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https://www.readbyqxmd.com/read/28724969/pathways-to-clinical-clarity-volumetric-analysis-of-irregular-soft-and-heterogeneous-tissues-in-development-and-disease
#1
Brian Hsueh, Vanessa M Burns, Philip Pauerstein, Katherine Holzem, Li Ye, Kristin Engberg, Ai-Chi Wang, Xueying Gu, Harini Chakravarthy, H Efsun Arda, Gregory Charville, Hannes Vogel, Igor R Efimov, Seung Kim, Karl Deisseroth
Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678399/a-guide-to-creating-and-testing-new-intrsect-constructs
#2
Lief E Fenno, Joanna Mattis, Charu Ramakrishnan, Karl Deisseroth
As the power of genetically encoded interventional and observational tools for neuroscience expands, the boundaries of experimental design are increasingly defined by limits in selectively expressing these tools in relevant cell types. Single-recombinase-dependent expression systems have been widely used as a means to restrict gene expression based on single features by combining recombinase-dependent viruses with recombinase-expressing transgenic animals. This protocol details how to create INTRSECT constructs and use multiple recombinases to achieve targeting of a desired gene to subsets of neurons that are defined by multiple genetic and/or topological features...
July 5, 2017: Current Protocols in Neuroscience
https://www.readbyqxmd.com/read/28630894/next-generation-probes-particles-and-proteins-for-neural-interfacing
#3
REVIEW
Jonathan Rivnay, Huiliang Wang, Lief Fenno, Karl Deisseroth, George G Malliaras
Bidirectional interfacing with the nervous system enables neuroscience research, diagnosis, and therapy. This two-way communication allows us to monitor the state of the brain and its composite networks and cells as well as to influence them to treat disease or repair/restore sensory or motor function. To provide the most stable and effective interface, the tools of the trade must bridge the soft, ion-rich, and evolving nature of neural tissue with the largely rigid, static realm of microelectronics and medical instruments that allow for readout, analysis, and/or control...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28591583/distinct-thalamic-reticular-cell-types-differentially-modulate-normal-and-pathological-cortical-rhythms
#4
Alexandra Clemente-Perez, Stefanie Ritter Makinson, Bryan Higashikubo, Scott Brovarney, Frances S Cho, Alexander Urry, Stephanie S Holden, Matthew Wimer, Csaba Dávid, Lief E Fenno, László Acsády, Karl Deisseroth, Jeanne T Paz
Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28589967/in-vivo-fiber-photometry-reveals-signature-of-future-stress-susceptibility-in-nucleus-accumbens
#5
Jessie Muir, Zachary S Lorsch, Charu Ramakrishnan, Karl Deisseroth, Eric J Nestler, Erin S Calipari, Rosemary C Bagot
Recognizing why chronic stress causes only a subset of individuals to become depressed is critical to understanding depression on a basic level and, also, to developing treatments that increase resilience. Stress-induced alterations in the activity of reward-related brain regions, such as the nucleus accumbens (NAc), are linked to the pathophysiology of depression. However, it has been difficult to determine if differences in stress susceptibility are pre-existing or merely an effect of chronic stress. The NAc consists largely of medium spiny neurons (MSNs), distinguished by their predominant expression of either D1 or D2 dopamine receptors...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28566522/understanding-the-brain-in-health-and-disease-an-interview-with-karl-deisseroth-professor-of-bioengineering-and-psychiatry-at-stanford-university
#6
Esther Schnapp, Holger Breithaupt
No abstract text is available yet for this article.
June 2017: EMBO Reports
https://www.readbyqxmd.com/read/28566521/optical-and-chemical-discoveries-recognized-for-impact-on-biology-and-psychiatry
#7
Karl Deisseroth
No abstract text is available yet for this article.
June 2017: EMBO Reports
https://www.readbyqxmd.com/read/28521139/global-representations-of-goal-directed-behavior-in-distinct-cell-types-of-mouse-neocortex
#8
William E Allen, Isaac V Kauvar, Michael Z Chen, Ethan B Richman, Samuel J Yang, Ken Chan, Viviana Gradinaru, Benjamin E Deverman, Liqun Luo, Karl Deisseroth
The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca(2+) imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28461701/activation-of-a-novel-p70-s6-kinase-1-dependent-intracellular-cascade-in-the-basolateral-nucleus-of-the-amygdala-is-required-for-the-acquisition-of-extinction-memory
#9
T N Huynh, E Santini, E Mojica, A E Fink, B S Hall, R N Fetcho, L Grosenick, K Deisseroth, J E LeDoux, C Liston, E Klann
Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28411157/the-separate-effects-of-lipids-and-proteins-on-brain-mri-contrast-revealed-through-tissue-clearing
#10
Christoph Leuze, Markus Aswendt, Emily Ferenczi, Corey W Liu, Brian Hsueh, Maged Goubran, Qiyuan Tian, Gary Steinberg, Michael M Zeineh, Karl Deisseroth, Jennifer A McNab
Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY...
April 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28390647/brain-derived-neurotrophic-factor-in-the-mesolimbic-reward-circuitry-mediates-nociception-in-chronic-neuropathic-pain
#11
Hongxing Zhang, Yi-Ling Qian, Chen Li, Di Liu, Lei Wang, Xiao-Yi Wang, Mei-Jun Liu, He Liu, Song Zhang, Xiao-Yun Guo, Jun-Xia Yang, Hai-Lei Ding, Ja Wook Koo, Ezekiell Mouzon, Karl Deisseroth, Eric J Nestler, Venetia Zachariou, Ming-Hu Han, Jun-Li Cao
BACKGROUND: The mesolimbic reward system plays a critical role in modulating nociception; however, its underlying molecular, cellular, and neural circuitry mechanisms remain unknown. METHODS: Chronic constrictive injury (CCI) of the sciatic nerve was used to model neuropathic pain. Projection-specific in vitro recordings in mouse brain slices and in vivo recordings from anesthetized animals were used to measure firing of dopaminergic neurons in the ventral tegmental area (VTA)...
March 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28333125/clarity-reveals-dynamics-of-ovarian-follicular-architecture-and-vasculature-in-three-dimensions
#12
Yi Feng, Peng Cui, Xiaowei Lu, Brian Hsueh, Fredrik Möller Billig, Livia Zarnescu Yanez, Raju Tomer, Derek Boerboom, Peter Carmeliet, Karl Deisseroth, Aaron J W Hsueh
Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303019/integration-of-optogenetics-with-complementary-methodologies-in-systems-neuroscience
#13
REVIEW
Christina K Kim, Avishek Adhikari, Karl Deisseroth
Modern optogenetics can be tuned to evoke activity that corresponds to naturally occurring local or global activity in timing, magnitude or individual-cell patterning. This outcome has been facilitated not only by the development of core features of optogenetics over the past 10 years (microbial-opsin variants, opsin-targeting strategies and light-targeting devices) but also by the recent integration of optogenetics with complementary technologies, spanning electrophysiology, activity imaging and anatomical methods for structural and molecular analysis...
March 17, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28249893/fda-drug-approval-elotuzumab-in-combination-with-lenalidomide-and-dexamethasone-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#14
Nicole J Gormley, Chia-Wen Ko, Albert Deisseroth, Lei Nie, Edvardas Kaminskas, Natasha Kormanik, Kirsten B Goldberg, Ann T Farrell, Richard Pazdur
On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved elotuzumab (Empliciti, Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on results of a phase 3, randomized, open-label, multicenter trial, CA204004, that evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld), compared with lenalidomide and dexamethasone (Ld) alone, in patients with relapsed or refractory multiple myeloma...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28162807/a-brainstem-spinal-cord-inhibitory-circuit-for-mechanical-pain-modulation-by-gaba-and-enkephalins
#15
Amaury François, Sarah A Low, Elizabeth I Sypek, Amelia J Christensen, Chaudy Sotoudeh, Kevin T Beier, Charu Ramakrishnan, Kimberly D Ritola, Reza Sharif-Naeini, Karl Deisseroth, Scott L Delp, Robert C Malenka, Liqun Luo, Adam W Hantman, Grégory Scherrer
Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28146476/cognitive-neuroscience-in-search-of-lost-time
#16
COMMENT
Noah P Young, Karl Deisseroth
No abstract text is available yet for this article.
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28146472/gamma-oscillations-organize-top-down-signalling-to-hypothalamus-and-enable-food-seeking
#17
Marta Carus-Cadavieco, Maria Gorbati, Li Ye, Franziska Bender, Suzanne van der Veldt, Christin Kosse, Christoph Börgers, Soo Yeun Lee, Charu Ramakrishnan, Yubin Hu, Natalia Denisova, Franziska Ramm, Emmanouela Volitaki, Denis Burdakov, Karl Deisseroth, Alexey Ponomarenko, Tatiana Korotkova
Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#18
Erin S Calipari, Barbara Juarez, Carole Morel, Deena M Walker, Michael E Cahill, Efrain Ribeiro, Ciorana Roman-Ortiz, Charu Ramakrishnan, Karl Deisseroth, Ming-Hu Han, Eric J Nestler
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/27991900/molecular-interrogation-of-hypothalamic-organization-reveals-distinct-dopamine-neuronal-subtypes
#19
Roman A Romanov, Amit Zeisel, Joanne Bakker, Fatima Girach, Arash Hellysaz, Raju Tomer, Alán Alpár, Jan Mulder, Frédéric Clotman, Erik Keimpema, Brian Hsueh, Ailey K Crow, Henrik Martens, Christian Schwindling, Daniela Calvigioni, Jaideep S Bains, Zoltán Máté, Gábor Szabó, Yuchio Yanagawa, Ming-Dong Zhang, Andre Rendeiro, Matthias Farlik, Mathias Uhlén, Peer Wulff, Christoph Bock, Christian Broberger, Karl Deisseroth, Tomas Hökfelt, Sten Linnarsson, Tamas L Horvath, Tibor Harkany
The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching...
February 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/27990451/patterned-photostimulation-via-visible-wavelength-photonic-probes-for-deep-brain-optogenetics
#20
Eran Segev, Jacob Reimer, Laurent C Moreaux, Trevor M Fowler, Derrick Chi, Wesley D Sacher, Maisie Lo, Karl Deisseroth, Andreas S Tolias, Andrei Faraon, Michael L Roukes
Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination patterns deep within brain tissue...
January 2017: Neurophotonics
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