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Chemogenetics

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https://www.readbyqxmd.com/read/27909152/involvement-of-mesolimbic-dopaminergic-network-in-neuropathic-pain-relief-by-treadmill-exercise-a-study-for-specific-neural-control-with-gi-dreadd-in-mice
#1
Kenta Wakaizumi, Takashige Kondo, Yusuke Hamada, Michiko Narita, Rui Kawabe, Hiroki Narita, Moe Watanabe, Shigeki Kato, Emiko Senba, Kazuto Kobayashi, Naoko Kuzumaki, Akihiro Yamanaka, Hiroshi Morisaki, Minoru Narita
BACKGROUND: Exercise alleviates pain and it is a central component of treatment strategy for chronic pain in clinical setting. However, little is known about mechanism of this exercise-induced hypoalgesia. The mesolimbic dopaminergic network plays a role in positive emotions to rewards including motivation and pleasure. Pain negatively modulates these emotions, but appropriate exercise is considered to activate the dopaminergic network. We investigated possible involvement of this network as a mechanism of exercise-induced hypoalgesia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27909104/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#2
J A Heinsbroek, D N Neuhofer, W C Griffin, G S Siegel, A-C Bobadilla, Y M Kupchik, P W Kalivas
Distinct populations of D1- and D2-dopamine receptor expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, while activity in D2-MSNs inhibits motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909096/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#3
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN), and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We previously demonstrated that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we use neuroanatomical tracing, immunofluorescence and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections co-express vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27893096/chemogenetic-activation-of-iprgcs-drives-changes-in-dark-adapted-scotopic-electroretinogram
#4
Nina Milosavljevic, Annette E Allen, Jasmina Cehajic-Kapetanovic, Robert J Lucas
Purpose: The purpose of this study was to investigate the impact of activating melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) on dark-adapted (scotopic) electroretinograms (ERG). Methods: We used mice (Opn4Cre/+) expressing cre recombinase in melanopsin-expressing cells for a targeted gene delivery of a chemogenetic Gq-coupled receptor, hM3Dq, to ipRGCs. Intraperitoneal injection of clozapine N-oxide (CNO) at 5 mg/kg was used for acute activation of hM3Dq and thus excitation of ipRGCs in darkness...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27890661/studying-brain-regulation-of-immunity-with-optogenetics-and-chemogenetics-a-new-experimental-platform
#5
REVIEW
Tamar Ben-Shaanan, Maya Schiller, Asya Rolls
The interactions between the brain and the immune system are bidirectional. Nevertheless, we have far greater understanding of how the immune system affects the brain than how the brain affects immunity. New technological developments such as optogenetics and chemogenetics (using DREADDs; Designer Receptors Exclusively Activated by Designer Drugs) can bridge this gap in our understanding, as they enable an unprecedented mechanistic and systemic analysis of the communication between the brain and the immune system...
November 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27882999/activation-of-ventral-tegmental-area-5-ht2c-receptors-reduces-incentive-motivation
#6
Lourdes Valencia-Torres, Cristian M Olarte-Sánchez, David J Lyons, Teodora Georgescu, Megan Greenwald-Yarnell, Martin G Myers, Christopher M Bradshaw, Lora K Heisler
Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice...
November 24, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27852779/ventral-pallidum-output-pathways-in-context-induced-reinstatement-of-alcohol-seeking
#7
Asheeta A Prasad, Gavan P McNally
: Ventral pallidum (VP) is a well-established locus for the reinforcing effects of drugs of abuse and reinstatement of drug seeking. However, VP neurons are at the origin of multiple output pathways, with strong projections to ventral tegmental area (VTA), subthalamic nucleus (STN), lateral hypothalamus, among others, and the roles of these VP output pathways in reinstatement of drug seeking remain poorly understood. Here we addressed these issues using a combination of neuroanatomical tracing and chemogenetic approaches...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27822508/clozapine-n-oxide-administration-produces-behavioral-effects-in-long-evans-rats-implications-for-designing-dreadd-experiments
#8
Duncan A A MacLaren, Richard W Browne, Jessica K Shaw, Sandhya Krishnan Radhakrishnan, Prachi Khare, Rodrigo A España, Stewart D Clark
Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des)...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27821603/preclinical-models-for-obesity-research
#9
REVIEW
Perry Barrett, Julian G Mercer, Peter J Morgan
A multi-dimensional strategy to tackle the global obesity epidemic requires an in-depth understanding of the mechanisms that underlie this complex condition. Much of the current mechanistic knowledge has arisen from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. These experimental models mimic certain aspects of the human condition and its root causes, particularly the over-consumption of calories and unbalanced diets. As with human obesity, obesity in rodents is the result of complex gene-environment interactions...
November 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27807162/an-inhibitory-septum-to-lateral-hypothalamus-circuit-that-suppresses-feeding
#10
Patrick Sweeney, Yunlei Yang
: Feeding behavior is orchestrated by neural circuits primarily residing in the hypothalamus and hindbrain. However, the relative influence of cognitive and emotional brain circuits to the feeding circuitry in the hypothalamus and hindbrain remains unclear. Here, using the cell-type selectivity of genetic methods, circuit mapping, and behavior assays, we sought to decipher neural circuits emanating from the septal nucleus to the lateral hypothalamus (LH) that contribute to neural regulation of food intake in mice...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27806306/in%C3%A2-vivo-interrogation-of-spinal-mechanosensory-circuits
#11
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/27799222/competitive-growth-enhances-conditional-growth-mutant-sensitivity-to-antibiotics-and-exposes-a-two-component-system-as-an-emerging-antibacterial-target-in-burkholderia-cenocepacia
#12
April S Gislason, Matthew Choy, Ruhi A M Bloodworth, Wubin Qu, Maria S Stietz, Xuan Li, Chenggang Zhang, Silvia T Cardona
Chemogenetic approaches to profile antibiotic mode of action are based on detecting differential sensitivity of engineered bacterial strains in which the antibacterial target (usually encoded by an essential gene) or an associated process are regulated. We previously developed an essential gene-knockdown mutant library in the multidrug resistant Burkholderia cenocepacia, by transposon-delivery of a rhamnose-inducible promoter. In this work, we used Illumina sequencing of multiplex-PCR amplified transposon junctions to track individual mutants during pooled growth in the presence of antibiotics...
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27790055/optogenetic-and-chemogenetic-approaches-for-studying-astrocytes-and-gliotransmitters
#13
REVIEW
Juwon Bang, Hak Yeong Kim, Hyosang Lee
The brain consists of heterogeneous populations of neuronal and non-neuronal cells. The revelation of their connections and interactions is fundamental to understanding normal brain functions as well as abnormal changes in pathological conditions. Optogenetics and chemogenetics have been developed to allow functional manipulations both in vitro and in vivo to examine causal relationships between cellular changes and functional outcomes. These techniques are based on genetically encoded effector molecules that respond exclusively to exogenous stimuli, such as a certain wavelength of light or a synthetic ligand...
October 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27789840/a-disynaptic-feedback-network-activated-by-experience-promotes-the-integration-of-new-granule-cells
#14
Diego D Alvarez, Damiana Giacomini, Sung Min Yang, Mariela F Trinchero, Silvio G Temprana, Karina A Büttner, Natalia Beltramone, Alejandro F Schinder
Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid-releasing interneurons (PV-INs) that feed back onto developing GCs...
October 28, 2016: Science
https://www.readbyqxmd.com/read/27767183/molecular-characterization-of-thy1-expressing-fear-inhibiting-neurons-within-the-basolateral-amygdala
#15
Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27748741/chemogenetic-activation-of-midbrain-dopamine-neurons-affects-attention-but-not-impulsivity-in-the-five-choice-serial-reaction-time-task-in-rats
#16
Linde Boekhoudt, Elisa S Voets, Jacques P Flores-Dourojeanni, Mieneke Cm Luijendijk, Louk Jmj Vanderschuren, Roger Ah Adan
Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats...
November 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27733612/sustained-gq-protein-signaling-disrupts-striatal-circuits-via-jnk
#17
Luigi Bellocchio, Andrea Ruiz-Calvo, Anna Chiarlone, Magali Cabanas, Eva Resel, Jean-René Cazalets, Cristina Blázquez, Yoon H Cho, Ismael Galve-Roperh, Manuel Guzmán
: The dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the Gs/Gi-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of Gq-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of Gq-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca(2+)/proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27721502/calcium-dysregulation-contributes-to-neurodegeneration-in-ftld-patient-ipsc-derived-neurons
#18
Keiko Imamura, Naruhiko Sahara, Nicholas M Kanaan, Kayoko Tsukita, Takayuki Kondo, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada, Koichi Kawakami, Akitsu Hotta, Satoshi Yawata, Dai Watanabe, Masato Hasegawa, John Q Trojanowski, Virginia M-Y Lee, Tetsuya Suhara, Makoto Higuchi, Haruhisa Inoue
Mutations in the gene MAPT encoding tau, a microtubules-associated protein, cause a subtype of familial neurodegenerative disorder, known as frontotemporal lobar degeneration tauopathy (FTLD-Tau), which presents with dementia and is characterized by atrophy in the frontal and temporal lobes of the brain. Although induced pluripotent stem cell (iPSC) technology has facilitated the investigation of phenotypes of FTLD-Tau patient neuronal cells in vitro, it remains unclear how FTLD-Tau patient neurons degenerate...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27712862/chemogenetic-activation-of-dopamine-neurons-in-the-ventral-tegmental-area-but-not-substantia-nigra-induces-hyperactivity-in-rats
#19
Linde Boekhoudt, Azar Omrani, Mieneke C M Luijendijk, Inge G Wolterink-Donselaar, Ellen C Wijbrans, Geoffrey van der Plasse, Roger A H Adan
Hyperactivity is a core symptom in various psychiatric disorders, including attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and anorexia nervosa. Although hyperactivity has been linked to dopaminergic signalling, the causal relationship between midbrain dopamine neuronal activity and locomotor hyperactivity remains unknown. In this study, we test whether increased dopamine neuronal activity is sufficient to induce locomotor hyperactivity. To do so, we used designer receptors exclusively activated by designer drugs (DREADD) to chemogenetically enhance neuronal activity in two main midbrain dopamine neuron populations, i...
October 3, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27707965/basal-ganglia-output-controls-active-avoidance-behavior
#20
Sebastian Hormigo, German Vega-Flores, Manuel A Castro-Alamancos
: Engrained avoidance behavior is highly adaptive when it keeps away harmful events and can be highly maladaptive when individuals elude harmless situations in anxiety disorders, but the neural circuits that mediate avoidance are poorly understood. Using DREADDs and optogenetics in mice, we show that the output of the basal ganglia through the substantia nigra pars reticulata (SNr) controls active avoidance. SNr excitation blocks avoidance to a conditioned sensory stimulus while preserving the ability to escape the harmful event...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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