenge. Here, we demonstrate that X-ray holographic nano-tomography is capable of imaging large tissue volumes with sufficient resolution to disentangle dense neuronal circuitry in Drosophila melanogaster and mammalian central and peripheral nervous tissue. Furthermore, we show that automatic segmentation using convolutional neural networks enables rapid extraction of neuronal morphologies from these volumetric datasets. The technique we present allows rapid data collection and analysis of multiple specimens, and can be used correlatively with light microscopy and electron microscopy on the same samples. Thus, X-ray holographic nano-tomography provides a new avenue for discoveries in neuroscience and life sciences in general.
- Published
- 2019
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33. Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism
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Linda C. Burkly, Beth Stevens, Wei-Chung Allen Lee, Lucas Cheadle, Samuel Rivera, Jasper S. Phelps, Michael E. Greenberg, and Katelin A. Ennis
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0301 basic medicine ,Dendritic spine ,Thalamus ,Mice, Transgenic ,Sensory system ,Biology ,Article ,Receptors, Tumor Necrosis Factor ,Synapse ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Microscopy, Electron, Transmission ,medicine ,Biological neural network ,Animals ,Visual Pathways ,Postnatal brain ,Neurons ,Retina ,Neuronal Plasticity ,Microglia ,General Neuroscience ,Cytokine TWEAK ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,TWEAK Receptor ,Tumor Necrosis Factors ,Synapses ,Neuroscience ,Photic Stimulation ,030217 neurology & neurosurgery - Abstract
Sensory experience remodels neural circuits in the early postnatal brain through mechanisms that remain to be elucidated. Applying a new method of ultrastructural analysis to the retinogeniculate circuit, we find that visual experience alters the number and structure of synapses between the retina and the thalamus. These changes require the vision-dependent transcription of the receptor Fn14 in thalamic relay neurons and the induction of its ligand TWEAK in microglia. Fn14 functions to increase the number of bulbous spine-associated synapses at retinogeniculate connections likely contributing to the strengthening of the circuit that occurs in response to visual experience. However, at retinogeniculate connections nearby TWEAK-expressing microglia, TWEAK signals via Fn14 to restrict the number of bulbous spines on relay neurons, leading to the elimination of a subset of connections. Thus, TWEAK and Fn14 represent an intercellular signaling axis through which microglia shape retinogeniculate connectivity in response to sensory experience.
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- 2020
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34. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
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Song Pang, Frank M. J. Jacobs, Michael E. Coulter, Raphael Gaudin, C. Shan Xu, Gerrald A Lodewijk, Ganeshwaran H. Mochida, Sarah Cianférani, Harald F. Hess, Wei-Chung Allen Lee, Christopher A. Walsh, Tomas Kirchhausen, Dilenny M. Gonzalez, Monica L. Calicchio, François Delalande, Edward Yang, Cristina M. Dorobantu, Richard S. Smith, Hart G.W. Lidov, David Haussler, Eric T. Wong, Vijay S. Ganesh, Maria K. Lehtinen, Elaine T. Lim, Thorsten M. Schlaeger, Molecular Neuroscience (SILS, FNWI), Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), McMaster Univ, Med Phys & Appl Radiat Sci Dept, Hamilton, ON L8S 4K1, Canada, Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Harvard Medical School [Boston] (HMS), Center for Biomolecular Science and Engineering, University of California [Santa Cruz] (UCSC), and University of California-University of California
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0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Medical Physiology ,Vesicular Transport Proteins ,Aucun ,Mice ,0302 clinical medicine ,microcephaly ,Sonic hedgehog ,Pediatric ,biology ,neurodevelopment ,Chemistry ,Brain ,Cell biology ,Stem Cell Research - Nonembryonic - Non-Human ,Adult ,Endosome ,1.1 Normal biological development and functioning ,Pontocerebellar hypoplasia ,CHMP1A ,Sciences du Vivant [q-bio]/Médecine humaine et pathologie ,Article ,General Biochemistry, Genetics and Molecular Biology ,ESCRT ,multivesicular body ,03 medical and health sciences ,Extracellular Vesicles ,sonic hedgehog ,Rare Diseases ,Clinical Research ,Underpinning research ,medicine ,Animals ,Humans ,Secretion ,Hedgehog Proteins ,Progenitor ,Endosomal Sorting Complexes Required for Transport ,Infant, Newborn ,Neurosciences ,Infant ,medicine.disease ,Newborn ,Stem Cell Research ,Brain Disorders ,030104 developmental biology ,Choroid Plexus ,biology.protein ,NIH 3T3 Cells ,Congenital Structural Anomalies ,Biochemistry and Cell Biology ,030217 neurology & neurosurgery ,RAB18 ,Biogenesis - Abstract
SUMMARY Endosomal sorting complex required for transport (ESCRT) complex proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential for development and adult function. We recently showed human loss-of-function (LOF) mutations in ESCRT-III member CHMP1A cause autosomal recessive microcephaly with pontocerebellar hypoplasia, but its mechanism was unclear. Here, we show Chmp1a is required for progenitor proliferation in mouse cortex and cerebellum and progenitor maintenance in human cerebral organoids. In Chmp1a null mice, this defect is associated with impaired sonic hedgehog (Shh) secretion and intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs). Furthermore, we show CHMP1A is important for release of an EV subtype that contains AXL, RAB18, and TMED10 (ART) and SHH. Our findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain., Graphical Abstract, In Brief Extracellular vesicles (EVs) are essential for cell-to-cell communication in developing brain. Coulter et al. show that the human microcephaly gene CHMP1A is required for neuroprogenitor proliferation through regulation of vesicular secretion of the growth factor sonic hedgehog (SHH). CHMP1A specifically impairs SHH secretion on a distinctive EV subtype, ART-EV.
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- 2018
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35. Author response: Wiring variations that enable and constrain neural computation in a sensory microcircuit
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Wei-Chung Allen Lee, Rachel Wilson, and William F Tobin
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Models of neural computation ,business.industry ,Computer science ,Sensory system ,Artificial intelligence ,business - Published
- 2017
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36. Extended Plasticity of Visual Cortex in Dark-Reared Animals May Result from Prolonged Expression ofcpg15-Like Genes
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Elly Nedivi and Wei-Chung Allen Lee
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Retina ,genetic structures ,General Neuroscience ,Superior colliculus ,Biology ,Lateral geniculate nucleus ,Monocular deprivation ,medicine.anatomical_structure ,Visual cortex ,Neuroplasticity ,medicine ,Sensory deprivation ,Neuroscience ,Critical period - Abstract
cpg15 is an activity-regulated gene that encodes a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. These properties make it an attractive candidate for participating in plasticity of the mammalian visual system. Here we compare cpg15 expression during normal development of the rat visual system with that seen in response to dark rearing, monocular blockade of retinal action potentials, or monocular deprivation. Our results show that the onset of cpg15 expression in the visual cortex is coincident with eye opening, and it increases until the peak of the critical period at postnatal day 28 (P28). This early expression is independent of both retinal activity and visual experience. After P28, a component of cpg15 expression in the visual cortex, lateral geniculate nucleus (LGN), and superior colliculus (SC) develops a progressively stronger dependence on retinally driven action potentials. Dark rearing does not affect cpg15 mRNA expression in the LGN and SC at any age, but it does significantly affect its expression in the visual cortex from the peak of the critical period and into adulthood. In dark-reared rats, the peak level of cpg15 expression in the visual cortex at P28 is lower than in controls. Rather than showing the normal decline with maturation, these levels are maintained in dark-reared animals. We suggest that the prolonged plasticity in the visual cortex that is seen in dark-reared animals may result from failure to downregulate genes such as cpg15 that could promote structural remodeling and synaptic maturation.
- Published
- 2002
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37. Anatomy and function of an excitatory network in the visual cortex
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Vincent Bonin, Katie J. Glattfelder, Wei-Chung Allen Lee, R. Clay Reid, Michael Douglas Reed, Greg Hood, and Brett J. Graham
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0301 basic medicine ,Male ,Connectomics ,Sensory processing ,medicine.medical_treatment ,Sensory system ,Biology ,Visual system ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Biological neural network ,Animals ,Visual Pathways ,Visual Cortex ,Photons ,Multidisciplinary ,Pyramidal Cells ,Anatomy ,Dendrites ,Axons ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Visual cortex ,Cerebral cortex ,Synapses ,Excitatory postsynaptic potential ,Calcium ,030217 neurology & neurosurgery - Abstract
Circuits in the cerebral cortex consist of thousands of neurons connected by millions of synapses. A precise understanding of these local networks requires relating circuit activity with the underlying network structure. For pyramidal cells in superficial mouse visual cortex (V1), a consensus is emerging that neurons with similar visual response properties excite each other1–5, but the anatomical basis of this recurrent synaptic network is unknown. We combined physiological imaging and large-scale electron microscopy (EM) to study an excitatory network in V1. We found that layer 2/3 neurons organized into subnetworks defined by anatomical connectivity, with more connections within than between groups. More specifically, we found that pyramidal neurons with similar orientation selectivity preferentially formed synapses with each other, despite the fact that axons and dendrites of all orientation selectivities pass near (< 5 μm) each other with roughly equal probability. Therefore, we predict that mechanisms of functionally specific connectivity take place at the length scale of spines. Neurons with similar orientation tuning formed larger synapses, potentially enhancing the net effect of synaptic specificity. With the ability to study thousands of connections in a single circuit, functional connectomics is proving a powerful method to uncover the organizational logic of cortical networks.
- Published
- 2014
38. Reel-to-Reel Electron Microscopy: Latency-Free Continuous Imaging of Large Sample Volumes
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Wei-Chung Allen Lee, M.F. Murfitt, R. Clay Reid, Brett J. Graham, David G. C. Hildebrand, Derrick Brittain, Christopher S. Own, Lawrence S. Own, and Nuno Maçarico da Costa
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Optics ,Materials science ,business.industry ,law ,Reel-to-reel audio tape recording ,Electron microscope ,Latency (engineering) ,business ,Instrumentation ,law.invention ,Large sample - Published
- 2015
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39. Inhibitory dendrite dynamics as a general feature of the adult cortical microcircuit
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Wei-Chung Allen Lee, Jerry L. Chen, Walter C. Lin, Genevieve H. Flanders, and Elly Nedivi
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Male ,Dendritic spine ,Interneuron ,Green Fluorescent Proteins ,Models, Neurological ,Dendrite ,Biology ,Dendritic branch ,Article ,Functional Laterality ,Mice ,Interneurons ,Neuroplasticity ,medicine ,Animals ,Visual Pathways ,Visual Cortex ,Brain Mapping ,Neocortex ,Neuronal Plasticity ,General Neuroscience ,Neural Inhibition ,Dendrites ,Mice, Inbred C57BL ,Visual cortex ,medicine.anatomical_structure ,Cortical map ,nervous system ,Nonlinear Dynamics ,Nerve Net ,Neuroscience ,Photic Stimulation - Abstract
The mammalian neocortex is functionally subdivided into architectonically distinct regions that process various types of information based on their source of afferent input. Yet, the modularity of neocortical organization in terms of cell type and intrinsic circuitry allows afferent drive to continuously reassign cortical map space. New aspects of cortical map plasticity include dynamic turnover of dendritic spines on pyramidal neurons and remodeling of interneuron dendritic arbors. While spine remodeling occurs in multiple cortical regions, it is not yet known whether interneuron dendrite remodeling is common across primary sensory and higher-level cortices. It is also unknown whether, like pyramidal dendrites, inhibitory dendrites respect functional domain boundaries. Given the importance of the inhibitory circuitry to adult cortical plasticity and the reorganization of cortical maps, we sought to address these questions by using two-photon microscopy to monitor interneuron dendritic arbors ofthy1-GFP-S transgenic mice expressing GFP in neurons sparsely distributed across the superficial layers of the neocortex. We find that interneuron dendritic branch tip remodeling is a general feature of the adult cortical microcircuit, and that remodeling rates are similar across primary sensory regions of different modalities, but may differ in magnitude between primary sensory versus higher cortical areas. We also show that branch tip remodeling occurs in bursts and respects functional domain boundaries.
- Published
- 2011
40. Specificity and randomness: structure-function relationships in neural circuits
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R. Clay Reid and Wei-Chung Allen Lee
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Cerebral Cortex ,Neurons ,Artificial neural network ,Nerve net ,General Neuroscience ,Information processing ,Wiring diagram ,Retina ,Article ,Sensory Physiology ,Functional imaging ,medicine.anatomical_structure ,Cerebral cortex ,Neural Pathways ,Synapses ,medicine ,Biological neural network ,Animals ,Humans ,Neural Networks, Computer ,Nerve Net ,Psychology ,Neuroscience - Abstract
A fundamental but unsolved problem in neuroscience is how connections between neurons might underlie information processing in central circuits. Building wiring diagrams of neural networks may accelerate our understanding of how they compute. But even if we had wiring diagrams, it is critical to know what neurons in a circuit are doing: their physiology. In both the retina and cerebral cortex, a great deal is known about topographic specificity, such as lamination, and cell-type specificity of connections. Little, however, is known about connections as they relate to function. Here, we review how advances in functional imaging and electron microscopy have recently allowed the examination of relationships between sensory physiology and synaptic connections in cortical and retinal circuits.
- Published
- 2011
41. Network anatomy and in vivo physiology of visual cortical neurons
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Hyon Suk Kim, Arthur W. Wetzel, R. Clay Reid, Edward R. Soucy, Aaron M. Kerlin, Davi D. Bock, Wei-Chung Allen Lee, Mark L. Andermann, Sergey Yurgenson, and Greg Hood
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Male ,Interneuron ,Nerve net ,Neural Inhibition ,Physiology ,Stimulus (physiology) ,Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Calcium imaging ,Microscopy, Electron, Transmission ,Interneurons ,medicine ,Animals ,Calcium Signaling ,030304 developmental biology ,Visual Cortex ,Neurons ,0303 health sciences ,Multidisciplinary ,Pyramidal Cells ,Anatomy ,Microtomy ,Visual cortex ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Cerebral cortex ,Synapses ,Neuron ,Nerve Net ,030217 neurology & neurosurgery - Abstract
In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property—the preferred stimulus orientation—of a group of neurons in the mouse primary visual cortex. We then used large-scale electron microscopy (EM) of serial thin sections to trace a portion of these neurons’ local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.
- Published
- 2010
42. Multifocal multiphoton microscopy based on multianode photomultiplier tubes
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Peter T. C. So, Karsten Bahlmann, Sergio Fantini, Wei-Chung Allen Lee, Elly Nedivi, Ki Hean Kim, Timothy Ragan, Christof Buehler, and Erica L. Heffer
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Point spread function ,Physics ,Photomultiplier ,Photon ,business.industry ,Mean free path ,Scattering ,Resolution (electron density) ,Atomic and Molecular Physics, and Optics ,Article ,Multifocal multiphoton microscopy ,Optics ,Two-photon excitation microscopy ,business - Abstract
Multifocal multiphoton microscopy (MMM) enhances imaging speed by parallelization. It is not well understood why the imaging depth of MMM is significantly shorter than conventional single-focus multiphoton microscopy (SMM). In this report, we show that the need for spatially resolved detectors in MMM results in a system that is more sensitive to the scattering of emission photons with reduced imaging depth. For imaging depths down to twice the scattering mean free path length of emission photons (2xl (s) (em)), the emission point spread function (PSF(em)) is found to consist of a narrow, diffraction limited distribution from ballistic emission photons and a broad, relatively low amplitude distribution from scattered photons. Since the scattered photon distribution is approximately 100 times wider than that of the unscattered photons at 2xl (s) (em), image contrast and depth are degraded without compromising resolution. To overcome the imaging depth limitation of MMM, we present a new design that replaces CCD cameras with multi-anode photomultiplier tubes (MAPMTs) allowing more efficient collection of scattered emission photons. We demonstrate that MAPMT-based MMM has imaging depth comparable to SMM with equivalent sensitivity by imaging tissue phantoms, ex vivo human skin specimens based on endogenous fluorophores, and green fluorescent protein (GFP) expressing neurons in mouse brain slices.
- Published
- 2009
43. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window
- Author
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Tara Keck, David K. Chow, Karel Svoboda, Mark Hübener, Graham Knott, JA Chuckowree, Thomas D. Mrsic-Flogel, Anthony Holtmaat, Tobias Bonhoeffer, Vincenzo De Paola, Joshua T. Trachtenberg, Linda Wilbrecht, Wei-Chung Allen Lee, Elly Nedivi, Ricardo Mostany, Carlos Portera-Cailliau, and Sonja B. Hofer
- Subjects
Bone flap ,Skull/surgery ,Craniotomy/methods ,Neocortex ,Biology ,Luminescent Proteins/analysis ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Article ,Mice ,In vivo ,Neuroplasticity ,Microscopy ,medicine ,Animals ,High resolution imaging ,Neurons ,Neuronal Plasticity ,Skull ,ddc:616.8 ,Electrophysiology ,Luminescent Proteins ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Neocortex/cytology/physiology ,Neurons/cytology/metabolism ,Craniotomy ,Biomedical engineering ,Cranial window - Abstract
To understand the cellular and circuit mechanisms of experience-dependent plasticity, neurons and their synapses need to be studied in the intact brain over extended periods of time. Two-photon excitation laser scanning microscopy (2PLSM), together with expression of fluorescent proteins, enables high-resolution imaging of neuronal structure in vivo. In this protocol we describe a chronic cranial window to obtain optical access to the mouse cerebral cortex for long-term imaging. A small bone flap is replaced with a coverglass, which is permanently sealed in place with dental acrylic, providing a clear imaging window with a large field of view (approximately 0.8-12 mm(2)). The surgical procedure can be completed within approximately 1 h. The preparation allows imaging over time periods of months with arbitrary imaging intervals. The large size of the imaging window facilitates imaging of ongoing structural plasticity of small neuronal structures in mice, with low densities of labeled neurons. The entire dendritic and axonal arbor of individual neurons can be reconstructed.
- Published
- 2009
44. A dynamic zone defines interneuron remodeling in the adult neocortex
- Author
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Jerry L. Chen, Wei-Chung Allen Lee, Peter T. C. So, Elly Nedivi, Hayden Huang, Jennifer H. Leslie, and Yael Amitai
- Subjects
Multidisciplinary ,Neocortex ,Neuronal Plasticity ,Interneuron ,Dendrite ,Mice, Transgenic ,Anatomy ,Biology ,Plasticity ,Biological Sciences ,gamma-Aminobutyric acid ,Mice ,medicine.anatomical_structure ,nervous system ,Interneurons ,Neuroplasticity ,Structural plasticity ,medicine ,GABAergic ,Animals ,Neuroscience ,gamma-Aminobutyric Acid ,medicine.drug - Abstract
The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a “dynamic zone” corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae.
- Published
- 2008
45. Correction: Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex
- Author
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Peter T. C. So, Guoping Feng, Joshua R. Sanes, Hayden Huang, Wei-Chung Allen Lee, Elly Nedivi, and Emery N. Brown
- Subjects
General Immunology and Microbiology ,QH301-705.5 ,General Neuroscience ,digestive, oral, and skin physiology ,Correction ,food and beverages ,Biology ,Mus (Mouse) ,General Biochemistry, Genetics and Molecular Biology ,medicine.anatomical_structure ,Visual cortex ,nervous system ,Cerebral cortex ,medicine ,GABAergic ,Biology (General) ,General Agricultural and Biological Sciences ,Neuroscience ,Preclinical imaging - Abstract
Chronic in vivo imaging of fluorescent-labeled neurons in adult mice reveals extension and retraction of dendrites in GABAergic non-pyramidal interneurons of the cerebral cortex.
- Published
- 2006
46. Dynamic Remodelling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex
- Author
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Elly Nedivi, Wei-Chung Allen Lee, Joshua R. Sanes, Emery N. Brown, Peter T. C. So, Guoping Feng, and Hayden Huang
- Subjects
Aging ,Time Factors ,QH301-705.5 ,Period (gene) ,Biology ,Plasticity ,General Biochemistry, Genetics and Molecular Biology ,gamma-Aminobutyric acid ,Mice ,Cortex (anatomy) ,Neuroplasticity ,medicine ,Animals ,Biology (General) ,gamma-Aminobutyric Acid ,Visual Cortex ,General Immunology and Microbiology ,General Neuroscience ,Anatomy ,Dendrites ,Mus (Mouse) ,Rats ,Visual cortex ,medicine.anatomical_structure ,nervous system ,Gene Expression Regulation ,Cerebral cortex ,Synopsis ,GABAergic ,General Agricultural and Biological Sciences ,Neuroscience ,medicine.drug ,Research Article - Abstract
Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. To examine the extent of neuronal remodeling that occurs in the brain on a day-to-day basis, we used a multiphoton-based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here we show the first unambiguous evidence (to our knowledge) of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA-positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and they suggest that circuit rearrangement in the adult cortex is restricted by cell type–specific rules., Chronic in vivo imaging of fluorescent-labeled neurons in adult mice reveals extension and retraction of dendrites in GABAergic non-pyramidal interneurons of the cerebral cortex.
- Published
- 2005
47. Regulation of cpg15 by signaling pathways that mediate synaptic plasticity
- Author
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Elly Nedivi, Wei-Chung Allen Lee, and Tadahiro Fujino
- Subjects
Transcriptional Activation ,Calcium Channels, L-Type ,MAP Kinase Signaling System ,Presynaptic Terminals ,Nonsynaptic plasticity ,Mice, Transgenic ,Nerve Tissue Proteins ,CREB ,GPI-Linked Proteins ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Article ,Cellular and Molecular Neuroscience ,Mice ,Cyclic AMP ,Animals ,Calcium Signaling ,Cyclic AMP Response Element-Binding Protein ,Promoter Regions, Genetic ,Molecular Biology ,Neuronal memory allocation ,Genes, Immediate-Early ,Cells, Cultured ,Calcium signaling ,Regulation of gene expression ,Synaptic scaling ,Binding Sites ,Neuronal Plasticity ,biology ,Membrane Proteins ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Cell biology ,Mice, Inbred C57BL ,Synaptic fatigue ,Calcium-Calmodulin-Dependent Protein Kinase Type 1 ,Gene Expression Regulation ,Synaptic plasticity ,Calcium-Calmodulin-Dependent Protein Kinases ,biology.protein ,Signal Transduction - Abstract
Transcriptional activation is a key link between neuronal activity and long-term synaptic plasticity. Little is known about genes responding to this activation whose products directly effect functional and structural changes at the synapse. cpg15 is an activity-regulated gene encoding a membrane-bound ligand that regulates dendritic and axonal arbor growth and synaptic maturation. We report that cpg15 is an immediate-early gene induced by Ca(2+) influx through NMDA receptors and L-type voltage-sensitive calcium channels. Activity-dependent cpg15 expression requires convergent activation of the CaM kinase and MAP kinase pathways. Although activation of PKA is not required for activity-dependent expression, cpg15 is induced by cAMP in active neurons. CREB binds the cpg15 promoter in vivo and partially regulates its activity-dependent expression. cpg15 is an effector gene that is a target for signal transduction pathways that mediate synaptic plasticity and thus may take part in an activity-regulated transcriptional program that directs long-term changes in synaptic connections.
- Published
- 2003
48. Extended plasticity of visual cortex in dark-reared animals may result from prolonged expression of cpg15-like genes
- Author
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Wei-Chung Allen, Lee and Elly, Nedivi
- Subjects
Drug Implants ,Neuronal Plasticity ,genetic structures ,Light ,Critical Period, Psychological ,Action Potentials ,Down-Regulation ,Gene Expression Regulation, Developmental ,Membrane Proteins ,Nerve Tissue Proteins ,Tetrodotoxin ,Darkness ,Eye ,Ligands ,Rats, Inbred WKY ,Retina ,Article ,Rats ,Animals ,RNA, Messenger ,Sensory Deprivation ,In Situ Hybridization ,Vision, Ocular ,Visual Cortex - Abstract
cpg15 is an activity-regulated gene that encodes a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. These properties make it an attractive candidate for participating in plasticity of the mammalian visual system. Here we compare cpg15 expression during normal development of the rat visual system with that seen in response to dark rearing, monocular blockade of retinal action potentials, or monocular deprivation. Our results show that the onset of cpg15 expression in the visual cortex is coincident with eye opening, and it increases until the peak of the critical period at postnatal day 28 (P28). This early expression is independent of both retinal activity and visual experience. After P28, a component of cpg15 expression in the visual cortex, lateral geniculate nucleus (LGN), and superior colliculus (SC) develops a progressively stronger dependence on retinally driven action potentials. Dark rearing does not affect cpg15 mRNA expression in the LGN and SC at any age, but it does significantly affect its expression in the visual cortex from the peak of the critical period and into adulthood. In dark-reared rats, the peak level of cpg15 expression in the visual cortex at P28 is lower than in controls. Rather than showing the normal decline with maturation, these levels are maintained in dark-reared animals. We suggest that the prolonged plasticity in the visual cortex that is seen in dark-reared animals may result from failure to downregulate genes such as cpg15 that could promote structural remodeling and synaptic maturation.
- Published
- 2002
49. Large-Scale Automated Histology in the Pursuit of Connectomes.
- Author
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Kleinfeld, David, Bharioke, Arjun, Blinder, Pablo, Bock, Davi D., Briggman, Kevin L., Chklovskii, Dmitri B., Denk, Winfried, Helmstaedter, Moritz, Kaufhold, John P., Wei-Chung Allen Lee, Meyer, Hanno S., Micheva, Kristina D., Oberlaender, Marcel, Prohaska, Steffen, Reid, R. Clay, Smith, Stephen J., Takemura, Shinya, Tsai, Philbert S., and Sakmann, Bert
- Subjects
HISTOLOGY ,NEUROPLASTICITY ,NEURAL circuitry ,BRAIN function localization ,DATA analysis ,VISUALIZATION ,NEURONS - Abstract
How does the brain compute? Answering this question necessitates neuronal connectomes, annotated graphs of aU synaptic connections within defined brain areas. Further, understanding the energetics of the brain's computations require vascular graphs. The a embly of a connectomc requires sensitive hardware tools to measure neuronal and neurovascular features in all three dimensions, as weU as software and machine learning for data analysis and visualization. We present the state of the art on the reconstruction of circuits and vasculature that link brain anatomy and function. Analysis at the scale of tens of nanometers yields connections between identified neurons, while analysis at the micrometer scale yields probabilistic rules of connection between neurons and exact vascular connectivity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
50. Inhibitory Dendrite Dynamics as a General Feature of the Adult Cortical Microcircuit.
- Author
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Chen, Jerry L., Flanders, Genevieve H., Wei-Chung, Allen Lee, Lin, Walter C., and Nedivi, Elly
- Subjects
INTERNEURONS ,DENDRITIC cells ,VISUAL cortex ,MEDICAL microscopy ,NEURAL circuitry ,LABORATORY mice - Abstract
The article discusses a study conducted on transgenic mice to analyze the role of interneuron dendritic branch tip remodeling in the adult cortical microcircuit. The study found that interneuron dendritic remodeling is an intrinsic feature of the neocortical microcircuit and it occurs in primary visual and somatosensory cortices and in higher-order visual cortex. As stated, two-photon microscopy technique was used to visualize dendritic branch tip dynamics in cortical interneurons.
- Published
- 2011
- Full Text
- View/download PDF
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