44 results on '"Quirk G"'
Search Results
2. FACILITATING (AND INDUCING) MEMORY FOR FEAR EXTINCTION: S22-02
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Quirk, G. J., Peters, J. L., Rosas-Vidal, L. E., Rodriguez-Romaguera, J., and Do Monte, F. H.
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- 2011
3. Firing relations of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats
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Stewart, M., Quirk, G. J., Barry, M., and Fox, S. E.
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- 1992
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4. Electrical Stimulation of Medial Prefrontal Cortex Reduces Conditioned Fear in a Temporally Specific Manner
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Milad, M R., Vidal-Gonzalez, I, and Quirk, G J.
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- 2004
5. Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (II). Effects on the adrenergic nervous system.
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Chan, Peter S., Cervoni, Peter, Accomando, Richard C., Quirk, Gerald J., Ronsberg, Margaret A., Chan, P S, Cervoni, P, Accomando, R C, Quirk, G J, and Ronsberg, M A
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- 1986
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6. Studies of the antihypertensive effects of CL 242,817, a new angiotensin-I converting enzyme inhibitor [S−(R*, s*)]-1-[(3-acetylthio)-3-benzoyl-2-methyl propionyl-L-proline].
- Author
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Lai, F. M., Cervoni, P., Chan, P. S., Shepherd, C. A., Ronsberg, M. A., Quirk, G. J., Thibault, L., Scully, P., and Tanikella, T.
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- 1985
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7. Some in vitro and in vivo studies of a new angiotensin I-converting enzyme inhibitor [[S-(R*), S*]-1-[(3-acetylthio)-3-benzoyl-2-methylpropionyl]-L-proline] (CL 242,817) in comparison with captopril.
- Author
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Lai, F. M., Cervoni, P., Tanikella, T., Shepherd, C., Quirk, G., Herzlinger, H., and Stubbs, C. S.
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- 1983
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8. 189: Rapid closure of mid-gestational excisional wounds is associated with alterations in collagen types 1Α1 and 3 gene expression
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Goldberg, S.R., Quirk, G., Sykes, V., and Lanning, D.A.
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- 2007
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9. Anesthetic Management for Cesarean Section in a Patient with Charcot-Marie-Tooth Disease.
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Brown, J. E., Boyles, G. D., Quirk, G., and Clark, R. B.
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- 1987
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10. Sensitive SARS-CoV-2 salivary antibody assays for clinical saline gargle samples using smartphone-based competitive particle immunoassay platforms.
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Liang Y, Buchanan BC, Khanthaphixay B, Zhou A, Quirk G, Worobey M, and Yoon JY
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- Humans, SARS-CoV-2, Smartphone, Antibodies, Viral, Immunoglobulin G, Immunoassay, COVID-19 diagnosis, Biosensing Techniques
- Abstract
Antibody assay for SARS-CoV-2 has become increasingly important to track latent and asymptomatic infections, check the individual's immune status, and confirm vaccine efficacy and durability. However, current SARS-CoV-2 antibody assays require invasive blood collection, requiring a remote laboratory and a trained phlebotomist. Direct detection of SARS-CoV-2 antibodies from clinical saline gargle samples has been considered challenging due to the smaller number of antibodies in such specimens and the high limit of detection of currently available rapid tests. This work demonstrates simple and non-invasive methods for detecting SARS-CoV-2 salivary antibodies. Competitive particle immunoassays were developed on a paper microfluidic chip using the receptor-binding domain (RBD) antigens on spike proteins. Using a smartphone, they were monitored by counting the captured fluorescent particles or evaluating the capillary flow velocities. The limit of detection (LOD), cross-binding between alpha- and omicron-strains, and the effect of angiotensin-converting enzyme 2 (ACE2) presence were investigated. LODs were 1-5 ng/mL in both 10% and 1% saliva. Clinical saline gargle samples were assayed using both methods, showing a statistical difference between virus-negative and virus-positive samples, although the assays targeted antibodies. Only a small number of virus-positive samples were antibody-negative. The high assay sensitivity detected a small number of antibodies developed even during the early phase of infections. Overall, this work demonstrates the ability to detect SARS-CoV-2 salivary IgG antibodies on simple, cost-effective, portable platforms towards mitigating SARS-CoV-2 and potentially other respiratory viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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11. Smartphone-based sensitive detection of SARS-CoV-2 from saline gargle samples via flow profile analysis on a paper microfluidic chip.
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Akarapipad P, Kaarj K, Breshears LE, Sosnowski K, Baker J, Nguyen BT, Eades C, Uhrlaub JL, Quirk G, Nikolich-Žugich J, Worobey M, and Yoon JY
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- Humans, Microfluidics, SARS-CoV-2, Smartphone, Biosensing Techniques, COVID-19 diagnosis, Influenza A Virus, H1N1 Subtype
- Abstract
Respiratory viruses, especially coronaviruses, have resulted in worldwide pandemics in the past couple of decades. Saliva-based paper microfluidic assays represent an opportunity for noninvasive and rapid screening, yet both the sample matrix and test method come with unique challenges. In this work, we demonstrated the rapid and sensitive detection of SARS-CoV-2 from saliva samples, which could be simpler and more comfortable for patients than existing methods. Furthermore, we systematically investigated the components of saliva samples that affected assay performance. Using only a smartphone, an antibody-conjugated particle suspension, and a paper microfluidic chip, we made the assay user-friendly with minimal processing. Unlike the previously established flow rate assays that depended solely on the flow rate or distance, this unique assay analyzes the flow profile to determine infection status. Particle-target immunoagglutination changed the surface tension and subsequently the capillary flow velocity profile. A smartphone camera automatically measured the flow profile using a Python script, which was not affected by ambient light variations. The limit of detection (LOD) was 1 fg/μL SARS-CoV-2 from 1% saliva samples and 10 fg/μL from simulated saline gargle samples (15% saliva and 0.9% saline). This method was highly specific as demonstrated using influenza A/H1N1. The sample-to-answer assay time was <15 min, including <1-min capillary flow time. The overall accuracy was 89% with relatively clean clinical saline gargle samples. Despite some limitations with turbid clinical samples, this method presents a potential solution for rapid mass testing techniques during any infectious disease outbreak as soon as the antibodies become available., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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12. Sensitive, smartphone-based SARS-CoV-2 detection from clinical saline gargle samples.
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Breshears LE, Nguyen BT, Akarapipad P, Sosnowski K, Kaarj K, Quirk G, Uhrlaub JL, Nikolich-Žugich J, Worobey M, and Yoon JY
- Abstract
Saliva specimens have drawn interest for diagnosing respiratory viral infections due to their ease of collection and decreased risk to healthcare providers. However, rapid and sensitive immunoassays have not yet been satisfactorily demonstrated for such specimens due to their viscosity and low viral loads. Using paper microfluidic chips and a smartphone-based fluorescence microscope, we developed a highly sensitive, low-cost immunofluorescence particulometric SARS-CoV-2 assay from clinical saline gargle samples. We demonstrated the limit of detection of 10 ag/μL. With easy-to-collect saline gargle samples, our clinical sensitivity, specificity, and accuracy were 100%, 86%, and 93%, respectively, for n = 27 human subjects with n = 13 RT-qPCR positives., (© The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences.)
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- 2022
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13. Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors.
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Shroff RT, Chalasani P, Wei R, Pennington D, Quirk G, Schoenle MV, Peyton KL, Uhrlaub JL, Ripperger TJ, Jergović M, Dalgai S, Wolf A, Whitmer R, Hammad H, Carrier A, Scott AJ, Nikolich-Žugich J, Worobey M, Sprissler R, Dake M, LaFleur BJ, and Bhattacharya D
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- Adult, Aged, Antibodies, Viral blood, Antibodies, Viral metabolism, Arizona, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines immunology, Cohort Studies, Dose-Response Relationship, Drug, Female, Humans, Immunity, Humoral drug effects, Immunity, Humoral physiology, Male, Middle Aged, Neoplasms immunology, Neoplasms pathology, RNA, Messenger immunology, RNA, Viral immunology, SARS-CoV-2 genetics, SARS-CoV-2 immunology, Young Adult, BNT162 Vaccine administration & dosage, BNT162 Vaccine immunology, COVID-19 prevention & control, Neoplasms therapy
- Abstract
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2021
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14. Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy.
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Shroff RT, Chalasani P, Wei R, Pennington D, Quirk G, Schoenle MV, Peyton KL, Uhrlaub JL, Ripperger TJ, Jergović M, Dalgai S, Wolf A, Whitmer R, Hammad H, Carrier A, Scott AJ, Nikolich-Žugich J, Worobey M, Sprissler R, Dake M, LaFleur BJ, and Bhattacharya D
- Abstract
Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN γ + Spike-specific T cells. Yet the magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. We initiated an interventional phase 1 trial of a third booster shot (NCT04936997); primary outcomes were immune responses with a secondary outcome of safety. After a third immunization, the 20 participants demonstrated an increase in antibody responses, with a median 3-fold increase in virus-neutralizing titers. Yet no improvement was observed in T cell responses at 1 week after the booster immunization. There were mild adverse events, primarily injection site myalgia, with no serious adverse events after a month of follow-up. These results suggest that a third vaccination improves humoral immunity against COVID-19 in cancer patients on active chemotherapy with no severe adverse events., Competing Interests: Competing interests: Sana Biotechnology has licensed intellectual property of D.B. and Washington University in St. Louis. D.B. is a co-founder of Clade Therapeutics. B.J.L. has a financial interest in Cofactor Genomics, Inc. and Iron Horse Dx. P.C. receives research funding from Pfizer, BioAtla, Zentalis, Genentech, Eli-Lilly, Phoenix Molecular Designs, Amgen, Radius Pharmaceuticals, Carrick Therapeutics, and Angiochem and served on advisory boards for Novartis, Eli Lilly, Zentalis, Astra-Zeneca, Amgen, Bayer, Asthenex, Prosigna, Heron, Puma Biotechnology and Oncosec. R.T.S. receives research funding from Merck, Rafael Pharmaceuticals, ImmunoVaccine, Bayer, SeaGen, Exelixis, Pieris, LOXO Oncology, Novocure, NuCana, QED and has served as a consultant/advisor to Merck, Servier, Astra-Zeneca, EMD Serono, Taiho, QED, Incyte, Genentech, Basilea.
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- 2021
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15. An Early Pandemic Analysis of SARS-CoV-2 Population Structure and Dynamics in Arizona.
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Ladner JT, Larsen BB, Bowers JR, Hepp CM, Bolyen E, Folkerts M, Sheridan K, Pfeiffer A, Yaglom H, Lemmer D, Sahl JW, Kaelin EA, Maqsood R, Bokulich NA, Quirk G, Watts TD, Komatsu KK, Waddell V, Lim ES, Caporaso JG, Engelthaler DM, Worobey M, and Keim P
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- Arizona epidemiology, Betacoronavirus classification, Betacoronavirus isolation & purification, COVID-19, Coronavirus Infections virology, Evolution, Molecular, Genome, Viral genetics, Humans, Incidence, Mutation, Pandemics, Phylogeny, Pneumonia, Viral virology, SARS-CoV-2, Viral Proteins genetics, Betacoronavirus genetics, Coronavirus Infections epidemiology, Coronavirus Infections transmission, Pneumonia, Viral epidemiology, Pneumonia, Viral transmission
- Abstract
In December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan, China, causing severe morbidity and mortality. Since then, the virus has swept across the globe, causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus in Arizona, we sequenced viral genomes from clinical samples tested at the TGen North Clinical Laboratory, the Arizona Department of Health Services, and those collected as part of community surveillance projects at Arizona State University and the University of Arizona. Phylogenetic analysis of 84 genomes from across Arizona revealed a minimum of 11 distinct introductions inferred to have occurred during February and March. We show that >80% of our sequences descend from strains that were initially circulating widely in Europe but have since dominated the outbreak in the United States. In addition, we show that the first reported case of community transmission in Arizona descended from the Washington state outbreak that was discovered in late February. Notably, none of the observed transmission clusters are epidemiologically linked to the original travel-related case in the state, suggesting successful early isolation and quarantine. Finally, we use molecular clock analyses to demonstrate a lack of identifiable, widespread cryptic transmission in Arizona prior to the middle of February 2020. IMPORTANCE As the COVID-19 pandemic swept across the United States, there was great differential impact on local and regional communities. One of the earliest and hardest hit regions was in New York, while at the same time Arizona (for example) had low incidence. That situation has changed dramatically, with Arizona now having the highest rate of disease increase in the country. Understanding the roots of the pandemic during the initial months is essential as the pandemic continues and reaches new heights. Genomic analysis and phylogenetic modeling of SARS-COV-2 in Arizona can help to reconstruct population composition and predict the earliest undetected introductions. This foundational work represents the basis for future analysis and understanding as the pandemic continues., (Copyright © 2020 Ladner et al.)
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- 2020
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16. Functional disruption in prefrontal-striatal network in obsessive-compulsive disorder.
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Sha Z, Versace A, Edmiston EK, Fournier J, Graur S, Greenberg T, Santos JPL, Chase HW, Stiffler RS, Bonar L, Hudak R, Yendiki A, Greenberg BD, Rasmussen S, Liu H, Quirk G, Haber S, and Phillips ML
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- Adult, Amygdala physiopathology, Case-Control Studies, Cerebral Cortex physiopathology, Corpus Striatum diagnostic imaging, Corpus Striatum physiopathology, Female, Gyrus Cinguli physiopathology, Humans, Male, Nerve Net diagnostic imaging, Obsessive-Compulsive Disorder diagnostic imaging, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex physiopathology, Thalamus physiopathology, Young Adult, Magnetic Resonance Imaging, Nerve Net physiopathology, Obsessive-Compulsive Disorder physiopathology, Severity of Illness Index
- Abstract
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants. We then examined relationships between OCD neural network connectivity and OCD symptom severity in OCD participants. OCD relative to healthy participants showed significantly greater connectivity between the left caudate and bilateral dorsolateral prefrontal cortex. We also found a positive correlation between left caudate-bilateral dorsolateral prefrontal cortex connectivity and depression scores in OCD participants, such that greater positive connectivity was associated with more severe symptoms. This study makes a significant contribution to our understanding of functional networks and their relationship with depression in OCD., Competing Interests: Declaration of Competing Interest The authors report no biomedical financial interests or potential conflicts of interest., (Published by Elsevier B.V.)
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- 2020
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17. Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder.
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Sha Z, Edmiston EK, Versace A, Fournier JC, Graur S, Greenberg T, Lima Santos JP, Chase HW, Stiffler RS, Bonar L, Hudak R, Yendiki A, Greenberg BD, Rasmussen S, Liu H, Quirk G, Haber S, and Phillips ML
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- Adult, Brain, Cerebellum, Humans, Magnetic Resonance Imaging, Cerebral Cortex diagnostic imaging, Obsessive-Compulsive Disorder
- Abstract
Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. Neuroimaging studies have implicated altered connectivity among the functional networks of the cerebral cortex in the pathophysiology of OCD. However, there has been no comprehensive investigation of the cross-talk between the cerebellum and functional networks in the cerebral cortex., Methods: This functional neuroimaging study was completed by 44 adult participants with OCD and 43 healthy control participants. We performed large-scale data-driven brain network analysis to identify functional connectivity patterns using resting-state functional magnetic resonance imaging data., Results: Participants with OCD showed lower functional connectivity within the somatomotor network and greater functional connectivity among the somatomotor network, cerebellum, and subcortical network (e.g., thalamus and pallidum; all p < .005). Network-based statistics analyses demonstrated one component comprising connectivity within the somatomotor network that showed lower connectivity and a second component comprising connectivity among the somatomotor network, and motor regions in particular, and the cerebellum that showed greater connectivity in participants with OCD relative to healthy control participants. In participants with OCD, abnormal connectivity across both network-based statistics-derived components positively correlated with OCD symptom severity (p = .006)., Conclusions: To our knowledge, this study is the first comprehensive investigation of large-scale network alteration across the cerebral cortex, subcortical regions, and cerebellum in OCD. Our findings highlight a critical role of the cerebellum in the pathophysiology of OCD., (Published by Elsevier Inc.)
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- 2020
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18. Integrating neuroscience and learning: now's the time...
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Sah P, Fanselow M, Hattie J, Magsamen S, Mattingley J, Quirk G, and Williams S
- Abstract
Competing Interests: The authors declare no conflict of interest.
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- 2016
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19. Amphetamine sensitization is accompanied by an increase in prelimbic cortex activity.
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Aguilar-Rivera MI, Casanova JP, Gatica RI, Quirk GJ, and Fuentealba JA
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- Action Potentials drug effects, Animals, Cerebral Cortex physiology, Cerebral Cortex physiopathology, Male, Motor Activity drug effects, Neurons physiology, Rats, Sprague-Dawley, Amphetamine pharmacology, Central Nervous System Stimulants pharmacology, Cerebral Cortex drug effects, Neurons drug effects
- Abstract
Drug addiction is associated with dysfunction in the medial prefrontal cortex (mPFC). However, the modifications of neuronal activity in mPFC underlying the reinforcing properties of addictive drugs are still unclear. Here we carried out single-unit recording experiments to study the neuronal activity in the prelimbic (PL) cortex of anesthetized rats, after expression of locomotor sensitization to amphetamine. In control rats, an acute injection of amphetamine induced mainly an inhibitory effect on firing rate (FR) and this response was negatively correlated with the basal FR. Sensitized rats showed a higher proportion of excited neurons and the response to amphetamine was independent of basal FR. Moreover, in control rats, acute amphetamine decreased burst rate, whereas in sensitized rats acute amphetamine increased burst rate. These findings indicate that amphetamine sensitization renders mPFC neurons hyperexcitable. Taken together, these data support the hypothesis that early withdrawal is associated with an increase in the activity of the mPFC, which could strengthen the PL-Nucleus Accumbens connection, thus facilitating amphetamine-induced locomotor sensitization., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)
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- 2015
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20. Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory.
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Santini E, Muller RU, and Quirk GJ
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- Amygdala drug effects, Amygdala physiology, Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Conditioning, Classical drug effects, Conditioning, Classical physiology, Conditioning, Operant drug effects, Conditioning, Operant physiology, Excitatory Amino Acid Antagonists pharmacology, Extinction, Psychological drug effects, Fear physiology, Hippocampus drug effects, Hippocampus physiology, Learning drug effects, Long-Term Potentiation drug effects, Male, Memory drug effects, Mental Recall drug effects, N-Methylaspartate antagonists & inhibitors, Neuronal Plasticity drug effects, Neuronal Plasticity physiology, Piperazines pharmacology, Rats, Rats, Sprague-Dawley, Extinction, Psychological physiology, Learning physiology, Memory physiology, N-Methylaspartate metabolism
- Abstract
Extinction of conditioned fear to a tone paired with foot shock is thought to involve the formation of new memory. In support of this, previous studies have shown that extinction of conditioned fear depends on NMDA receptor-mediated plasticity. To further investigate the role of NMDA receptors in extinction, we examined the effects of the NMDA antagonist d(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) on the extinction of conditioned freezing and suppression of bar pressing (conditioned emotional response). Rats extinguished normally during a 90 min session in the presence of systemic CPP (10 mg/kg), but were unable to recall extinction learning 24 hr later. This suggests that an NMDA-independent form of plasticity supports short-term extinction memory, but NMDA receptors are required for consolidation processes leading to long-term extinction memory. Surprisingly, extinction learned in the presence of CPP was recalled normally when tested 48 hr after training, suggesting a delayed consolidation process that was able to improve memory in the absence of further training. Delayed consolidation involves NMDA receptors because CPP injected on the rest day between training and test prevented 48 hr recall of extinction learned under CPP. Control experiments showed that the effect of CPP on memory consolidation was not caused by state-dependent learning or reduced expression of freezing under CPP. These findings demonstrate that NMDA receptor activation is critical for consolidation of extinction learning and that this process can be initiated after training has taken place. We suggest that consolidation of extinction involves off-line relearning that reinforces extinction memory through NMDA-mediated plasticity, perhaps in prefrontal-amygdala circuits.
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- 2001
21. The role of ventromedial prefrontal cortex in the recovery of extinguished fear.
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Quirk GJ, Russo GK, Barron JL, and Lebron K
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- Animals, Avoidance Learning physiology, Conditioning, Psychological physiology, Denervation, Male, Neuropsychological Tests, Psychomotor Performance physiology, Rats, Rats, Sprague-Dawley, Time Factors, Extinction, Psychological physiology, Fear physiology, Prefrontal Cortex physiology
- Abstract
Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86%, which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.
- Published
- 2000
22. Neuroscience in developing countries: getting around the problems.
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Quirk GJ
- Subjects
- Humans, Public Opinion, Developing Countries, Neurosciences trends
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- 1999
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23. Differential effects of amygdala lesions on early and late plastic components of auditory cortex spike trains during fear conditioning.
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Armony JL, Quirk GJ, and LeDoux JE
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- Acoustic Stimulation, Action Potentials physiology, Amygdala surgery, Animals, Behavior, Animal physiology, Cognition physiology, Conditioning, Psychological physiology, Electrophysiology, Extinction, Psychological physiology, Male, Memory physiology, Rats, Rats, Sprague-Dawley, Reaction Time physiology, Amygdala physiopathology, Auditory Cortex physiology, Fear physiology, Neuronal Plasticity physiology
- Abstract
In auditory fear conditioning, pairing of a neutral acoustic conditioned stimulus (CS) with an aversive unconditioned stimulus (US) results in an enhancement of neural responses to the CS in the amygdala and auditory cortex. It is not clear, however, whether cortical plasticity governs neural changes in the amygdala or vice versa, or whether learning in these two structures is determined by independent processes. We examined this issue by recording single-cell activity in the auditory cortex (areas Te1, Te1v, and Te3) of freely behaving, amygdalectomized rats using a movable bundle of microwires. Amygdala damage did not affect short-latency (0-50 msec) tone responses, nor did it interfere with conditioning-induced increases of these onset responses. In contrast, lesions of the amygdala interfered with the development of late (500-1500 msec) conditioned tone responses that were not present before conditioning. Furthermore, whereas onset conditioned responses in the control group remained elevated after 30 extinction trials (presentation of CS alone), onset responses in lesioned animals returned to their preconditioning firing level after approximately 10 extinction trials. These results suggest that the amygdala enables the development of long-latency (US anticipatory) responses and prevents the extinction of short-latency onset responses to threatening stimuli. The findings further suggest that auditory cortex cells may participate differently in explicit and implicit memory networks.
- Published
- 1998
24. Fear research: implications for anxiety disorders.
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Quirk GJ
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- Amygdala physiology, Animals, Auditory Cortex physiology, Conditioning, Classical, Extinction, Psychological, Forecasting, Humans, Neurons physiology, Research, Anxiety Disorders psychology, Fear
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- 1998
25. Central somatosensory conduction time in severely growth-stunted children.
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Hesse H, Rivera MF, de Díaz I, and Quirk GJ
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- Child, Cohort Studies, Female, Humans, Male, Neural Conduction, Central Nervous System physiopathology, Evoked Potentials, Somatosensory physiology, Growth Disorders physiopathology, Nutrition Disorders physiopathology
- Abstract
To examine the effects of chronic malnutrition on central nervous system function, we used the somatosensory evoked potential to measure the central conduction time of 20 children aged 7-8 y with heights below the third percentile for their age and 20 control children in Honduras. The two groups differed significantly in socioeconomic status, achievement in Bender's neurointegrative test, and hematocrit, but not in birth weight. After median nerve stimulation, the mean central conduction time (interpeak latency between N13 and N20) for the growth-stunted group (6.19 +/- 0.52 ms) did not differ significantly from that of the control subjects (6.30 +/- 0.58 ms), suggesting appropriate myelination and fiber diameter. Somatosensory tracts may escape damage resulting from postnatal dietary deficiencies because myelination in these tracts is almost complete at birth.
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- 1998
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26. Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala.
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Quirk GJ, Armony JL, and LeDoux JE
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- Acoustic Stimulation, Action Potentials physiology, Amygdala physiology, Animals, Association Learning physiology, Auditory Cortex physiology, Extinction, Psychological physiology, Male, Memory physiology, Neural Pathways, Neurons physiology, Rats, Rats, Sprague-Dawley, Reaction Time physiology, Time Factors, Amygdala cytology, Auditory Cortex cytology, Conditioning, Classical physiology, Fear physiology
- Abstract
Single neurons were recorded in freely behaving rats during fear conditioning from areas of auditory cortex that project to the lateral nucleus of the amygdala (LA). The latency and rate of conditioning and extinction were analyzed, and the results were compared to previous recordings from LA itself. Auditory cortex neurons took more trials to learn, and they responded more slowly than LA neurons within trials. Short-latency plasticity in LA, therefore, reflects inputs from the auditory thalamus rather than the auditory cortex. Unlike LA cells, some auditory cortex cells showed late conditioned responses that seemed to anticipate the unconditioned stimulus, while others showed extinction-resistant memory storage. Thus, rapid conditioning of fear responses to potentially dangerous stimuli depends on plasticity in the amygdala, while cortical areas may be particularly involved in higher cognitive (mnemonic and attentional) processing of fear experiences.
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- 1997
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27. Science in developing countries: whose agenda?
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Quirk GJ and Weisskopf MG
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- Honduras, Humans, Research, Developing Countries, Neurophysiology
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- 1997
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28. Emotional memory: a search for sites of plasticity.
- Author
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Quirk GJ, Armony JL, Repa JC, Li XF, and LeDoux JE
- Subjects
- Animals, Brain physiology, Humans, Emotions physiology, Memory physiology, Neuronal Plasticity physiology
- Published
- 1996
29. Starting a neuroscience research laboratory in a developing country: a Fulbright experience in Honduras.
- Author
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Quirk GJ
- Subjects
- Budgets, Computers, Curriculum, Education, Medical, Graduate, Equipment and Supplies, Fellowships and Scholarships, Honduras, Humans, Neurophysiology education, Program Development, Schools, Medical, Social Problems, Students, Medical, Teaching, Developing Countries, Laboratories, Neurosciences education, Research
- Abstract
The first laboratory of neurophysiology was installed in the medical school of the University of Honduras during the 1992-1993 academic year. The goal of the project was to improve the teaching of physiology in the medical curriculum and to establish a neuroscience research laboratory able to address Honduran needs. In addition to a computer learning facility and wet labs in neurophysiology for medical students, an independent research program that focused on social problems in the country (for example, the effects of malnutrition on the developing central nervous system) was developed, paving the way for the first graduate program in physiology in Honduras. Funded by a Fulbright Lectureship Grant, the shoe-string budget was augmented by donations of equipment by colleagues. This first-hand account describes the planning and implementation of the project, covering both expected and unexpected problems and successes. An update on the progress of the lab after two years of independent operation is also described.
- Published
- 1995
- Full Text
- View/download PDF
30. Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat.
- Author
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Quirk GJ, Repa C, and LeDoux JE
- Subjects
- Acoustic Stimulation, Animals, Electrophysiology, Male, Neuronal Plasticity, Rats, Rats, Sprague-Dawley, Thalamus physiology, Amygdala physiology, Behavior, Animal physiology, Conditioning, Psychological, Fear, Neurons physiology
- Abstract
The lateral nucleus of the amygdala (LA) is the first site in the amygdala where the plasticity underlying fear conditioning could occur. We simultaneously recorded from multiple LA neurons in freely moving rats during fear conditioning trials in which tones were paired with foot shocks. Conditioning significantly increased the magnitude of tone-elicited responses (often within the first several trials), converted unresponsive cells into tone-responsive ones, and altered functional couplings between LA neurons. The effects of conditioning were greatest on the shortest latency (less than 15 ms) components of the tone-elicited responses, consistent with the hypothesis that direct projections from the auditory thalamus to LA are an important link in the circuitry through which rapid behavioral responses are controlled in the presence of conditioned fear stimuli.
- Published
- 1995
- Full Text
- View/download PDF
31. Early malnutrition followed by nutritional restoration lowers the conduction velocity and excitability of the corticospinal tract.
- Author
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Quirk GJ, Mejia WR, Hesse H, and Su H
- Subjects
- Analysis of Variance, Animals, Electric Conductivity, Electric Stimulation, Female, Male, Nutrition Disorders diet therapy, Rats, Rats, Wistar, Motor Cortex physiology, Nutrition Disorders physiopathology, Pyramidal Tracts physiopathology, Synaptic Transmission physiology
- Abstract
The physiological sequelae of undernutrition were investigated in rats that were undernourished from day 1-21 and subsequently free-fed to 75 days of age. Population responses were recorded in the corticospinal tract following surface stimulation of the motor cortex, which activates corticospinal cells directly, and also indirectly via cortical synapses. The conduction velocity of the fastest corticospinal fibers in 15 malnourished rats was 16.9 m/s, significantly slower (P < 0.001) than the 20.0 m/s observed in 26 controls. In addition, the excitability of corticospinal neurons to direct stimulation was reduced as much as 67% in malnourished rats, while no effect on synaptic activation was observed. Our findings suggest that early malnutrition reduces the number of large fibers in the adult corticospinal tract. These results are discussed with respect to known morphological and behavioral effects of malnutrition in rats and their relevance to humans.
- Published
- 1995
- Full Text
- View/download PDF
32. Stress disorders of families of the disappeared: a controlled study in Honduras.
- Author
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Quirk GJ and Casco L
- Subjects
- Adaptation, Psychological, Adolescent, Adult, Bereavement, Child, Female, Grief, Honduras, Humans, Male, Personality Assessment, Stress Disorders, Post-Traumatic psychology, Developing Countries, Family psychology, Politics, Stress Disorders, Post-Traumatic epidemiology, Torture, Violence
- Abstract
The effect of forced disappearance on the physical and psychological health of family members was assessed by interviews carried out in Honduras. Families of the disappeared were compared with two control groups: (1) families who lost a member due to accident or illness; and (2) families where no one had died within the past 10 years. Constellations of stress-related symptoms commonly seen in post-traumatic stress disorder and other anxiety disorders were approx. 2 times more prevalent in families of the disappeared as compared to the other two groups, indicating that families of the disappeared suffer over and above that due to normal grieving. It is suggested that the atmosphere of fear and isolation experienced by families of the disappeared is a causative factor in the prolongation of stress-related disorders years after the traumatic event.
- Published
- 1994
- Full Text
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33. The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells.
- Author
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Quirk GJ, Muller RU, Kubie JL, and Ranck JB Jr
- Subjects
- Animals, Behavior, Animal physiology, Cues, Electrophysiology methods, Hippocampus cytology, Limbic System cytology, Rats, Television, Hippocampus physiology, Limbic System physiology, Neurons physiology
- Abstract
Hippocampal place cells in the rat are so named because they fire predominantly within circumscribed regions of the environment. This study describes the positional firing properties of cells afferent to hippocampal place cells, in superficial layers of medial entorhinal cortex (MEC). MEC cells in these layers project to the hippocampus via the perforant path and, along with lateral entorhinal cells, are the sole route by which cortical information reaches the hippocampus. MEC cells were recorded from rats while they retrieved pellets in simple geometric enclosures. The behavioral task as well as procedures for data collection and analysis were the same used in previous studies on hippocampal place cells (e.g., Muller et al., 1987) in order to facilitate the direct comparison between hippocampal and entorhinal cells. The firing patterns of MEC cells show pronounced locational variations reminiscent of hippocampal firing fields, but with a lower signal-to-noise ratio. While noisy, MEC firing patterns are stationary in time as evidenced by their reproducibility, and the improvement in spatial signal with long-duration recordings. Furthermore, MEC firing patterns are not due to variations in the rat's behavior. Taken together, these data show that the positional firing variations in MEC cells are due to the location-specificity of MEC cells. These and additional data lead us to conclude that location-specific information exists prior to the hippocampus. MEC cells are similar to hippocampal place cells in that their firing can be controlled by the rotation of a visual cue (a white card attached to the wall), but is not disrupted by removing the cue. An important difference between hippocampal and entorhinal cells was seen when the shape of the recording chamber was changed. In the transition from a cylinder to an equal-area square of similar appearance, MEC firing patterns topologically transformed (or "stretched") while those of hippocampal place cells changed to an unpredictable pattern. We conclude that the positional firing of MEC cells is more "sensory bound" than hippocampal cells, and that the ability to discriminate different environments, while present in the hippocampus, is not yet present in its input from MEC.
- Published
- 1992
34. A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex.
- Author
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Amassian VE, Quirk GJ, and Stewart M
- Subjects
- Action Potentials physiology, Animals, Electroencephalography, Macaca, Reaction Time, Electric Stimulation, Magnetics, Motor Cortex physiology, Pyramidal Tracts physiology
- Abstract
The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred. The site of direct corticospinal excitation by a lateral-sagittally orientated MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly. Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.
- Published
- 1990
- Full Text
- View/download PDF
35. The firing of hippocampal place cells in the dark depends on the rat's recent experience.
- Author
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Quirk GJ, Muller RU, and Kubie JL
- Subjects
- Animals, Cues, Electrophysiology, Hippocampus cytology, Light, Rats, Darkness, Hippocampus physiology, Neurons physiology
- Abstract
Hippocampal "place cells" fire when a freely moving rat is in a given location. The firing of these cells is controlled by visual and nonvisual environmental cues. The effects of darkness on the firing of place cells was studied using the task of Muller et al. (1987), in which rats were trained to chase randomly scattered food pellets in a cylindrical drum with a white cue-card attached to the wall. The position of the rats was tracked via an infrared LED on the headstage with a video system linked to computer. Two experimental protocols were used: in the first, lights were turned off after the rat had already been placed in the chamber; in the second, the rat was placed in the darkened chamber. The dark segments produced by these 2 methods were identical with respect to light and other cues but differed with respect to the rat's experience. The firing patterns of 24 of 28 cells were unaffected by darkness when it was preceded by a light period. In contrast, the firing patterns of 14 of 22 cells changed dramatically when the rats were put into the darkened chamber. Furthermore, the majority of cells that changed their firing pattern in initial darkness maintained that change when the lights were turned on. These results show that place cells can fire differently in identical cue situations and that the best predictor of firing pattern is a combination of current cues and the rat's recent experience. The results are discussed in terms of mnemonic properties of hippocampal cells and "remapping" of place cell representations.
- Published
- 1990
36. Corticospinal responses to electrical stimulation of motor cortex in the rat.
- Author
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Stewart M, Quirk GJ, and Amassian VE
- Subjects
- Action Potentials, Animals, Efferent Pathways physiology, Electric Stimulation, Evoked Potentials, Male, Neural Conduction, Rats, Rats, Inbred Strains, Reaction Time, Motor Cortex physiology, Spinal Cord physiology
- Abstract
Direct and indirect corticospinal responses to electrical stimulation of motor cortex were identified in urethane-anesthetized rats. 'Killed-end' recordings were taken from the corticospinal tract at the level of the cervical cord (C1-C2) and from the medullary pyramid. The identities of direct (D) and indirect (I) corticospinal responses were confirmed by: (1) removing motor cortex to eliminate I activity, and (2) pharmacologically increasing neocortical excitability, prior to any lesions, to increase I activity. Our data indicate that the conduction velocity of the fastest corticospinal fibers is approximately 18 m/s. Our identification of the components of the corticospinal response will permit the interpretation of the more complicated surface or 'non-killed-end' depth recordings which have shown particular utility in evaluating spinal cord damage.
- Published
- 1990
- Full Text
- View/download PDF
37. Separable roles of hippocampal granule cells in forgetting and pyramidal cells in remembering spatial information.
- Author
-
Collier TJ, Quirk GJ, and Routtenberg A
- Subjects
- Animals, Brain Mapping, Electric Stimulation, Hippocampus cytology, Male, Naloxone pharmacology, Rats, Rats, Inbred Strains, Hippocampus physiology, Memory physiology, Space Perception physiology
- Abstract
To investigate the roles individual hippocampal cell groups play in processing of spatial information for memory, we administered low-intensity electrical stimulation to the granule cells, CA3 and CA1 pyramidal cells of the dorsal hippocampus at selected times before and after acquisition of the solution to a radial maze win-stay task. Stimulation of any of the 3 cells populations yielded a variable duration anterograde disruption of memory performance, while stimulation of dentate gyrus granule cells alone produced a declarative memory-specific retrograde amnesia. The amnestic effect of granule cell stimulation was not associated with after discharges in the hippocampus and was prevented by systemic administration of the opiate antagonist naloxone. Our results support the view that this electrical stimulus does not disrupt, but rather, activates the normal function of the granule cell system, resulting in erasure of information held in declarative memory. In contrast, similar activation of the pyramidal cell system does not yield retrograde amnesia, suggesting a normal role for these cells in promoting memory for spatial information.
- Published
- 1987
- Full Text
- View/download PDF
38. Evidence for the lack of interaction between (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine and alpha-adrenoceptors in vivo and in vitro.
- Author
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Cervoni P, Goldstein BM, Herzlinger H, Lai FM, and Quirk GJ
- Subjects
- Angiotensin II pharmacology, Animals, Blood Pressure drug effects, Cats, Epinephrine pharmacology, In Vitro Techniques, Male, Nictitating Membrane drug effects, Norepinephrine pharmacology, Phentolamine pharmacology, Platelet Activating Factor pharmacology, Rats, Rats, Inbred SHR, Receptors, Adrenergic, alpha metabolism, Splanchnic Circulation drug effects, Platelet Activating Factor analogs & derivatives, Receptors, Adrenergic, alpha drug effects
- Abstract
The interactions of (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine (octadecyl-AGPC) with alpha-adrenoceptors were studied in rat mesenteric artery, cat nictitating membrane and on the blood pressure of the cat and spontaneously hypertensive (SH) rat. Using a direct radioligand alpha-adrenoceptor binding assay in particulate fractions of rat mesenteric arteries, octadecyl-AGPC was found to be 5 X 10(7) and 75 times less potent than prazosin and noradrenaline (NA), respectively, in displacing (2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane ([3H]-WB 4101--a selective probe for the identification of alpha-adrenoceptors). In the cat, intravenous infusions of octadecyl-AGPC, which produce a hypotensive response, did not attenuate nictitating membrane contractions in vivo in response to intravenous injections of NA, adrenaline (Ad) or to electrical stimulation of the postganglionic fibres of the superior cervical ganglion. In these experiments, the pressor responses to NA or Ad were not affected by octadecyl-AGPC. Phentolamine, on the other hand, attenuated nictitating membrane contractions and blood pressure responses to Ad or NA. In the SH rat, octadecyl-AGPC decreased mean arterial blood pressure (MABP). After an intravenous dose of phentolamine which lowered MABP, the depressor response to octadecyl-AGPC was reduced. When MABP in the phentolamine-treated SH rat was restored to its initial level with an infusion of angiotensin II (AII), the depressor response to octadecyl-AGPC was restored to its original magnitude. The effectiveness of alpha-adrenoceptor blockade under these experimental conditions was monitored with intravenous NA and Ad. Thus, based on radioligand binding studies and pharmacological studies, it is concluded that octadecyl-AGPC lacks the ability to interact with alpha-adrenoceptors.
- Published
- 1984
- Full Text
- View/download PDF
39. Surgical repositioning of impacted mandibular second molar teeth.
- Author
-
Johnson JV and Quirk GP
- Subjects
- Adolescent, Child, Female, Humans, Male, Mandible, Methods, Molar anatomy & histology, Molar, Third surgery, Molar, Third transplantation, Tooth Extraction, Tooth Root anatomy & histology, Tooth, Impacted etiology, Molar surgery, Tooth, Impacted surgery
- Abstract
Impacted second molars refractory to orthodontic treatment are frequent problems. The family dentist and the orthodontist should be on the alert for them. A philosophy for their management and the authors' experience over the past 13 years are presented. The proper time for definitive treatment of these impactions is during early adolescence, generally in the 11- to 14-year range. Impaction of the second molar is usually a problem of arch length deficiency. There may be an associated problem with a third molar impaction. The alternatives for impacted second molar treatments are surgical repositioning with or without adjacent third molar removal, removal of the second molar allowing the third molar to erupt, and transplantation of the third molar to the second molar socket. In the authors' experience, surgical repositioning has provided the most promising results of the three choices. Technical aspects of surgical repositioning are discussed along with case selection criteria. Six cases are presented to demonstrate typical problems and their management. With proper timing and intervention, the prognosis is excellent for repositioning second molar impactions.
- Published
- 1987
- Full Text
- View/download PDF
40. Antihypertensive activity of dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester (CL 115,347), a new orally and transdermally long-acting antihypertensive agent.
- Author
-
Chan PS, Cervoni P, Ronsberg MA, Accomando RC, Quirk GJ, Scully PA, and Lipchuck LM
- Subjects
- Administration, Oral, Administration, Topical, Animals, Blood Pressure drug effects, Desoxycorticosterone administration & dosage, Dogs, Female, Hypertension, Renal drug therapy, Hypertension, Renal physiopathology, Injections, Intravenous, Macaca mulatta, Male, Rats, Rats, Inbred Strains, Time Factors, Antihypertensive Agents administration & dosage, Dinoprostone analogs & derivatives, Prostaglandins E, Synthetic administration & dosage
- Abstract
CL 115,347 [dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester] has a broad spectrum of antihypertensive activity in many animal hypertension models in every species tested. In conscious spontaneously hypertensive rats, CL 115,347 at 0.25 to 10 mg/kg orally produced 31 to 53 mm Hg lowering of the mean arterial blood pressure (MABP) with a duration of action of 1 to greater than 8 hr. When applied transdermally, CL 115,347 was more potent and longer acting than by the oral route. At 0.03 to 1 mg/kg, topically applied CL 115,347 lowered MABP of spontaneously hypertensive rats 27 to 46 mm Hg. Duration of action was greater than 6 to greater than 24 hr. CL 115,347 was also active in conscious normotensive rats (-27 mm Hg), deoxycorticosterone-salt-induced hypertensive rats (-51 mm Hg) and aorta-coarcted hypertensive rats (-52 mm Hg) when tested at 1 mg/kg orally. At 3 mg/kg orally, CL 115,347 lowered MABP of Dahl "S" salt-sensitive rats 55 mm Hg. CL 115,347 orally and s.c. lowered MABP in two-kidney, one-clip Goldblatt renal hypertensive dogs and was accompanied by tachycardia. CL 115,347, at 0.1 and 0.2 mg/kg orally, maximally lowered the systolic blood pressure of conscious rhesus monkeys 33 to 63 mm Hg with only a slight increase in heart rate. Therefore, CL 115,347 was antihypertensive in animals with low, normal and high plasma renin activity. The present findings suggest that CL 115,347 may be useful for the treatment of human hypertension.
- Published
- 1983
41. The diuretic effects of CL 115,129 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2) and l-prostaglandin E2 in dogs.
- Author
-
Quirk GJ, Chan PS, Cervoni P, and Emma J
- Subjects
- Animals, Dinoprostone, Dogs, Female, Kidney drug effects, Male, Diuresis drug effects, Prostaglandins E pharmacology, Prostaglandins E, Synthetic pharmacology
- Abstract
CL 115,129, the corresponding carboxylic acid and major metabolite of CL 115,347 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester), a potent orally and transdermally long acting antihypertensive agent, infused at 0.1 microgram/kg/min into the left renal artery of sodium pentobarbital anesthetized beagle dogs increased urinary volume, sodium (Na+), potassium (K+) and chloride (Cl-) excretion of the left kidney 289, 201, 101 and 229%, respectively, over the 30 min vehicle-treated control periods. At 0.3 microgram/kg/min CL 115,129 caused a 475 and 336% increase in urinary volume and Na+, respectively. l-Prostaglandin E2 (l-PGE2) infused at 0.1 microgram/kg/min into the left renal artery increased urinary volume, Na+, K+ and Cl- excretion of the left kidney of anesthetized beagle dogs 416, 234, 112 and 255%, respectively, over the control. Both CL 115,129 and l-PGE2 did not affect the systemic arterial blood pressure or the electrolyte excretion of the contralateral kidney. It is concluded that in contrast to other conventional vasodilators, which may cause severe water and electrolyte retention, CL 115,347, via its metabolite CL 115,129, may cause diuresis and natriuresis in many clinical settings when used as an antihypertensive.
- Published
- 1984
- Full Text
- View/download PDF
42. Physiological basis of motor effects of a transient stimulus to cerebral cortex.
- Author
-
Amassian VE, Stewart M, Quirk GJ, and Rosenthal JL
- Subjects
- Animals, Efferent Pathways physiology, Electric Stimulation, Humans, Interneurons physiology, Motor Neurons physiology, Muscles physiology, Reaction Time, Scalp innervation, Evoked Potentials, Motor Cortex physiology, Pyramidal Tracts physiology, Spinal Cord physiology
- Abstract
This contribution includes a selective review of previously published material, findings from some new experiments, and discussion of some relationships between animal and recent human data. The major questions are: What descends from the cerebral cortex after a brief surface stimulus? What explains the various components of the corticofugal discharge? What are the motor consequences of the corticofugal discharge, and what are the effects of lesions on both? The focus is on the corticospinal system, which through its monosynaptic connection with alpha motoneurons of distal muscles accounts for the short latency movements after a transient cortical stimulus. The pyramidal and lateral corticospinal tract response in monkey or cat to a surface stimulus applied to area 4 is a direct (D) wave conducted in fast axons followed by several indirect (I) waves with a period of greater than 1 ms. Although computer summing reveals, at increasing amplitudes, D and I waves in recordings from nuchal skin, vertebra, and surface of the spinal cord, "killed end" recording is essential to reveal the true extent of I relative to D waves. The D wave might result from excitation of: the initial segment (IS), i.e., the classical spike trigger zone; the first or deeper nodes in white matter; or arborizations of the axon collaterals in gray matter. Under different circumstances, each of these modes of excitation can be effective. Thus, with threshold stimulation through separated bipolar electrodes, intracellular recording from pyramidal tract (PT) and uninvaded motor cortical neurons shows that D activation usually occurs when the membrane potential immediately before the stimulus is relatively depolarized, implying excitation of the IS region, i.e., close to the site of synaptic transfer. A monopolar surface (+) stimulus at the appropriate focus usually generates a D wave at weaker intensity than does a surface (-) stimulus. However, if a little above threshold, stimuli of either polarity generate both D and I waves, but the ratio of D:I amplitude is usually greater with surface (+) stimulation. A theoretical estimate of the depth of excitation by a surface (+) stimulus was consistent with threshold excitation occurring at the first node. Slow PT neurons are excited by surface stimulation, but trivially contribute to population PT or corticospinal recordings. Intracellular recording from PT neurons identifies a monosynaptic excitatory postsynaptic potential as the cause of the first I wave, the period between successive I waves reflecting single delays for synaptic discharge.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1987
43. The organization of the rat motor cortex: a microstimulation mapping study.
- Author
-
Neafsey EJ, Bold EL, Haas G, Hurley-Gius KM, Quirk G, Sievert CF, and Terreberry RR
- Subjects
- Animals, Brain Mapping, Electric Stimulation, Forelimb innervation, Hindlimb innervation, Lip innervation, Mandible innervation, Motor Cortex cytology, Rats, Somatosensory Cortex physiology, Tongue innervation, Vibrissae physiology, Motor Cortex physiology
- Abstract
In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.
- Published
- 1986
- Full Text
- View/download PDF
44. HOSPITAL DENTISTRY.
- Author
-
QUIRK GP
- Subjects
- Humans, Dental Service, Hospital, Dentistry, Hospitals
- Published
- 1965
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