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https://www.readbyqxmd.com/read/28912243/thirst-associated-preoptic-neurons-encode-an-aversive-motivational-drive
#1
William E Allen, Laura A DeNardo, Michael Z Chen, Cindy D Liu, Kyle M Loh, Lief E Fenno, Charu Ramakrishnan, Karl Deisseroth, Liqun Luo
Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28912215/the-form-and-function-of-channelrhodopsin
#2
REVIEW
Karl Deisseroth, Peter Hegemann
Channelrhodopsins are light-gated ion channels that, via regulation of flagellar function, enable single-celled motile algae to seek ambient light conditions suitable for photosynthesis and survival. These plant behavioral responses were initially investigated more than 150 years ago. Recently, major principles of function for light-gated ion channels have been elucidated by creating channelrhodopsins with kinetics that are accelerated or slowed over orders of magnitude, by discovering and designing channelrhodopsins with altered spectral properties, by solving the high-resolution channelrhodopsin crystal structure, and by structural model-guided redesign of channelrhodopsins for altered ion selectivity...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28902833/rabies-screen-reveals-gpe-control-of-cocaine-triggered-plasticity
#3
Kevin T Beier, Christina K Kim, Paul Hoerbelt, Lin Wai Hung, Boris D Heifets, Katherine E DeLoach, Timothy J Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C Malenka
Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse...
September 13, 2017: Nature
https://www.readbyqxmd.com/read/28898248/place-field-assembly-distribution-encodes-preferred-locations
#4
Omar Mamad, Lars Stumpp, Harold M McNamara, Charu Ramakrishnan, Karl Deisseroth, Richard B Reilly, Marian Tsanov
The hippocampus is the main locus of episodic memory formation and the neurons there encode the spatial map of the environment. Hippocampal place cells represent location, but their role in the learning of preferential location remains unclear. The hippocampus may encode locations independently from the stimuli and events that are associated with these locations. We have discovered a unique population code for the experience-dependent value of the context. The degree of reward-driven navigation preference highly correlates with the spatial distribution of the place fields recorded in the CA1 region of the hippocampus...
September 12, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28893946/a-radial-axis-defined-by-semaphorin-to-neuropilin-signaling-controls-pancreatic-islet-morphogenesis
#5
Philip T Pauerstein, Krissie Tellez, Kirk B Willmarth, Keon Min Park, Brian Hsueh, H Efsun Arda, Xueying Gu, Haig Aghajanian, Karl Deisseroth, Jonathan A Epstein, Seung K Kim
The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, endocrine progenitors delaminate, migrate radially, and cluster to form islets. Despite the distinctive distribution of islets, spatially localized signals that control islet morphogenesis have not been discovered. Here we identify a radial signaling axis that instructs developing islet cells to disperse throughout the pancreas. A screen of pancreatic extracellular signals identified factors that stimulated islet cell development...
September 11, 2017: Development
https://www.readbyqxmd.com/read/28817803/developmental-dysfunction-of-vip-interneurons-impairs-cortical-circuits
#6
Renata Batista-Brito, Martin Vinck, Katie A Ferguson, Jeremy T Chang, David Laubender, Gyorgy Lur, James M Mossner, Victoria G Hernandez, Charu Ramakrishnan, Karl Deisseroth, Michael J Higley, Jessica A Cardin
GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state dependence...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28768803/modulation-of-prefrontal-cortex-excitation-inhibition-balance-rescues-social-behavior-in-cntnap2-deficient-mice
#7
Aslihan Selimbeyoglu, Christina K Kim, Masatoshi Inoue, Soo Yeun Lee, Alice S O Hong, Isaac Kauvar, Charu Ramakrishnan, Lief E Fenno, Thomas J Davidson, Matthew Wright, Karl Deisseroth
Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated in the neural circuit activity-based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I balance in mouse brain could correct deficits in social behavior. We used mice lacking the CNTNAP2 gene, which has been implicated in autism, and achieved a temporally precise reduction in E:I balance in the medial prefrontal cortex (mPFC) either by optogenetically increasing the excitability of inhibitory parvalbumin (PV) neurons or decreasing the excitability of excitatory pyramidal neurons...
August 2, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724969/pathways-to-clinical-clarity-volumetric-analysis-of-irregular-soft-and-heterogeneous-tissues-in-development-and-disease
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
August 1, 2017: NeuroImage
https://www.readbyqxmd.com/read/28390647/brain-derived-neurotrophic-factor-in-the-mesolimbic-reward-circuitry-mediates-nociception-in-chronic-neuropathic-pain
#18
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
#19
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
#20
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
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