18 results on '"John C Tuthill"'
Search Results
2. A size principle for recruitment of Drosophila leg motor neurons
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John C. Tuthill, Anthony W. Azevedo, Evyn S. Dickinson, Richard S. Mann, Lalanti Venkatasubramanian, Pralaksha Gurung, Azevedo, Anthony W [0000-0001-8318-9678], Dickinson, Evyn S [0000-0001-7518-9512], Venkatasubramanian, Lalanti [0000-0002-9280-8335], Mann, Richard S [0000-0002-4749-2765], Tuthill, John C [0000-0002-5689-5806], and Apollo - University of Cambridge Repository
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0301 basic medicine ,muscle ,QH301-705.5 ,proprioception ,Science ,General Biochemistry, Genetics and Molecular Biology ,neuroscience ,03 medical and health sciences ,0302 clinical medicine ,Calcium imaging ,Motor system ,medicine ,motor control ,Animals ,Biology (General) ,motor neuron ,Drosophila ,Motor Neurons ,General Immunology and Microbiology ,biology ,Proprioception ,D. melanogaster ,Tibia ,Electromyography ,General Neuroscience ,Work (physics) ,Motor control ,General Medicine ,Motor neuron ,biology.organism_classification ,Biomechanical Phenomena ,Electrophysiology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Medicine ,Neuroscience ,030217 neurology & neurosurgery - Abstract
To move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. Here, we use in vivo calcium imaging, electrophysiology, and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia. We find that leg motor neurons exhibit a coordinated gradient of anatomical, physiological, and functional properties. Large, fast motor neurons control high force, ballistic movements while small, slow motor neurons control low force, postural movements. Intermediate neurons fall between these two extremes. This hierarchical organization resembles the size principle, first proposed as a mechanism for establishing recruitment order among vertebrate motor neurons. Recordings in behaving flies confirmed that motor neurons are typically recruited in order from slow to fast. However, we also find that fast, intermediate, and slow motor neurons receive distinct proprioceptive feedback signals, suggesting that the size principle is not the only mechanism that dictates motor neuron recruitment. Overall, this work reveals the functional organization of the fly leg motor system and establishes Drosophila as a tractable system for investigating neural mechanisms of limb motor control.
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- 2020
3. A Systematic Nomenclature for the Drosophila Ventral Nerve Cord
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Richard S. Mann, James W. Truman, Robert Court, Darren W. Williams, Wyatt Korff, John C. Tuthill, Michael H. Dickinson, David J. Merritt, Julie H. Simpson, Troy R. Shirangi, Jana Börner, Marta Costa, Gwyneth M Card, Shigehiro Namiki, David Shepherd, Andrew M. Seeds, Rod K. Murphey, J. Douglas Armstrong, and Carsten Duch
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0301 basic medicine ,Nervous system ,anatomy ,tectulum ,animal structures ,1.1 Normal biological development and functioning ,neuropil ,Sensory system ,hemilineage ,Article ,03 medical and health sciences ,0302 clinical medicine ,Terminology as Topic ,medicine ,Neuropil ,Psychology ,Animals ,Cell Lineage ,Invertebrate ,ontology ,Nomenclature ,Neurons ,Neurology & Neurosurgery ,biology ,General Neuroscience ,fungi ,Neurosciences ,Commissure ,motorneuron ,biology.organism_classification ,Neuromere ,tract ,Ganglia, Invertebrate ,030104 developmental biology ,medicine.anatomical_structure ,Drosophila melanogaster ,Ventral nerve cord ,Neurological ,Ganglia ,commissure ,insect ,Cognitive Sciences ,Nerve Net ,Neuroscience ,030217 neurology & neurosurgery ,neuromere - Abstract
Drosophila melanogaster is an established model for neuroscience research with relevance in biology and medicine. Until recently, research on the Drosophila brain was hindered by the lack of a complete and uniform nomenclature. Recognizing this, Ito et al. (2014) produced an authoritative nomenclature for the adult insect brain, using Drosophila as the reference. Here, we extend this nomenclature to the adult thoracic and abdominal neuromeres, the ventral nerve cord (VNC), to provide an anatomical description of this major component of the Drosophila nervous system. The VNC is the locus for the reception and integration of sensory information and involved in generating most of the locomotor actions that underlie fly behaviors. The aim is to create a nomenclature, definitions, and spatial boundaries for the Drosophila VNC that are consistent with other insects. The work establishes an anatomical framework that provides a powerful tool for analyzing the functional organization of the VNC.
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- 2020
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4. Microtubule Acetylation Is Required for Mechanosensation in Drosophila
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Richard Superfine, John C. Tuthill, Joshua C. Vaughan, Jill Wildonger, Jay Z. Parrish, Yun Peng, Jonathan B. Perr, Fei Wang, E. Timothy O'Brien, Claire R. Williams, Stephen L. Rogers, Yang Xiang, Connie Yan, Hyeon-Jin Kim, Megan E. Kern, Michael R. Falvo, and Brian V. Jenkins
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0301 basic medicine ,Stimulation ,Sensory system ,medicine.disease_cause ,Mechanotransduction, Cellular ,Microtubules ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,Transient Receptor Potential Channels ,Microtubule ,Acetyltransferases ,Peripheral Nervous System ,medicine ,Morphogenesis ,Animals ,Drosophila Proteins ,lcsh:QH301-705.5 ,Cells, Cultured ,Mutation ,Mechanosensation ,Chemistry ,Acetylation ,Dendrites ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Drosophila melanogaster ,lcsh:Biology (General) ,Peripheral nervous system ,Larva ,030217 neurology & neurosurgery - Abstract
Summary: At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, although prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but it is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation. : Yan et al. identify the major microtubule acetylase in Drosophila and show that the enzyme and microtubule acetylation broadly control mechanosensation, but not other sensory modalities. Acetylation is required for mechanosensation by the TRP channel NOMPC, and possibly other channels, by virtue of its effects on microtubule mechanical stability and/or dynamics. Keywords: Drosophila, mechanosensation, microtubule acetylation, TRP channel, somatosensory neuron
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- 2018
5. A leg to stand on: computational models of proprioception
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Chris J. Dallmann, Pierre Karashchuk, John C. Tuthill, and Bingni W. Brunton
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0301 basic medicine ,03 medical and health sciences ,Computational model ,030104 developmental biology ,0302 clinical medicine ,Proprioception ,Physiology ,Computer science ,Physiology (medical) ,Motor control ,Neuroscience ,Article ,030217 neurology & neurosurgery - Abstract
Dexterous motor control requires feedback from proprioceptors, internal mechanosensory neurons that sense the body’s position and movement. An outstanding question in neuroscience is how diverse proprioceptive feedback signals contribute to flexible motor control. Genetic tools now enable targeted recording and perturbation of proprioceptive neurons in behaving animals; however, these experiments can be challenging to interpret, due to the tight coupling of proprioception and motor control. Here, we argue that understanding the role of proprioceptive feedback in controlling behavior will be aided by the development of multiscale models of sensorimotor loops. We review current phenomenological and structural models for proprioceptor encoding and discuss how they may be integrated with existing models of posture, movement, and body state estimation.
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- 2021
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6. 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.
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- 2020
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7. 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.
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- 2019
8. A size principle for leg motor control in Drosophila
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John C. Tuthill, Anthony W. Azevedo, Evyn S. Dickinson, Pralaksha Gurung, Richard S. Mann, and Lalanti Venkatasubramanian
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0303 health sciences ,biology ,Motor control ,Optogenetics ,Motor neuron ,biology.organism_classification ,03 medical and health sciences ,Electrophysiology ,0302 clinical medicine ,medicine.anatomical_structure ,Calcium imaging ,nervous system ,Motor system ,medicine ,Drosophila melanogaster ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
SummaryTo move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. In many species, including vertebrates, the motor neurons innervating a given muscle fire in a specific order that is determined by a gradient of cellular size and electrical excitability. This hierarchy allows premotor circuits to recruit motor neurons of increasing force capacity in a task-dependent manner. However, it remains unclear whether such a size principle also applies to species with more compact motor systems, such as the fruit fly,Drosophila melanogaster, which has just 53 motor neurons per leg. Usingin vivocalcium imaging and electrophysiology, we found that genetically-identified motor neurons controlling flexion of the fly tibia exhibit a gradient of anatomical, physiological, and functional properties consistent with the size principle. Large, fast motor neurons control high force, ballistic movements while small, slow motor neurons control low force, postural movements. Intermediate neurons fall between these two extremes. In behaving flies, motor neurons are recruited in order from slow to fast. This hierarchical organization suggests that slow and fast motor neurons control distinct motor regimes. Indeed, we find that optogenetic manipulation of each motor neuron type has distinct effects on the behavior of walking flies.
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- 2019
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9. Parallel Transformation of Tactile Signals in Central Circuits of Drosophila
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John C. Tuthill and Rachel Wilson
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0301 basic medicine ,Optogenetics ,Biology ,Stimulus (physiology) ,Somatosensory system ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Neural Pathways ,medicine ,Animals ,Axon ,Electronic circuit ,Neurons ,Proprioception ,Biochemistry, Genetics and Molecular Biology(all) ,Extremities ,Anatomy ,Axons ,Mechanoreceptor ,body regions ,030104 developmental biology ,medicine.anatomical_structure ,Touch ,Drosophila ,Female ,Neuron ,Mechanoreceptors ,Neuroscience - Abstract
To distinguish between complex somatosensory stimuli, central circuits must combine signals from multiple peripheral mechanoreceptor types, as well as mechanoreceptors at different sites in the body. Here, we investigate the first stages of somatosensory integration in Drosophila using in vivo recordings from genetically labeled central neurons, in combination with mechanical and optogenetic stimulation of specific mechanoreceptor types. We identify three classes of central neurons that process touch: one compares touch signals on different parts of the same limb, one compares touch signals on right and left limbs, and the third compares touch and proprioceptive signals. Each class encodes distinct features of somatosensory stimuli. The axon of an individual touch receptor neuron can diverge to synapse onto all three classes, meaning that these computations occur in parallel, not hierarchically. Representing a stimulus as a set of parallel comparisons is a fast and efficient way to deliver somatosensory signals to motor circuits.
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- 2016
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10. Four to Foxtrot: How Visual Motion Is Computed in the Fly Brain
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John C. Tuthill and Bart G. Borghuis
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Neurons ,0301 basic medicine ,Sensory Receptor Cells ,Neuroscience(all) ,General Neuroscience ,Motion Perception ,Presynaptic Terminals ,Biology ,Visual motion ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,medicine ,Animals ,Calcium ,Neuron ,Motion perception ,Neuroscience ,Motion computation - Abstract
In this issue of Neuron, Serbe et al. (2016) use cell-type-specific genetic tools to record and manipulate all major inputs to directionally selective neurons in Drosophila. Their results localize the site of motion computation and reveal unexpected complexity of temporal tuning in the underlying neural circuit.
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- 2016
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11. Proprioception
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John C. Tuthill and Eiman Azim
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Movement ,Posture ,Humans ,General Agricultural and Biological Sciences ,Proprioception ,030217 neurology & neurosurgery ,General Biochemistry, Genetics and Molecular Biology - Abstract
Although familiar to each of us, the sensation of inhabiting a body is ineffable. Traditional senses like vision and hearing monitor the external environment, allowing humans to have shared sensory experiences. But proprioception, the sensation of body position and movement, is fundamentally personal and typically absent from conscious perception. Nonetheless, this 'sixth sense' remains critical to human experience, a fact that is most apparent when one considers those who have lost it. Take, for example, the case of Ian Waterman who, at the age of 19, suffered a rare autoimmune response to a flu infection that attacked the sensory neurons from his neck down. This infection deprived him of the sense of position, movement and touch in his body. With this loss of feedback came a complete inability to coordinate his movements. While he could compel his muscles to contract, he lost the ability to orchestrate these actions into purposeful behaviors, in essence leaving him immobile, unable to stand, walk, or use his body to interact with the world. Only after years of dedicated training was he able to re-learn to move his body entirely under visual control.
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- 2018
12. A Systematic Nomenclature for theDrosophilaVentral Nervous System
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David Shepherd, Richard S. Mann, David J. Merritt, Carsten Duch, Andrew M. Seeds, James W. Truman, Rod K. Murphey, John C. Tuthill, Shigehiro Namiki, Robert Court, Darren W. Williams, Troy R. Shirangi, Michael H. Dickinson, Jana Börner, Julie A. Simpson, James Douglas Armstrong, Gwyneth M Card, Marta Costa, and Wyatt Korff
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Nervous system ,0303 health sciences ,biology ,media_common.quotation_subject ,fungi ,Adult insect ,Anatomy ,Insect ,biology.organism_classification ,Neuromere ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Taxon ,medicine.anatomical_structure ,medicine ,Drosophila melanogaster ,Drosophila (subgenus) ,Neuroscience ,Nomenclature ,030217 neurology & neurosurgery ,030304 developmental biology ,media_common - Abstract
The fruit fly,Drosophila melanogaster, is an established and powerful model system for neuroscience research with wide relevance in biology and medicine. Until recently, research on theDrosophilabrain was hindered by the lack of a complete and uniform nomenclature. Recognising this problem, the Insect Brain Name Working Group produced an authoritative hierarchical nomenclature system for the adult insect brain, usingDrosophila melanogasteras the reference framework, with other taxa considered to ensure greater consistency and expandability (Ito et al., 2014). Here, we extend this nomenclature system to the sub-gnathal regions of the adultDrosophilanervous system, thus providing a systematic anatomical description of the ventral nervous system (VNS). This portion of the nervous system includes the thoracic and abdominal neuromeres that were not included in the original work and contains the motor circuits that play essential roles in most fly behaviours.
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- 2017
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13. Mechanosensation and adaptive motor control in insects
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John C. Tuthill and Rachel Wilson
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0301 basic medicine ,Insecta ,Mechanosensation ,Motor commands ,Sensation ,Motor control ,Sensory system ,Anatomy ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Stimulus modality ,Biological neural network ,Animals ,Cues ,General Agricultural and Biological Sciences ,Neuroscience ,Mechanoreceptors ,030217 neurology & neurosurgery ,Locomotion - Abstract
The ability of animals to flexibly navigate through complex environments depends on the integration of sensory information with motor commands. The sensory modality most tightly linked to motor control is mechanosensation. Adaptive motor control depends critically on an animal’s ability to respond to mechanical forces generated both within and outside the body. The compact neural circuits of insects provide appealing systems to investigate how mechanical cues guide locomotion in rugged environments. Here, we review our current understanding of mechanosensation in insects and its role in adaptive motor control. We first examine the detection and encoding of mechanical forces by primary mechanoreceptor neurons. We then discuss how central circuits integrate and transform mechanosensory information to guide locomotion. Because most studies in this field have been performed in locusts, cockroaches, crickets, and stick insects, the examples we cite here are drawn mainly from these ‘big insects’. However, we also pay particular attention to the tiny fruit fly, Drosophila, where new tools are creating new opportunities, particularly for understanding central circuits. Our aim is to show how studies of big insects have yielded fundamental insights relevant to mechanosensation in all animals, and also to point out how the Drosophila toolkit can contribute to future progress in understanding mechanosensory processing.
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- 2016
14. What's on the vibrissa abscissa?
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John C. Tuthill
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0301 basic medicine ,Communication ,Physiology ,business.industry ,Whiskers ,media_common.quotation_subject ,Abscissa ,Art ,Anatomy ,Aquatic Science ,03 medical and health sciences ,symbols.namesake ,030104 developmental biology ,Insect Science ,symbols ,Animal Science and Zoology ,business ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,media_common - Abstract
[Graphic][1] The face of a rat is peppered with stiff, conical hairs called vibrissae, more commonly known as whiskers. As nocturnal animals that live in dingy, cramped hovels, rats rely on tactile information from their whiskers to get through the night. Using just their whiskers, they can
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- 2016
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15. This is Cerebrospinal Tap
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John C. Tuthill
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0301 basic medicine ,Nervous system ,Physiology ,business.industry ,Anatomy ,Aquatic Science ,Ventricular system ,Spinal cord ,03 medical and health sciences ,030104 developmental biology ,Cerebrospinal fluid ,medicine.anatomical_structure ,Insect Science ,Anesthesia ,cardiovascular system ,Medicine ,Animal Science and Zoology ,business ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
[Graphic][1] Of all the fluids produced by the human body, the cerebrospinal fluid (CSF) may be the least offensive. A clear, unassuming liquid, CSF circulates throughout the ventricular system of the brain and the central canal of the spinal cord, cushioning the nervous system from injury
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- 2016
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16. The odds of rolling snake eyes
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John C. Tuthill
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0106 biological sciences ,0301 basic medicine ,genetic structures ,Physiology ,Color vision ,Anatomy ,Aquatic Science ,Biology ,010603 evolutionary biology ,01 natural sciences ,eye diseases ,03 medical and health sciences ,030104 developmental biology ,Snake eyes ,Insect Science ,Animal Science and Zoology ,sense organs ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
[Graphic][1] Most vertebrate retinas are composed of two types of photoreceptors: rods, for dim light vision, and cones, for color vision under brighter conditions. However, several interesting exceptions to this duplex organization are seen in the squamate reptiles, a scaly group that
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- 2016
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17. How crabs enjoy a hot meal
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John C. Tuthill
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0301 basic medicine ,Meal ,Communication ,biology ,Physiology ,business.industry ,Aquatic Science ,biology.organism_classification ,Crustacean ,Fishery ,03 medical and health sciences ,030104 developmental biology ,Insect Science ,Animal Science and Zoology ,Business ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
[Graphic][1] Crabs are renowned for their cranky demeanor, but when one considers the extreme conditions under which they must survive, it becomes easier to sympathize with these crotchety crustaceans. One hardship that crabs must endure is changing temperature: a daily swing of 20°C is not
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- 2016
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18. Dense neuronal reconstruction through X-ray holographic nano-tomography
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Jan Funke, John C. Tuthill, Peter Cloetens, Logan A. Thomas, Julie Han, Jasper S. Phelps, Anthony W. Azevedo, Wei-Chung Allen Lee, Alexandra Pacureanu, Chiao-Lin Chen, Aaron T. Kuan, and Tri Nguyen
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Male ,0301 basic medicine ,Nervous system ,Sensory Receptor Cells ,Holography ,Convolutional neural network ,Machine Learning ,Mice ,03 medical and health sciences ,Imaging, Three-Dimensional ,0302 clinical medicine ,Cellular neuroscience ,Microscopy ,Image Processing, Computer-Assisted ,medicine ,Biological neural network ,Animals ,Nanotechnology ,Muscle, Skeletal ,Tomography ,Cerebral Cortex ,Motor Neurons ,Neurons ,Physics ,Pyramidal Cells ,General Neuroscience ,Nervous tissue ,Resolution (electron density) ,Dendrites ,Axons ,Mice, Inbred C57BL ,Drosophila melanogaster ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Neural Networks, Computer ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Imaging neuronal networks provides a foundation for understanding the nervous system, but resolving dense nanometer-scale structures over large volumes remains challenging for light microscopy (LM) and electron microscopy (EM). Here we show that X-ray holographic nano-tomography (XNH) can image millimeter-scale volumes with sub-100-nm resolution, enabling reconstruction of dense wiring in Drosophila melanogaster and mouse nervous tissue. We performed correlative XNH and EM to reconstruct hundreds of cortical pyramidal cells and show that more superficial cells receive stronger synaptic inhibition on their apical dendrites. By combining multiple XNH scans, we imaged an adult Drosophila leg with sufficient resolution to comprehensively catalog mechanosensory neurons and trace individual motor axons from muscles to the central nervous system. To accelerate neuronal reconstructions, we trained a convolutional neural network to automatically segment neurons from XNH volumes. Thus, XNH bridges a key gap between LM and EM, providing a new avenue for neural circuit discovery. Kuan, Phelps, et al. used synchrotron X-ray imaging and deep learning to map dense neuronal wiring in fly and mouse tissue, enabling examination of individual cells and connectivity in circuits governing motor control and perceptual decision-making.
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