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Designer Receptor Exclusively Activated by a Designer Drug (DREADD)

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https://www.readbyqxmd.com/read/28830762/contribution-of-amygdala-crf-neurons-to-chronic-pain
#1
Matthew Andreoli, Tanvi Marketkar, Eugene Dimitrov
We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord...
August 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28794102/optogenetics-and-pharmacogenetics-principles-and-applications
#2
Jingwei Jiang, Huxing Cui, Kamal Rahmouni
Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin and archaerhodopsins) from the bacteria has made it possible to utilize light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G-protein coupled receptors which can be activated by otherwise inert drug-like small molecules such as the Designer Receptors Exclusively Activated by Designer Drug (DREADD) - a form of chemogenetics...
August 9, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28774929/chemogenetics-revealed-dreadd-occupancy-and-activation-via-converted-clozapine
#3
Juan L Gomez, Jordi Bonaventura, Wojciech Lesniak, William B Mathews, Polina Sysa-Shah, Lionel A Rodriguez, Randall J Ellis, Christopher T Richie, Brandon K Harvey, Robert F Dannals, Martin G Pomper, Antonello Bonci, Michael Michaelides
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency...
August 4, 2017: Science
https://www.readbyqxmd.com/read/28752052/the-role-of-ghrelin-responsive-mediobasal-hypothalamic-neurons-in-mediating-feeding-responses-to-fasting
#4
Bharath K Mani, Sherri Osborne-Lawrence, Mathieu Mequinion, Sydney Lawrence, Laurent Gautron, Zane B Andrews, Jeffrey M Zigman
OBJECTIVE: Ghrelin is a stomach-derived hormone that affects food intake and regulates blood glucose. The best-characterized actions of ghrelin are mediated by its binding to and activation of the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Adequate examination of the identity, function, and relevance of specific subsets of GHSR-expressing neurons has been hampered by the absence of a suitable Cre recombinase (Cre)-expressing mouse line with which to manipulate gene expression in a targeted fashion within GHSR-expressing neurons...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28680103/chemogenetic-silencing-of-gabaergic-dorsal-horn-interneurons-induces-morphine-resistant-spontaneous-nocifensive-behaviours
#5
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677202/dreadd-induced-silencing-of-the-medial-amygdala-reduces-the-preference-for-male-pheromones-and-the-expression-of-lordosis-in-estrous-female-mice
#6
Elizabeth A McCarthy, Arman Maqsudlu, Matthew Bass, Sofia Georghiou, James A Cherry, Michael J Baum
Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28673934/activation-of-sf1-neurons-in-the-ventromedial-hypothalamus-by-dreadd-technology-increases-insulin-sensitivity-in-peripheral-tissues
#7
Eulalia A Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen-Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi
The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, whereas this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology...
July 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28664926/memory-retention-involves-the-ventrolateral-orbitofrontal-cortex-comparison-with-the-basolateral-amygdala
#8
K S Zimmermann, C Li, D G Rainnie, K J Ressler, S L Gourley
The orbitofrontal cortex (OFC) is thought to link stimuli and actions with anticipated outcomes in order to sustain flexible behavior in an ever-changing environment. How it retains these associations to guide future behavior is less well-defined. Here we focused on one subregion of this heterogeneous structure, the ventrolateral OFC (VLO). CaMKII-driven inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were infused and subsequently activated by their ligand Clozapine-N-oxide (CNO) in conjunction with fear extinction training (a form of aversive conditioning) and response-outcome conditioning (a form of appetitive conditioning)...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28664636/chemogenetic-inhibition-reveals-midline-thalamic-nuclei-and-thalamo-accumbens-projections-mediate-cocaine-seeking-in-rats
#9
Amanda M Wunsch, Lindsay M Yager, Elizabeth A Donckels, Calvin T Le, John F Neumaier, Susan M Ferguson
Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of how this circuit regulates drug-seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical-basal ganglia-thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28623920/ketamine-induced-apoptosis-in-the-mouse-cerebral-cortex-follows-similar-characteristic-of-physiological-apoptosis-and-can-be-regulated-by-neuronal-activity
#10
Qi Wang, Feng-Yan Shen, Rong Zou, Jing-Jing Zheng, Xiang Yu, Ying-Wei Wang
The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry...
June 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28609587/chemogenetic-modulation-of-g-protein-coupled-receptor-signalling-in-visual-attention-research
#11
REVIEW
Søren H Jørgensen, Ciarán Martin Fitzpatrick, Ulrik Gether, David P D Woldbye, Andreas T Sørensen
Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attentional control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been a major area of investigation, it has proven difficult to accurately associate specific neuronal projections, cell types, neurotransmitter systems and receptors with distinct phenotypes owing to its complexity. In this MiniReview, we present a recently invented technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
June 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28502844/a-novel-approach-to-map-induced-activation-of-neuronal-networks-using-chemogenetics-and-functional-neuroimaging-in-rats-a-proof-of-concept-study-on-the-mesocorticolimbic-system
#12
Theresia J M Roelofs, Jeroen P H Verharen, Geralda A F van Tilborg, Linde Boekhoudt, Annette van der Toorn, Johannes W de Jong, Mieneke C M Luijendijk, Willem M Otte, Roger A H Adan, Rick M Dijkhuizen
Linking neural circuit activation at whole-brain level to neuronal activity at cellular level remains one of the major challenges in neuroscience research. We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic or mesocortical pathways, i...
May 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28498919/chemicogenetic-restoration-of-the-prefrontal-cortex-to-amygdala-pathway-ameliorates-stress-induced-deficits
#13
Jing Wei, Ping Zhong, Luye Qin, Tao Tan, Zhen Yan
Corticosteroid stress hormones exert a profound impact on cognitive and emotional processes. Understanding the neuronal circuits that are altered by chronic stress is important for counteracting the detrimental effects of stress in a brain region- and cell type-specific manner. Using the chemogenetic tool, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the remote, noninvasive and long-lasting modulation of cellular activity and signal transduction in discrete neuronal populations in vivo, we sought to identify the specific pathways that play an essential role in stress responses...
May 11, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-potassium-channel
#14
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome. Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
August 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28489327/new-directions-for-the-treatment-of-depression-targeting-the-photic-regulation-of-arousal-and-mood-pram-pathway
#15
REVIEW
Hannah E Bowrey, Morgan H James, Gary Aston-Jones
Both preclinical and clinical studies demonstrate that depression is strongly associated with reduced light availability, which in turn contributes to decreased function of brain regions that control mood. Here, we review findings that support a critical pathway for the control of mood that depends upon ambient light. We put forward a novel hypothesis, functionally linking retina to locus coeruleus (LC) in depression, and discuss the role of norepinephrine in affective disease. Finally, we discuss how utilizing the chemogenetic tool Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to precisely control this retina-LC circuit may be used as a novel therapeutic to treat depression...
July 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/28461695/a-hippocampus-to-prefrontal-cortex-neural-pathway-inhibits-food-motivation-through-glucagon-like-peptide-1-signaling
#16
T M Hsu, E E Noble, C M Liu, A M Cortella, V R Konanur, A N Suarez, D J Reiner, J D Hahn, M R Hayes, S E Kanoski
The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28451710/thalamic-inputs-to-dorsomedial-striatum-are-involved-in-inhibitory-control-evidence-from-the-five-choice-serial-reaction-time-task-in-rats
#17
Jasjot Saund, Daniel Dautan, Claire Rostron, Gonzalo P Urcelay, Todor V Gerdjikov
RATIONALE: Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. OBJECTIVES: Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats...
August 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#18
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414301/striatopallidal-dysfunction-underlies-repetitive-behavior-in-shank3-deficient-model-of-autism
#19
Wenting Wang, Chenchen Li, Qian Chen, Marie-Sophie van der Goes, James Hawrot, Annie Y Yao, Xian Gao, Congyi Lu, Ying Zang, Qiangge Zhang, Katherine Lyman, Dongqing Wang, Baolin Guo, Shengxi Wu, Charles R Gerfen, Zhanyan Fu, Guoping Feng
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28386207/activation-of-the-ventral-tegmental-area-increased-wakefulness-in-mice
#20
Huan-Xin Sun, Dian-Ru Wang, Chen-Bo Ye, Zhen-Zhen Hu, Chen-Yao Wang, Zhi-Li Huang, Su-Rong Yang
The ventral tegmental area (VTA) is crucial for brain functions, such as voluntary movement and cognition; however, the role of VTA in sleep-wake regulation when directly activated or inhibited remains unknown. In this study, we investigated the effects of activation or inhibition of VTA neurons on sleep-wake behavior using the pharmacogenetic "designer receptors exclusively activated by designer drugs (DREADD)" approach. Immunohistochemistry staining was performed to confirm the microinjection sites, and combined with electrophysiological experiments, to determine whether the VTA neurons were activated or inhibited...
2017: Sleep and Biological Rhythms
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