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https://www.readbyqxmd.com/read/28333125/clarity-reveals-dynamics-of-ovarian-follicular-architecture-and-vasculature-in-three-dimensions
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27989462/bidirectional-control-of-generalized-epilepsy-networks-via-rapid-real-time-switching-of-firing-mode
#10
Jordan M Sorokin, Thomas J Davidson, Eric Frechette, Armen M Abramian, Karl Deisseroth, John R Huguenard, Jeanne T Paz
Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population of relay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent in vivo studies in anesthetized animals have questioned this simple model...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/27896970/empowering-multi-cohort-gene-expression-analysis-to-increase-reproducibility
#11
Winston A Haynes, Francesco Vallania, Charles Liu, Erika Bongen, Aurelie Tomczak, Marta Andres-Terrè, Shane Lofgren, Andrew Tam, Cole A Deisseroth, Matthew D Li, Timothy E Sweeney, Purvesh Khatri
A major contributor to the scientific reproducibility crisis has been that the results from homogeneous, single-center studies do not generalize to heterogeneous, real world populations. Multi-cohort gene expression analysis has helped to increase reproducibility by aggregating data from diverse populations into a single analysis. To make the multi-cohort analysis process more feasible, we have assembled an analysis pipeline which implements rigorously studied meta-analysis best practices. We have compiled and made publicly available the results of our own multi-cohort gene expression analysis of 103 diseases, spanning 615 studies and 36,915 samples, through a novel and interactive web application...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27806306/in%C3%A2-vivo-interrogation-of-spinal-mechanosensory-circuits
#12
Amelia J Christensen, Shrivats M Iyer, Amaury François, Saurabh Vyas, Charu Ramakrishnan, Sam Vesuna, Karl Deisseroth, Grégory Scherrer, Scott L Delp
Spinal dorsal horn circuits receive, process, and transmit somatosensory information. To understand how specific components of these circuits contribute to behavior, it is critical to be able to directly modulate their activity in unanesthetized in vivo conditions. Here, we develop experimental tools that enable optogenetic control of spinal circuitry in freely moving mice using commonly available materials. We use these tools to examine mechanosensory processing in the spinal cord and observe that optogenetic activation of somatostatin-positive interneurons facilitates both mechanosensory and itch-related behavior, while reversible chemogenetic inhibition of these neurons suppresses mechanosensation...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27798589/a-look-inside-the-brain
#13
Karl Deisseroth
No abstract text is available yet for this article.
September 20, 2016: Scientific American
https://www.readbyqxmd.com/read/27630545/sustained-attentional-states-require-distinct-temporal-involvement-of-the-dorsal-and-ventral-medial-prefrontal-cortex
#14
Antonio Luchicchi, Ouissame Mnie-Filali, Huub Terra, Bastiaan Bruinsma, Sybren F de Kloet, Joshua Obermayer, Tim S Heistek, Roel de Haan, Christiaan P J de Kock, Karl Deisseroth, Tommy Pattij, Huibert D Mansvelder
Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27602521/locus-coeruleus-and-dopaminergic-consolidation-of-everyday-memory
#15
Tomonori Takeuchi, Adrian J Duszkiewicz, Alex Sonneborn, Patrick A Spooner, Miwako Yamasaki, Masahiko Watanabe, Caroline C Smith, Guillén Fernández, Karl Deisseroth, Robert W Greene, Richard G M Morris
The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH(+)) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH(+) neurons project more profusely than ventral tegmental area TH(+) neurons to the hippocampus, optogenetic activation of locus coeruleus TH(+) neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation...
September 15, 2016: Nature
https://www.readbyqxmd.com/read/27579481/molecular-and-cellular-mechanisms-for-trapping-and-activating-emotional-memories
#16
Thomas Rogerson, Balaji Jayaprakash, Denise J Cai, Yoshitake Sano, Yong-Seok Lee, Yu Zhou, Pallavi Bekal, Karl Deisseroth, Alcino J Silva
Recent findings suggest that memory allocation to specific neurons (i.e., neuronal allocation) in the amygdala is not random, but rather the transcription factor cAMP-response element binding protein (CREB) modulates this process, perhaps by regulating the transcription of channels that control neuronal excitability. Here, optogenetic studies in the mouse lateral amygdala (LA) were used to demonstrate that CREB and neuronal excitability regulate which neurons encode an emotional memory. To test the role of CREB in memory allocation, we overexpressed CREB in the lateral amygdala to recruit the encoding of an auditory-fear conditioning (AFC) memory to a subset of neurons...
2016: PloS One
https://www.readbyqxmd.com/read/27568569/pontomesencephalic-tegmental-afferents-to-vta-non-dopamine-neurons-are-necessary-for-appetitive-pavlovian-learning
#17
Hau-Jie Yau, Dong V Wang, Jen-Hui Tsou, Yi-Fang Chuang, Billy T Chen, Karl Deisseroth, Satoshi Ikemoto, Antonello Bonci
The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning. We show that photoinhibition of PPTg-to-VTA cholinergic or glutamatergic inputs during cue presentation dampens the development of anticipatory approach responding to the food receptacle during the cue...
September 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27556938/serotonin-engages-an-anxiety-and-fear-promoting-circuit-in-the-extended-amygdala
#18
Catherine A Marcinkiewcz, Christopher M Mazzone, Giuseppe D'Agostino, Lindsay R Halladay, J Andrew Hardaway, Jeffrey F DiBerto, Montserrat Navarro, Nathan Burnham, Claudia Cristiano, Cayce E Dorrier, Gregory J Tipton, Charu Ramakrishnan, Tamas Kozicz, Karl Deisseroth, Todd E Thiele, Zoe A McElligott, Andrew Holmes, Lora K Heisler, Thomas L Kash
Serotonin (also known as 5-hydroxytryptamine (5-HT)) is a neurotransmitter that has an essential role in the regulation of emotion. However, the precise circuits have not yet been defined through which aversive states are orchestrated by 5-HT. Here we show that 5-HT from the dorsal raphe nucleus (5-HT(DRN)) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRF(BNST)) in mice. Specifically, 5-HT(DRN) projections to the BNST, via actions at 5-HT2C receptors (5-HT2CRs), engage a CRF(BNST) inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus...
September 1, 2016: Nature
https://www.readbyqxmd.com/read/27517089/lsps-optogenetics-to-improve-synaptic-connectivity-mapping-unmasking-the-role-of-basket-cell-mediated-feedforward-inhibition
#19
Julia Brill, Joanna Mattis, Karl Deisseroth, John R Huguenard
Neocortical pyramidal cells (PYRs) receive synaptic inputs from many types of GABAergic interneurons. Connections between parvalbumin (PV)-positive, fast-spiking interneurons ("PV cells") and PYRs are characterized by perisomatic synapses and high-amplitude, short-latency IPSCs. Here, we present novel methods to study the functional influence of PV cells on layer 5 PYRs using optogenetics combined with laser-scanning photostimulation (LSPS). First, we examined the strength and spatial distribution of PV-to-PYR inputs...
July 2016: ENeuro
https://www.readbyqxmd.com/read/27515791/coordination-of-brain-wide-activity-dynamics-by-dopaminergic-neurons
#20
Heather K Decot, Vijay M K Namboodiri, Wei Gao, Jenna A McHenry, Joshua H Jennings, Sung-Ho Lee, Pranish A Kantak, Yu-Chieh Jill Kao, Manasmita Das, Ilana B Witten, Karl Deisseroth, Yen-Yu Ian Shih, Garret D Stuber
Several neuropsychiatric conditions, such as addiction and schizophrenia, may arise in part from dysregulated activity of ventral tegmental area dopaminergic (TH(VTA)) neurons, as well as from more global maladaptation in neurocircuit function. However, whether TH(VTA) activity affects large-scale brain-wide function remains unknown. Here we selectively activated TH(VTA) neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging...
February 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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