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  1. Article: Neural substrates of cold nociception in

    Patel, Atit A / Cardona, Albert / Cox, Daniel N

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate ... ...

    Abstract Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.31.551339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Modality specific roles for metabotropic GABAergic signaling and calcium induced calcium release mechanisms in regulating cold nociception.

    Patel, Atit A / Sakurai, Akira / Himmel, Nathaniel J / Cox, Daniel N

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 942548

    Abstract: ... Calcium ( ... ...

    Abstract Calcium (Ca
    Language English
    Publishing date 2022-09-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.942548
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  3. Article: Behavioral and Functional Assays for Investigating Mechanisms of Noxious Cold Detection and Multimodal Sensory Processing in

    Patel, Atit A / Cox, Daniel N

    Bio-protocol

    2017  Volume 7, Issue 13

    Abstract: To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural ... ...

    Abstract To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling
    Language English
    Publishing date 2017-08-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.2388
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  4. Article: PP2A phosphatase regulates cell-type specific cytoskeletal organization to drive dendrite diversity.

    Bhattacharjee, Shatabdi / Lottes, Erin N / Nanda, Sumit / Golshir, Andre / Patel, Atit A / Ascoli, Giorgio A / Cox, Daniel N

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 926567

    Abstract: Uncovering molecular mechanisms regulating dendritic diversification is essential to understanding the formation and modulation of functional neural circuitry. Transcription factors play critical roles in promoting dendritic diversity and here, we ... ...

    Abstract Uncovering molecular mechanisms regulating dendritic diversification is essential to understanding the formation and modulation of functional neural circuitry. Transcription factors play critical roles in promoting dendritic diversity and here, we identify PP2A phosphatase function as a downstream effector of Cut-mediated transcriptional regulation of dendrite development. Mutant analyses of the PP2A catalytic subunit (
    Language English
    Publishing date 2022-11-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.926567
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  5. Article ; Online: Chloride-dependent mechanisms of multimodal sensory discrimination and nociceptive sensitization in

    Himmel, Nathaniel J / Sakurai, Akira / Patel, Atit A / Bhattacharjee, Shatabdi / Letcher, Jamin M / Benson, Maggie N / Gray, Thomas R / Cymbalyuk, Gennady S / Cox, Daniel N

    eLife

    2023  Volume 12

    Abstract: Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for ... ...

    Abstract Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for organismal survival. Moreover, disruptions in the capacity to differentiate between noxious and innocuous stimuli can result in neuropathic pain.
    MeSH term(s) Animals ; Drosophila/physiology ; Chlorides ; Drosophila Proteins/metabolism ; Nociception/physiology ; Nociceptors/physiology ; Sensory Receptor Cells/physiology ; Neuralgia ; Anoctamins
    Chemical Substances Chlorides ; Drosophila Proteins ; Anoctamins
    Language English
    Publishing date 2023-01-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.76863
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  6. Article: CCT and Cullin1 regulate the TORC1 pathway to promote dendritic arborization in health and disease.

    Lottes, Erin N / Ciger, Feyza H / Bhattacharjee, Shatabdi / Timmins-Wilde, Emily A / Tete, Benoit / Tran, Tommy / Matta, Jais / Patel, Atit A / Cox, Daniel N

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the regulatory relationship between the cytosolic chaperonin CCT, key insulin pathway genes, ... ...

    Abstract The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the regulatory relationship between the cytosolic chaperonin CCT, key insulin pathway genes, and an E3 ubiquitin ligase (Cullin1) in homeostatic dendritic development. CCT loss of function (LOF) results in dendritic hypotrophy in
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.31.551324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Injury-induced cold sensitization in Drosophila larvae involves behavioral shifts that require the TRP channel Brv1.

    Turner, Heather N / Patel, Atit A / Cox, Daniel N / Galko, Michael J

    PloS one

    2018  Volume 13, Issue 12, Page(s) e0209577

    Abstract: Nociceptive sensitization involves an increase in responsiveness of pain sensing neurons to sensory stimuli, typically through the lowering of their nociceptive threshold. Nociceptive sensitization is common following tissue damage, inflammation, and ... ...

    Abstract Nociceptive sensitization involves an increase in responsiveness of pain sensing neurons to sensory stimuli, typically through the lowering of their nociceptive threshold. Nociceptive sensitization is common following tissue damage, inflammation, and disease and serves to protect the affected area while it heals. Organisms can become sensitized to a range of noxious and innocuous stimuli, including thermal stimuli. The basic mechanisms underlying sensitization to warm or painfully hot stimuli have begun to be elucidated, however, sensitization to cold is not well understood. Here, we develop a Drosophila assay to study cold sensitization after UV-induced epidermal damage in larvae. Larvae respond to acute cold stimuli with a set of unique behaviors that include a contraction of the head and tail (CT) or a raising of the head and tail into a U-Shape (US). Under baseline, non-injured conditions larvae primarily produce a CT response to an acute cold (10°C) stimulus, however, we show that cold-evoked responses shift following tissue damage: CT responses decrease, US responses increase and some larvae exhibit a lateral body roll (BR) that is typically only observed in response to high temperature and noxious mechanical stimuli. At the cellular level, class III neurons are required for the decrease in CT, chordotonal neurons are required for the increase in US, and chordotonal and class IV neurons are required for the appearance of BR responses after UV. At the molecular level, we found that the transient receptor potential (TRP) channel brivido-1 (brv1) is required for these behavioral shifts. Our Drosophila model will allow us to precisely identify the genes and circuits involved in cold nociceptive sensitization.
    MeSH term(s) Animals ; Behavior, Animal ; Calcium-Binding Proteins/physiology ; Cold Injury/genetics ; Cold Injury/physiopathology ; Cold Temperature/adverse effects ; Dendrites/genetics ; Dendrites/metabolism ; Disease Models, Animal ; Drosophila Proteins/physiology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/physiology ; Humans ; Hyperalgesia/genetics ; Hyperalgesia/physiopathology ; Larva/genetics ; Larva/physiology ; Sensory Receptor Cells/metabolism ; Sensory Receptor Cells/physiology ; Transient Receptor Potential Channels/genetics
    Chemical Substances Calcium-Binding Proteins ; Drosophila Proteins ; Transient Receptor Potential Channels ; brv1 protein, Drosophila
    Language English
    Publishing date 2018-12-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0209577
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  8. Article ; Online: Drosophila

    Im, Seol Hee / Patel, Atit A / Cox, Daniel N / Galko, Michael J

    Disease models & mechanisms

    2018  Volume 11, Issue 5

    Abstract: Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes- ... ...

    Abstract Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used
    MeSH term(s) Animals ; Calcium/metabolism ; Dendrites/metabolism ; Dendrites/radiation effects ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/pathology ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/radiation effects ; Hyperalgesia/metabolism ; Hyperalgesia/pathology ; Insulin/metabolism ; Larva/metabolism ; Larva/radiation effects ; Models, Biological ; Mutation/genetics ; Nociception/radiation effects ; Nociceptors/metabolism ; Nociceptors/radiation effects ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Sensory Receptor Cells/metabolism ; Sensory Receptor Cells/radiation effects ; Signal Transduction ; Ultraviolet Rays
    Chemical Substances Drosophila Proteins ; Insulin ; InR protein, Drosophila (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-05-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2451104-3
    ISSN 1754-8411 ; 1754-8403
    ISSN (online) 1754-8411
    ISSN 1754-8403
    DOI 10.1242/dmm.034231
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  9. Article ; Online: Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats.

    Althammer, Ferdinand / Ferreira-Neto, Hildebrando Candido / Rubaharan, Myurajan / Roy, Ranjan K / Patel, Atit A / Murphy, Anne / Cox, Daniel N / Stern, Javier E

    Journal of neuroinflammation

    2020  Volume 17, Issue 1, Page(s) 221

    Abstract: Background: Cardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, ... ...

    Abstract Background: Cardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, and anxiety. While neuroinflammation in the hypothalamic paraventricular nucleus contributes to autonomic and cardiovascular dysregulation in heart failure, mechanisms underlying cognitive and mood disorders in this disease remain elusive. The goal of this study was to quantitatively assess markers of neuroinflammation (glial morphology, cytokines, and A1 astrocyte markers) in the central amygdala, a critical forebrain region involved in emotion and cognition, and to determine its time course and correlation to disease severity during the progression of heart failure.
    Methods: We developed and implemented a comprehensive microglial/astrocyte profiler for precise three-dimensional morphometric analysis of individual microglia and astrocytes in specific brain nuclei at different time points during the progression of heart failure. To this end, we used a well-established ischemic heart failure rat model. Morphometric studies were complemented with quantification of various pro-inflammatory cytokines and A1/A2 astrocyte markers via qPCR.
    Results: We report structural remodeling of central amygdala microglia and astrocytes during heart failure that affected cell volume, surface area, filament length, and glial branches, resulting overall in somatic swelling and deramification, indicative of a change in glial state. These changes occurred in a time-dependent manner, correlated with the severity of heart failure, and were delayed compared to changes in the hypothalamic paraventricular nucleus. Morphometric changes correlated with elevated mRNA levels of pro-inflammatory cytokines and markers of reactive A1-type astrocytes in the paraventricular nucleus and central amygdala during heart failure.
    Conclusion: We provide evidence that in addition to the previously described hypothalamic neuroinflammation implicated in sympathohumoral activation during heart failure, microglia, and astrocytes within the central amygdala also undergo structural remodeling indicative of glial shifts towards pro-inflammatory phenotypes. Thus, our studies suggest that neuroinflammation in the amygdala stands as a novel pathophysiological mechanism and potential therapeutic target that could be associated with emotional and cognitive deficits commonly observed at later stages during the course of heart failure.
    MeSH term(s) Animals ; Astrocytes/pathology ; Central Amygdaloid Nucleus/pathology ; Heart Failure/complications ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Male ; Microglia/pathology ; Microscopy, Confocal/methods ; Paraventricular Hypothalamic Nucleus/pathology ; Rats ; Rats, Wistar
    Language English
    Publishing date 2020-07-23
    Publishing country England
    Document type Journal Article
    ISSN 1742-2094
    ISSN (online) 1742-2094
    DOI 10.1186/s12974-020-01892-4
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  10. Article ; Online: Correction to: Three-dimensional morphometric analysisreveals time-dependent structural changesin microglia and astrocytes in the centralamygdala and hypothalamicparaventricular nucleus of heart failure rats.

    Althammer, Ferdinand / Ferreira-Neto, Hildebrando Candido / Rubaharan, Myurajan / Roy, Ranjan K / Patel, Atit A / Murphy, Anne / Cox, Daniel N / Stern, Javier E

    Journal of neuroinflammation

    2020  Volume 17, Issue 1, Page(s) 348

    Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

    Abstract An amendment to this paper has been published and can be accessed via the original article.
    Language English
    Publishing date 2020-11-22
    Publishing country England
    Document type Published Erratum
    ISSN 1742-2094
    ISSN (online) 1742-2094
    DOI 10.1186/s12974-020-02035-5
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