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  1. Article: Selective modification of ascending spinal outputs in acute and neuropathic pain states.

    Yarmolinsky, David A / Zeng, Xiangsunze / MacKinnon-Booth, Natalie / Greene, Caitlin / Kim, Chloe / Woolf, Clifford J

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Pain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain and alters pain perception. We utilized chronic calcium imaging of spinal dorsal horn neurons to determine how ... ...

    Abstract Pain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain and alters pain perception. We utilized chronic calcium imaging of spinal dorsal horn neurons to determine how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy conditions, we identify stable, narrowly tuned outputs selective for cooling or warming, and a neuronal ensemble activated by intense/noxious thermal and mechanical stimuli. Induction of an acute peripheral sensitization with capsaicin selectively and transiently retunes nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury-induced neuropathic pain results in a persistent suppression of innocuous spinal outputs coupled with activation of a normally silent population of high-threshold neurons. These results demonstrate the differential modulation of specific spinal outputs to the brain during nociceptive and neuropathic pain states.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.08.588581
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  2. Article ; Online: DeepEthogram, a machine learning pipeline for supervised behavior classification from raw pixels.

    Bohnslav, James P / Wimalasena, Nivanthika K / Clausing, Kelsey J / Dai, Yu Y / Yarmolinsky, David A / Cruz, Tomás / Kashlan, Adam D / Chiappe, M Eugenia / Orefice, Lauren L / Woolf, Clifford J / Harvey, Christopher D

    eLife

    2021  Volume 10

    Abstract: Videos of animal behavior are used to quantify researcher-defined behaviors of interest to study neural function, gene mutations, and pharmacological therapies. Behaviors of interest are often scored manually, which is time-consuming, limited to few ... ...

    Abstract Videos of animal behavior are used to quantify researcher-defined behaviors of interest to study neural function, gene mutations, and pharmacological therapies. Behaviors of interest are often scored manually, which is time-consuming, limited to few behaviors, and variable across researchers. We created DeepEthogram: software that uses supervised machine learning to convert raw video pixels into an ethogram, the behaviors of interest present in each video frame. DeepEthogram is designed to be general-purpose and applicable across species, behaviors, and video-recording hardware. It uses convolutional neural networks to compute motion, extract features from motion and images, and classify features into behaviors. Behaviors are classified with above 90% accuracy on single frames in videos of mice and flies, matching expert-level human performance. DeepEthogram accurately predicts rare behaviors, requires little training data, and generalizes across subjects. A graphical interface allows beginning-to-end analysis without end-user programming. DeepEthogram's rapid, automatic, and reproducible labeling of researcher-defined behaviors of interest may accelerate and enhance supervised behavior analysis. Code is available at: https://github.com/jbohnslav/deepethogram.
    MeSH term(s) Animals ; Drosophila melanogaster ; Female ; Grooming ; Humans ; Image Processing, Computer-Assisted ; Kinetics ; Male ; Mice, Inbred C57BL ; Motor Activity ; Neural Networks, Computer ; Pattern Recognition, Automated ; Reproducibility of Results ; Social Behavior ; Supervised Machine Learning ; Video Recording ; Walking ; Mice
    Language English
    Publishing date 2021-09-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.63377
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  3. Article ; Online: Coding and Plasticity in the Mammalian Thermosensory System.

    Yarmolinsky, David A / Peng, Yueqing / Pogorzala, Leah A / Rutlin, Michael / Hoon, Mark A / Zuker, Charles S

    Neuron

    2016  Volume 92, Issue 5, Page(s) 1079–1092

    Abstract: Perception of the thermal environment begins with the activation of peripheral thermosensory neurons innervating the body surface. To understand how temperature is represented in vivo, we used genetically encoded calcium indicators to measure temperature- ...

    Abstract Perception of the thermal environment begins with the activation of peripheral thermosensory neurons innervating the body surface. To understand how temperature is represented in vivo, we used genetically encoded calcium indicators to measure temperature-evoked responses in hundreds of neurons across the trigeminal ganglion. Our results show how warm, hot, and cold stimuli are represented by distinct population responses, uncover unique functional classes of thermosensory neurons mediating heat and cold sensing, and reveal the molecular logic for peripheral warmth sensing. Next, we examined how the peripheral somatosensory system is functionally reorganized to produce altered perception of the thermal environment after injury. We identify fundamental transformations in sensory coding, including the silencing and recruitment of large ensembles of neurons, providing a cellular basis for perceptual changes in temperature sensing, including heat hypersensitivity, persistence of heat perception, cold hyperalgesia, and cold analgesia.
    MeSH term(s) Animals ; Burns/metabolism ; Burns/physiopathology ; Cold Temperature ; Hot Temperature ; Hyperalgesia/metabolism ; Hyperalgesia/physiopathology ; Hyperesthesia/metabolism ; Hyperesthesia/physiopathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neuronal Plasticity ; Neurons/metabolism ; Neurons/physiology ; TRPA1 Cation Channel ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; Thermosensing/physiology ; Transient Receptor Potential Channels/genetics ; Transient Receptor Potential Channels/metabolism ; Trigeminal Ganglion/cytology ; Trigeminal Ganglion/metabolism ; Trigeminal Ganglion/physiology
    Chemical Substances TRPA1 Cation Channel ; TRPM Cation Channels ; TRPM8 protein, mouse ; TRPV Cation Channels ; TRPV1 protein, mouse ; Transient Receptor Potential Channels ; Trpa1 protein, mouse
    Language English
    Publishing date 2016-11-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2016.10.021
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2496: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  4. Article ; Online: Automated preclinical detection of mechanical pain hypersensitivity and analgesia.

    Zhang, Zihe / Roberson, David P / Kotoda, Masakazu / Boivin, Bruno / Bohnslav, James P / González-Cano, Rafael / Yarmolinsky, David A / Turnes, Bruna Lenfers / Wimalasena, Nivanthika K / Neufeld, Shay Q / Barrett, Lee B / Quintão, Nara L M / Fattori, Victor / Taub, Daniel G / Wiltschko, Alexander B / Andrews, Nick A / Harvey, Christopher D / Datta, Sandeep Robert / Woolf, Clifford J

    Pain

    2022  Volume 163, Issue 12, Page(s) 2326–2336

    Abstract: Abstract: The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here, we demonstrate a novel data acquisition and analysis ... ...

    Abstract Abstract: The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here, we demonstrate a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely behaving mice, in the dark, over extended periods for continuous acquisition of 2 parallel video data streams: (1) near-infrared frustrated total internal reflection for detecting the degree, force, and timing of surface contact and (2) simultaneous ongoing video graphing of whole-body pose. Using machine vision and machine learning, we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period and scalable for high-throughput preclinical analgesic efficacy assessment.
    MeSH term(s) Mice ; Animals ; Pain/diagnosis ; Pain/drug therapy ; Analgesia ; Pain Management ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Pain Measurement
    Chemical Substances Analgesics
    Language English
    Publishing date 2022-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002680
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    Zs.A 1158: Show issues Location:
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  5. Article ; Online: Common sense about taste: from mammals to insects.

    Yarmolinsky, David A / Zuker, Charles S / Ryba, Nicholas J P

    Cell

    2009  Volume 139, Issue 2, Page(s) 234–244

    Abstract: The sense of taste is a specialized chemosensory system dedicated to the evaluation of food and drink. Despite the fact that vertebrates and insects have independently evolved distinct anatomic and molecular pathways for taste sensation, there are clear ... ...

    Abstract The sense of taste is a specialized chemosensory system dedicated to the evaluation of food and drink. Despite the fact that vertebrates and insects have independently evolved distinct anatomic and molecular pathways for taste sensation, there are clear parallels in the organization and coding logic between the two systems. There is now persuasive evidence that tastant quality is mediated by labeled lines, whereby distinct and strictly segregated populations of taste receptor cells encode each of the taste qualities.
    MeSH term(s) Animals ; Chemoreceptor Cells/physiology ; Insecta/physiology ; Mammals/physiology ; Taste ; Taste Buds/physiology ; Tongue/cytology ; Tongue/physiology
    Language English
    Publishing date 2009-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2009.10.001
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    Zs.A 1167: Show issues Location:
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    Zs.MG 58: Show issues

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  6. Article ; Online: The neural representation of taste quality at the periphery.

    Barretto, Robert P J / Gillis-Smith, Sarah / Chandrashekar, Jayaram / Yarmolinsky, David A / Schnitzer, Mark J / Ryba, Nicholas J P / Zuker, Charles S

    Nature

    2014  Volume 517, Issue 7534, Page(s) 373–376

    Abstract: The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and ... ...

    Abstract The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.
    MeSH term(s) Animals ; Calcium/metabolism ; Geniculate Ganglion/cytology ; Mice ; Mice, Transgenic ; Neurons/physiology ; Taste/physiology ; Taste Buds/cytology ; Taste Buds/physiology ; Taste Perception/physiology ; Tongue/cytology ; Tongue/innervation ; Tongue/physiology
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2014-11-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature13873
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    Zs.MO 244: Show issues

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  7. Article ; Online: The cells and peripheral representation of sodium taste in mice.

    Chandrashekar, Jayaram / Kuhn, Christina / Oka, Yuki / Yarmolinsky, David A / Hummler, Edith / Ryba, Nicholas J P / Zuker, Charles S

    Nature

    2010  Volume 464, Issue 7286, Page(s) 297–301

    Abstract: Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion. Notably, ...

    Abstract Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts. Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system. Previously, we showed that four of the five basic taste qualities-sweet, sour, bitter and umami-are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCalpha in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.
    MeSH term(s) Animals ; Behavior/physiology ; Epithelial Sodium Channels/genetics ; Epithelial Sodium Channels/metabolism ; Mice ; Mice, Transgenic ; Sodium/physiology ; Taste/genetics ; Taste Buds/cytology ; Taste Buds/metabolism ; Taste Buds/physiology
    Chemical Substances Epithelial Sodium Channels ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2010-01-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature08783
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
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