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https://www.readbyqxmd.com/read/27896970/empowering-multi-cohort-gene-expression-analysis-to-increase-reproducibility
#1
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
#2
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
#3
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
#4
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
#5
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 7, 2016: Nature
https://www.readbyqxmd.com/read/27579481/molecular-and-cellular-mechanisms-for-trapping-and-activating-emotional-memories
#6
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
#7
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
#8
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...
August 24, 2016: Nature
https://www.readbyqxmd.com/read/27517089/lsps-optogenetics-to-improve-synaptic-connectivity-mapping-unmasking-the-role-of-basket-cell-mediated-feedforward-inhibition
#9
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
#10
Heather K Decot, Vijay Mk Namboodiri, Wei Gao, Jenna A McHenry, Joshua H Jennings, Sung-Ho Lee, Pranish A Kantak, Yu-ChiehJill Kao, Manasmita Das, Ilana B Witten, Karl Deisseroth, Yen-YuIan 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 (fMRI)...
August 12, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27511294/the-need-for-calcium-imaging-in-nonhuman-primates-new-motor-neuroscience-and-brain-machine-interfaces
#11
Daniel J O'Shea, Eric Trautmann, Chandramouli Chandrasekaran, Sergey Stavisky, Jonathan Kao, Maneesh Sahani, Stephen Ryu, Karl Deisseroth, Krishna V Shenoy
A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces...
August 7, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27484850/optogenetic-and-chemogenetic-strategies-for-sustained-inhibition-of-pain
#12
Shrivats M Iyer, Sam Vesuna, Charu Ramakrishnan, Karen Huynh, Stephanie Young, Andre Berndt, Soo Yeun Lee, Christopher J Gorini, Karl Deisseroth, Scott L Delp
Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination, and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27463673/competition-between-engrams-influences-fear-memory-formation-and-recall
#13
Asim J Rashid, Chen Yan, Valentina Mercaldo, Hwa-Lin Liz Hsiang, Sungmo Park, Christina J Cole, Antonietta De Cristofaro, Julia Yu, Charu Ramakrishnan, Soo Yeun Lee, Karl Deisseroth, Paul W Frankland, Sheena A Josselyn
Collections of cells called engrams are thought to represent memories. Although there has been progress in identifying and manipulating single engrams, little is known about how multiple engrams interact to influence memory. In lateral amygdala (LA), neurons with increased excitability during training outcompete their neighbors for allocation to an engram. We examined whether competition based on neuronal excitability also governs the interaction between engrams. Mice received two distinct fear conditioning events separated by different intervals...
July 22, 2016: Science
https://www.readbyqxmd.com/read/27387948/phototactic-guidance-of-a-tissue-engineered-soft-robotic-ray
#14
Sung-Jin Park, Mattia Gazzola, Kyung Soo Park, Shirley Park, Valentina Di Santo, Erin L Blevins, Johan U Lind, Patrick H Campbell, Stephanie Dauth, Andrew K Capulli, Francesco S Pasqualini, Seungkuk Ahn, Alexander Cho, Hongyan Yuan, Ben M Maoz, Ragu Vijaykumar, Jeong-Woo Choi, Karl Deisseroth, George V Lauder, L Mahadevan, Kevin Kit Parker
Inspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we created a biohybrid system that enables an artificial animal--a tissue-engineered ray--to swim and phototactically follow a light cue. By patterning dissociated rat cardiomyocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at 1/10 scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering, and turning maneuvers...
July 8, 2016: Science
https://www.readbyqxmd.com/read/27348215/segregated-cholinergic-transmission-modulates-dopamine-neurons-integrated-in-distinct-functional-circuits
#15
Daniel Dautan, Albert S Souza, Icnelia Huerta-Ocampo, Miguel Valencia, Maxime Assous, Ilana B Witten, Karl Deisseroth, James M Tepper, J Paul Bolam, Todor V Gerdjikov, Juan Mena-Segovia
Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA...
August 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27346529/dysregulation-of-prefrontal-cortex-mediated-slow-evolving-limbic-dynamics-drives-stress-induced-emotional-pathology
#16
Rainbo Hultman, Stephen D Mague, Qiang Li, Brittany M Katz, Nadine Michel, Lizhen Lin, Joyce Wang, Lisa K David, Cameron Blount, Rithi Chandy, David Carlson, Kyle Ulrich, Lawrence Carin, David Dunson, Sunil Kumar, Karl Deisseroth, Scott D Moore, Kafui Dzirasa
Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress...
July 20, 2016: Neuron
https://www.readbyqxmd.com/read/27334951/optogenetic-manipulation-of-neural-circuits-in-awake-marmosets
#17
Matthew MacDougall, Samuel U Nummela, Shanna Coop, Anita Disney, Jude F Mitchell, Cory T Miller
Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263-1268, 2005; Deisseroth K. Nat Methods 8: 26-29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates...
September 1, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27279213/midbrain-circuits-for-defensive-behaviour
#18
Philip Tovote, Maria Soledad Esposito, Paolo Botta, Fabrice Chaudun, Jonathan P Fadok, Milica Markovic, Steffen B E Wolff, Charu Ramakrishnan, Lief Fenno, Karl Deisseroth, Cyril Herry, Silvia Arber, Andreas Lüthi
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla...
June 1, 2016: Nature
https://www.readbyqxmd.com/read/27238866/endocannabinoid-modulation-of-orbitostriatal-circuits-gates-habit-formation
#19
Christina M Gremel, Jessica H Chancey, Brady K Atwood, Guoxiang Luo, Rachael Neve, Charu Ramakrishnan, Karl Deisseroth, David M Lovinger, Rui M Costa
Everyday function demands efficient and flexible decision-making that allows for habitual and goal-directed action control. An inability to shift has been implicated in disorders with impaired decision-making, including obsessive-compulsive disorder and addiction. Despite this, our understanding of the specific molecular mechanisms and circuitry involved in shifting action control remains limited. Here we identify an endogenous molecular mechanism in a specific cortical-striatal pathway that mediates the transition between goal-directed and habitual action strategies...
June 15, 2016: Neuron
https://www.readbyqxmd.com/read/27238022/wiring-and-molecular-features-of-prefrontal-ensembles-representing-distinct-experiences
#20
Li Ye, William E Allen, Kimberly R Thompson, Qiyuan Tian, Brian Hsueh, Charu Ramakrishnan, Ai-Chi Wang, Joshua H Jennings, Avishek Adhikari, Casey H Halpern, Ilana B Witten, Alison L Barth, Liqun Luo, Jennifer A McNab, Karl Deisseroth
A major challenge in understanding the cellular diversity of the brain has been linking activity during behavior with standard cellular typology. For example, it has not been possible to determine whether principal neurons in prefrontal cortex active during distinct experiences represent separable cell types, and it is not known whether these differentially active cells exert distinct causal influences on behavior. Here, we develop quantitative hydrogel-based technologies to connect activity in cells reporting on behavioral experience with measures for both brain-wide wiring and molecular phenotype...
June 16, 2016: Cell
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