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  • Amygdala/cytology/*physiology  (1)
  • Cross-Linking Reagents/chemistry  (1)
  • Nature Publishing Group (NPG)  (2)
  • 1
    Publication Date: 2013-04-12
    Description: Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092167/" 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/PMC4092167/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Kwanghun -- Wallace, Jenelle -- Kim, Sung-Yon -- Kalyanasundaram, Sandhiya -- Andalman, Aaron S -- Davidson, Thomas J -- Mirzabekov, Julie J -- Zalocusky, Kelly A -- Mattis, Joanna -- Denisin, Aleksandra K -- Pak, Sally -- Bernstein, Hannah -- Ramakrishnan, Charu -- Grosenick, Logan -- Gradinaru, Viviana -- Deisseroth, Karl -- DP1 OD000616/OD/NIH HHS/ -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH099647/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 May 16;497(7449):332-7. doi: 10.1038/nature12107. Epub 2013 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23575631" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*anatomy & histology ; Cross-Linking Reagents/chemistry ; Formaldehyde/chemistry ; Humans ; Hydrogel/chemistry ; Imaging, Three-Dimensional/*methods ; In Situ Hybridization/methods ; Lipids/isolation & purification ; Mice ; Molecular Imaging/*methods ; Permeability ; Phenotype ; Scattering, Radiation
    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: 2015-11-05
    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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