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  • 1
    Publication Date: 2011-03-11
    Description: Anxiety--a sustained state of heightened apprehension in the absence of immediate threat--becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)--achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA--exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154022/" 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/PMC3154022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tye, Kay M -- Prakash, Rohit -- Kim, Sung-Yon -- Fenno, Lief E -- Grosenick, Logan -- Zarabi, Hosniya -- Thompson, Kimberly R -- Gradinaru, Viviana -- Ramakrishnan, Charu -- Deisseroth, Karl -- 1F32MH088010-01/MH/NIMH NIH HHS/ -- DP1 OD000616/OD/NIH HHS/ -- DP1 OD000616-01/OD/NIH HHS/ -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 DA020794-01/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH075957-01A2/MH/NIMH NIH HHS/ -- England -- Nature. 2011 Mar 17;471(7338):358-62. doi: 10.1038/nature09820. Epub 2011 Mar 9.〈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/21389985" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology/radiation effects ; Animals ; Anxiety/*physiopathology ; Anxiety Disorders/physiopathology ; Halorhodopsins/metabolism ; Light ; Mice ; Models, Neurological ; Neural Pathways/physiology/radiation effects ; Neurons/physiology/radiation effects ; Stress, Physiological/physiology ; Synapses/physiology/radiation effects
    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: 2012-07-31
    Description: Adult neurogenesis arises from neural stem cells within specialized niches. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem cells (RGLs) respond tonically to the neurotransmitter gamma-aminobutyric acid (GABA) by means of gamma2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of gamma2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a niche cell-signal-receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem cells in response to neuronal activity and experience.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438284/" 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/PMC3438284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Juan -- Zhong, Chun -- Bonaguidi, Michael A -- Sun, Gerald J -- Hsu, Derek -- Gu, Yan -- Meletis, Konstantinos -- Huang, Z Josh -- Ge, Shaoyu -- Enikolopov, Grigori -- Deisseroth, Karl -- Luscher, Bernhard -- Christian, Kimberly M -- Ming, Guo-li -- Song, Hongjun -- AG040209/AG/NIA NIH HHS/ -- HD069184/HD/NICHD NIH HHS/ -- MH089111/MH/NIMH NIH HHS/ -- NS048271/NS/NINDS NIH HHS/ -- R01 AG040209/AG/NIA NIH HHS/ -- R01 HD069184/HD/NICHD NIH HHS/ -- R01 NS047344/NS/NINDS NIH HHS/ -- R01 NS048271/NS/NINDS NIH HHS/ -- R01 NS065915/NS/NINDS NIH HHS/ -- R21 ES021957/ES/NIEHS NIH HHS/ -- R56 NS047344/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):150-4. doi: 10.1038/nature11306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22842902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage/drug effects ; Cell Proliferation/drug effects ; Dentate Gyrus/cytology/drug effects/metabolism ; Female ; GABA Modulators/pharmacology ; GABA-A Receptor Agonists/pharmacology ; GABA-A Receptor Antagonists/pharmacology ; Interneurons/cytology/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/drug effects/*physiology ; Neural Stem Cells/*cytology/drug effects/metabolism ; *Neurogenesis/drug effects ; Neuroglia/cytology/drug effects/metabolism ; Parvalbumins/metabolism ; Receptors, GABA-A/metabolism ; Signal Transduction/drug effects ; Somatostatin/metabolism ; Stem Cell Niche/drug effects/physiology ; Vasoactive Intestinal Peptide/metabolism ; gamma-Aminobutyric Acid/metabolism
    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: 2012-08-11
    Description: Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (gamma-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIalpha (CAMKIIalpha)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422431/" 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/PMC3422431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Seung-Hee -- Kwan, Alex C -- Zhang, Siyu -- Phoumthipphavong, Victoria -- Flannery, John G -- Masmanidis, Sotiris C -- Taniguchi, Hiroki -- Huang, Z Josh -- Zhang, Feng -- Boyden, Edward S -- Deisseroth, Karl -- Dan, Yang -- PN2 EY018241/EY/NEI NIH HHS/ -- R01 EY018861/EY/NEI NIH HHS/ -- R01 NS067199/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Aug 16;488(7411):379-83. doi: 10.1038/nature11312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878719" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/deficiency/genetics/metabolism ; Discrimination Learning ; Interneurons/*physiology ; Mice ; Models, Neurological ; Neural Inhibition/physiology ; Parvalbumins/metabolism ; Rhodopsin/metabolism ; Rhodopsins, Microbial/metabolism ; Visual Cortex/*cytology/*physiology ; Visual Perception/*physiology ; Wakefulness/physiology ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    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
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-12-14
    Description: Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160519/" 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/PMC4160519/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tye, Kay M -- Mirzabekov, Julie J -- Warden, Melissa R -- Ferenczi, Emily A -- Tsai, Hsing-Chen -- Finkelstein, Joel -- Kim, Sung-Yon -- Adhikari, Avishek -- Thompson, Kimberly R -- Andalman, Aaron S -- Gunaydin, Lisa A -- Witten, Ilana B -- Deisseroth, Karl -- DP2 DA035149/DA/NIDA NIH HHS/ -- F32 MH880102/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 24;493(7433):537-41. doi: 10.1038/nature11740. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. kaytye@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235822" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Depression/chemically induced/*physiopathology ; Dopamine/metabolism ; Dopaminergic Neurons/drug effects/*metabolism/radiation effects ; Female ; Male ; Mice ; Models, Neurological ; Nucleus Accumbens/metabolism ; Optogenetics ; Phenotype ; Rats ; Rats, Long-Evans ; Stress, Psychological/physiopathology ; Time Factors ; Ventral Tegmental Area/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-01-17
    Description: The recent development of technologies for investigating specific components of intact biological systems has allowed elucidation of the neural circuitry underlying adaptive and maladaptive behaviours. Investigators are now able to observe and control, with high spatio-temporal resolution, structurally defined intact pathways along which electrical activity flows during and after the performance of complex behaviours. These investigations have revealed that control of projection-specific dynamics is well suited to modulating behavioural patterns that are relevant to a broad range of psychiatric diseases. Structural dynamics principles have emerged to provide diverse, unexpected and causal insights into the operation of intact and diseased nervous systems, linking form and function in the brain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069282/" 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/PMC4069282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- R01 MH099647/MH/NIMH NIH HHS/ -- R37 DA035377/DA/NIDA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 16;505(7483):309-17. doi: 10.1038/nature12982.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Bioengineering, Stanford University, Stanford, California 94305, USA. [2] Department of Psychiatry, Stanford University, Stanford, California 94305, USA. [3] 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/24429629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior/*physiology ; Deep Brain Stimulation ; Depressive Disorder/pathology/physiopathology ; *Health ; Humans ; Mental Disorders/*pathology/*physiopathology ; *Neural Pathways
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-10-06
    Description: Top-down prefrontal cortex inputs to the hippocampus have been hypothesized to be important in memory consolidation, retrieval, and the pathophysiology of major psychiatric diseases; however, no such direct projections have been identified and functionally described. Here we report the discovery of a monosynaptic prefrontal cortex (predominantly anterior cingulate) to hippocampus (CA3 to CA1 region) projection in mice, and find that optogenetic manipulation of this projection (here termed AC-CA) is capable of eliciting contextual memory retrieval. To explore the network mechanisms of this process, we developed and applied tools to observe cellular-resolution neural activity in the hippocampus while stimulating AC-CA projections during memory retrieval in mice behaving in virtual-reality environments. Using this approach, we found that learning drives the emergence of a sparse class of neurons in CA2/CA3 that are highly correlated with the local network and that lead synchronous population activity events; these neurons are then preferentially recruited by the AC-CA projection during memory retrieval. These findings reveal a sparsely implemented memory retrieval mechanism in the hippocampus that operates via direct top-down prefrontal input, with implications for the patterning and storage of salient memory representations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rajasethupathy, Priyamvada -- Sankaran, Sethuraman -- Marshel, James H -- Kim, Christina K -- Ferenczi, Emily -- Lee, Soo Yeun -- Berndt, Andre -- Ramakrishnan, Charu -- Jaffe, Anna -- Lo, Maisie -- Liston, Conor -- Deisseroth, Karl -- R00 MH097822/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Oct 29;526(7575):653-9. doi: 10.1038/nature15389. Epub 2015 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA. ; CNC Program, Stanford University, Stanford, California 94305, USA. ; Neuroscience 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/26436451" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    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
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-04-26
    Description: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" 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/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; CA1 Region, Hippocampal/cytology ; CA3 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neurons/*physiology ; Optogenetics ; Patch-Clamp Techniques ; Protein Engineering ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/*chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2011-07-29
    Description: Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155501/" 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/PMC4155501/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yizhar, Ofer -- Fenno, Lief E -- Prigge, Matthias -- Schneider, Franziska -- Davidson, Thomas J -- O'Shea, Daniel J -- Sohal, Vikaas S -- Goshen, Inbal -- Finkelstein, Joel -- Paz, Jeanne T -- Stehfest, Katja -- Fudim, Roman -- Ramakrishnan, Charu -- Huguenard, John R -- Hegemann, Peter -- Deisseroth, Karl -- DP1 OD000616/OD/NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- R01 NS006477/NS/NINDS NIH HHS/ -- R01 NS034774/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 27;477(7363):171-8. doi: 10.1038/nature10360.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California, USA. ofer.yizhar@weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21796121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/physiopathology ; Disease Models, Animal ; HEK293 Cells ; Hippocampus/cytology ; Humans ; Learning ; Mental Disorders/physiopathology ; Mice ; *Models, Neurological ; Motor Activity ; Neural Inhibition/*physiology ; Neurons/*metabolism ; Opsins/metabolism ; Prefrontal Cortex/*physiology/*physiopathology ; Schizophrenia/physiopathology ; *Social Behavior
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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