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https://www.readbyqxmd.com/read/28902833/rabies-screen-reveals-gpe-control-of-cocaine-triggered-plasticity
#1
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 21, 2017: Nature
https://www.readbyqxmd.com/read/28893946/a-radial-axis-defined-by-semaphorin-to-neuropilin-signaling-controls-pancreatic-islet-morphogenesis
#2
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...
October 15, 2017: Development
https://www.readbyqxmd.com/read/28768803/modulation-of-prefrontal-cortex-excitation-inhibition-balance-rescues-social-behavior-in-cntnap2-deficient-mice
#3
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/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
#4
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/28303019/integration-of-optogenetics-with-complementary-methodologies-in-systems-neuroscience
#5
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/27991900/molecular-interrogation-of-hypothalamic-organization-reveals-distinct-dopamine-neuronal-subtypes
#6
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/27556938/serotonin-engages-an-anxiety-and-fear-promoting-circuit-in-the-extended-amygdala
#7
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/27515791/coordination-of-brain-wide-activity-dynamics-by-dopaminergic-neurons
#8
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
https://www.readbyqxmd.com/read/27387948/phototactic-guidance-of-a-tissue-engineered-soft-robotic-ray
#9
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/27346529/dysregulation-of-prefrontal-cortex-mediated-slow-evolving-limbic-dynamics-drives-stress-induced-emotional-pathology
#10
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/27238866/endocannabinoid-modulation-of-orbitostriatal-circuits-gates-habit-formation
#11
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/26878381/simultaneous-fast-measurement-of-circuit-dynamics-at-multiple-sites-across-the-mammalian-brain
#12
Christina K Kim, Samuel J Yang, Nandini Pichamoorthy, Noah P Young, Isaac Kauvar, Joshua H Jennings, Talia N Lerner, Andre Berndt, Soo Yeun Lee, Charu Ramakrishnan, Thomas J Davidson, Masatoshi Inoue, Haruhiko Bito, Karl Deisseroth
Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior...
April 2016: Nature Methods
https://www.readbyqxmd.com/read/26699047/extended-field-of-view-and-increased-signal-3d-holographic-illumination-with-time-division-multiplexing
#13
REVIEW
Samuel J Yang, William E Allen, Isaac Kauvar, Aaron S Andalman, Noah P Young, Christina K Kim, James H Marshel, Gordon Wetzstein, Karl Deisseroth
Phase spatial light modulators (SLMs) are widely used for generating multifocal three-dimensional (3D) illumination patterns, but these are limited to a field of view constrained by the pixel count or size of the SLM. Further, with two-photon SLM-based excitation, increasing the number of focal spots penalizes the total signal linearly--requiring more laser power than is available or can be tolerated by the sample. Here we analyze and demonstrate a method of using galvanometer mirrors to time-sequentially reposition multiple 3D holograms, both extending the field of view and increasing the total time-averaged two-photon signal...
December 14, 2015: Optics Express
https://www.readbyqxmd.com/read/26472906/a-skin-inspired-organic-digital-mechanoreceptor
#14
Benjamin C-K Tee, Alex Chortos, Andre Berndt, Amanda Kim Nguyen, Ariane Tom, Allister McGuire, Ziliang Carter Lin, Kevin Tien, Won-Gyu Bae, Huiliang Wang, Ping Mei, Ho-Hsiu Chou, Bianxiao Cui, Karl Deisseroth, Tse Nga Ng, Zhenan Bao
Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels...
October 16, 2015: Science
https://www.readbyqxmd.com/read/26436451/projections-from-neocortex-mediate-top-down-control-of-memory-retrieval
#15
Priyamvada Rajasethupathy, Sethuraman Sankaran, James H Marshel, Christina K Kim, Emily Ferenczi, Soo Yeun Lee, Andre Berndt, Charu Ramakrishnan, Anna Jaffe, Maisie Lo, Conor Liston, Karl Deisseroth
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...
October 29, 2015: Nature
https://www.readbyqxmd.com/read/26374073/fda-approval-blinatumomab
#16
Donna Przepiorka, Chia-Wen Ko, Albert Deisseroth, Carolyn L Yancey, Reyes Candau-Chacon, Haw-Jyh Chiu, Brenda J Gehrke, Candace Gomez-Broughton, Robert C Kane, Susan Kirshner, Nitin Mehrotra, Tiffany K Ricks, Deborah Schmiel, Pengfei Song, Ping Zhao, Qing Zhou, Ann T Farrell, Richard Pazdur
On December 3, 2014, the FDA granted accelerated approval of blinatumomab (Blincyto; Amgen, Inc.) for treatment of Philadelphia chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL). Blinatumomab is a recombinant murine protein that acts as a bispecific CD19-directed CD3 T-cell engager. The basis for the approval was a single-arm trial with 185 evaluable adults with R/R ALL. The complete remission (CR) rate was 32% [95% confidence interval (CI), 26%-40%], and the median duration of response was 6...
September 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26232229/intact-brain-analyses-reveal-distinct-information-carried-by-snc-dopamine-subcircuits
#17
Talia N Lerner, Carrie Shilyansky, Thomas J Davidson, Kathryn E Evans, Kevin T Beier, Kelly A Zalocusky, Ailey K Crow, Robert C Malenka, Liqun Luo, Raju Tomer, Karl Deisseroth
Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc)...
July 30, 2015: Cell
https://www.readbyqxmd.com/read/26030846/excitatory-transmission-at-thalamo-striatal-synapses-mediates-susceptibility-to-social-stress
#18
Daniel J Christoffel, Sam A Golden, Jessica J Walsh, Kevin G Guise, Mitra Heshmati, Allyson K Friedman, Aditi Dey, Milo Smith, Nicole Rebusi, Madeline Pfau, Jessica L Ables, Hossein Aleyasin, Lena A Khibnik, Georgia E Hodes, Gabriel A Ben-Dor, Karl Deisseroth, Matthew L Shapiro, Robert C Malenka, Ines Ibanez-Tallon, Ming-Hu Han, Scott J Russo
Postsynaptic remodeling of glutamatergic synapses on ventral striatum (vSTR) medium spiny neurons (MSNs) is critical for shaping stress responses. However, it is unclear which presynaptic inputs are involved. Susceptible mice exhibited increased synaptic strength at intralaminar thalamus (ILT), but not prefrontal cortex (PFC), inputs to vSTR MSNs following chronic social stress. Modulation of ILT-vSTR versus PFC-vSTR neuronal activity differentially regulated dendritic spine plasticity and social avoidance.
July 2015: Nature Neuroscience
https://www.readbyqxmd.com/read/25995461/the-contribution-of-raised-intraneuronal-chloride-to-epileptic-network-activity
#19
Hannah Alfonsa, Edward M Merricks, Neela K Codadu, Mark O Cunningham, Karl Deisseroth, Claudia Racca, Andrew J Trevelyan
Altered inhibitory function is an important facet of epileptic pathology. A key concept is that GABAergic activity can become excitatory if intraneuronal chloride rises. However, it has proved difficult to separate the role of raised chloride from other contributory factors in complex network phenomena, such as epileptic pathology. Therefore, we asked what patterns of activity are associated with chloride dysregulation by making novel use of Halorhodopsin to load clusters of mouse pyramidal cells artificially with Cl(-)...
May 20, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25687774/daytime-spikes-in-dopaminergic-activity-drive-rapid-mood-cycling-in-mice
#20
M M Sidor, S M Spencer, K Dzirasa, P K Parekh, K M Tye, M R Warden, R N Arey, J F Enwright, J P R Jacobsen, S Kumar, E M Remillard, M G Caron, K Deisseroth, C A McClung
No abstract text is available yet for this article.
November 2015: Molecular Psychiatry
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