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  • Mice, Inbred C57BL  (3)
  • Nature Publishing Group (NPG)  (3)
  • American Geophysical Union (AGU)
  • American Institute of Physics
  • American Institute of Physics (AIP)
  • National Academy of Sciences
  • Oxford University Press
  • 2015-2019  (3)
Collection
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  • Nature Publishing Group (NPG)  (3)
  • American Geophysical Union (AGU)
  • American Institute of Physics
  • American Institute of Physics (AIP)
  • National Academy of Sciences
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Year
  • 1
    Publication Date: 2015-11-05
    Description: Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adhikari, Avishek -- Lerner, Talia N -- Finkelstein, Joel -- Pak, Sally -- Jennings, Joshua H -- Davidson, Thomas J -- Ferenczi, Emily -- Gunaydin, Lisa A -- Mirzabekov, Julie J -- Ye, Li -- Kim, Sung-Yon -- Lei, Anna -- Deisseroth, Karl -- 1F32MH105053-01/MH/NIMH NIH HHS/ -- K99 MH106649/MH/NIMH NIH HHS/ -- K99MH106649/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Nov 12;527(7577):179-85. doi: 10.1038/nature15698. Epub 2015 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA. ; CNC Program, Stanford University, Stanford, California 94304, USA. ; Neurosciences Program, Stanford University, Stanford, California 94305, USA. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA. ; Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26536109" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology ; Animals ; Anxiety/*physiopathology/psychology ; Extinction, Psychological/physiology ; Fear/*physiology/psychology ; Female ; Freezing Reaction, Cataleptic/physiology ; Learning/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/*physiology ; Prefrontal Cortex/cytology/physiology ; Stress, Psychological/physiopathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-06-02
    Description: One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506234/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Louveau, Antoine -- Smirnov, Igor -- Keyes, Timothy J -- Eccles, Jacob D -- Rouhani, Sherin J -- Peske, J David -- Derecki, Noel C -- Castle, David -- Mandell, James W -- Lee, Kevin S -- Harris, Tajie H -- Kipnis, Jonathan -- P30 CA044579/CA/NCI NIH HHS/ -- R01 AG034113/AG/NIA NIH HHS/ -- R01 NS061973/NS/NINDS NIH HHS/ -- R01AG034113/AG/NIA NIH HHS/ -- R01NS061973/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Medicine (Division of Allergy), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Pathology (Neuropathology), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26030524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/*anatomy & histology/cytology/*immunology ; Cranial Sinuses/anatomy & histology ; Female ; Humans ; Immune Tolerance/immunology ; Immunologic Surveillance/immunology ; Lymphatic Vessels/*anatomy & histology/cytology/*immunology ; Male ; Meninges/anatomy & histology/cytology/immunology ; Mice, Inbred C57BL ; T-Lymphocytes/cytology/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-03-26
    Description: Congenital heart disease (CHD) is the most prevalent birth defect, affecting nearly 1% of live births; the incidence of CHD is up to tenfold higher in human fetuses. A genetic contribution is strongly suggested by the association of CHD with chromosome abnormalities and high recurrence risk. Here we report findings from a recessive forward genetic screen in fetal mice, showing that cilia and cilia-transduced cell signalling have important roles in the pathogenesis of CHD. The cilium is an evolutionarily conserved organelle projecting from the cell surface with essential roles in diverse cellular processes. Using echocardiography, we ultrasound scanned 87,355 chemically mutagenized C57BL/6J fetal mice and recovered 218 CHD mouse models. Whole-exome sequencing identified 91 recessive CHD mutations in 61 genes. This included 34 cilia-related genes, 16 genes involved in cilia-transduced cell signalling, and 10 genes regulating vesicular trafficking, a pathway important for ciliogenesis and cell signalling. Surprisingly, many CHD genes encoded interacting proteins, suggesting that an interactome protein network may provide a larger genomic context for CHD pathogenesis. These findings provide novel insights into the potential Mendelian genetic contribution to CHD in the fetal population, a segment of the human population not well studied. We note that the pathways identified show overlap with CHD candidate genes recovered in CHD patients, suggesting that they may have relevance to the more complex genetics of CHD overall. These CHD mouse models and 〉8,000 incidental mutations have been sperm archived, creating a rich public resource for human disease modelling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617540/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617540/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, You -- Klena, Nikolai T -- Gabriel, George C -- Liu, Xiaoqin -- Kim, Andrew J -- Lemke, Kristi -- Chen, Yu -- Chatterjee, Bishwanath -- Devine, William -- Damerla, Rama Rao -- Chang, Chienfu -- Yagi, Hisato -- San Agustin, Jovenal T -- Thahir, Mohamed -- Anderton, Shane -- Lawhead, Caroline -- Vescovi, Anita -- Pratt, Herbert -- Morgan, Judy -- Haynes, Leslie -- Smith, Cynthia L -- Eppig, Janan T -- Reinholdt, Laura -- Francis, Richard -- Leatherbury, Linda -- Ganapathiraju, Madhavi K -- Tobita, Kimimasa -- Pazour, Gregory J -- Lo, Cecilia W -- HG000330/HG/NHGRI NIH HHS/ -- R01 GM060992/GM/NIGMS NIH HHS/ -- R01MH094564/MH/NIMH NIH HHS/ -- U01 HL098180/HL/NHLBI NIH HHS/ -- U01HL098180/HL/NHLBI NIH HHS/ -- U01HL098188/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 May 28;521(7553):520-4. doi: 10.1038/nature14269. Epub 2015 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA. ; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; 1] Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15206, USA [2] Intelligent Systems Program, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 16260, USA. ; The Jackson Laboratory, Bar Harbor, Maine 04609, USA. ; The Heart Center, Children's National Medical Center, Washington DC 20010, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25807483" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cilia/genetics/*pathology/physiology/ultrasonography ; DNA Mutational Analysis ; Electrocardiography ; Exome/genetics ; Genes, Recessive ; Genetic Testing ; Heart Defects, Congenital/*genetics/*pathology/ultrasonography ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mutation/genetics ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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