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https://www.readbyqxmd.com/read/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#1
REVIEW
Grzegorz Dobrzanski, Małgorzata Kossut
The DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technique is a new chemogenetic approach allowing for selective and remote control of neural activity with a high degree of spatial resolution. Since its discovery in 2007 the DREADD technique was successfully employed into basic research, and together with the optogenetic method provided so far the best tool to influence the activity of the brain circuits and cell populations. The first aim of this review was to concisely describe the technique with regard to such issues like the history of its development, biochemistry as well as modes of the designer receptors delivery and expression...
October 29, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#2
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 demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#3
Michael C Chen, Ramalingam Vetrivelan, Chun-Ni Guo, Catie Chang, Patrick M Fuller, Jun Lu
Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep...
January 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28073937/activity-of-tachykinin1-expressing-pet1-raphe-neurons-modulates-the-drive-to-breathe
#4
Morgan L Hennessy, Andrea Corcoran, Rachael D Brust, Eugene E Nattie, Susan Dymecki
: Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the 5-HT system, which have borne out in functional studies, including the modulation of distinct facets of homeostatic control. These functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to co-express other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#5
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/28072397/agrp-neuron-activity-is-required-for-alcohol-induced-overeating
#6
Sarah Cains, Craig Blomeley, Mihaly Kollo, Romeo Rácz, Denis Burdakov
Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain's feeding circuits-the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger-display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28069760/axotomized-corticospinal-neurons-increase-supra-lesional-innervation-and-remain-crucial-for-skilled-reaching-after-bilateral-pyramidotomy
#7
Alice C Mosberger, Jenifer C Miehlbradt, Nadja Bjelopoljak, Marc P Schneider, Anna-Sophia Wahl, Benjamin V Ineichen, Miriam Gullo, Martin E Schwab
Skilled upper limb function heavily depends on the corticospinal tract. After bilateral lesions to this tract, motor control is disrupted but can be partially substituted by other motor systems to allow functional recovery. However, the remaining roles of motor cortex and especially of axotomized corticospinal neurons (CSNs) are not well understood. Using the single pellet retrieval task in adult rats, we induced significant recovery of skilled reaching after bilateral pyramidotomy by rehabilitative reaching training, and show that reach-related motor cortex activity, recorded in layer V, topographically reappeared shortly after axotomy...
January 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28039375/cholinergic-glutamatergic-and-gabaergic-neurons-of-the-ppt-have-distinct-effects-on-sleep-wake-behavior-in-mice
#8
Daniel Kroeger, Loris L Ferrari, Gaetan Petit, Carrie E Mahoney, Patrick M Fuller, Elda Arrigoni, Thomas E Scammell
: The pedunculopontine tegmental nucleus (PPT) has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic and GABAergic PPT cell groups in regulating cortical activity and behavioral state remains unknown...
December 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27980211/engineering-extrinsic-disorder-to-control-protein-activity-in-living-cells
#9
Onur Dagliyan, Miroslaw Tarnawski, Pei-Hsuan Chu, David Shirvanyants, Ilme Schlichting, Nikolay V Dokholyan, Klaus M Hahn
Optogenetic and chemogenetic control of proteins has revealed otherwise inaccessible facets of signaling dynamics. Here, we use light- or ligand-sensitive domains to modulate the structural disorder of diverse proteins, thereby generating robust allosteric switches. Sensory domains were inserted into nonconserved, surface-exposed loops that were tight and identified computationally as allosterically coupled to active sites. Allosteric switches introduced into motility signaling proteins (kinases, guanosine triphosphatases, and guanine exchange factors) controlled conversion between conformations closely resembling natural active and inactive states, as well as modulated the morphodynamics of living cells...
December 16, 2016: Science
https://www.readbyqxmd.com/read/27980115/role-of-dorsomedial-striatum-neuronal-ensembles-in-incubation-of-methamphetamine-craving-after-voluntary-abstinence
#10
Daniele Caprioli, Marco Venniro, Michelle Zhang, Jennifer M Bossert, Brandon L Warren, Bruce T Hope, Yavin Shaham
: We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral and dorsomedial striatum (DLS, DMS) in this incubation.We trained rats to self-administer palatable food pellets (6 days, 6-h/d) and methamphetamine (12 days, 6-h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/day) for 19 days...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27958714/a-chemogenetic-receptor-that-enhances-the-magnitude-and-frequency-of-glycinergic-inhibitory-postsynaptic-currents-without-inducing-a-tonic-chloride-flux
#11
Robiul Islam, Yan Zhang, Li Xu, Pankaj Sah, Joseph W Lynch
The gene transfer-mediated expression of inhibitory ion channels in nociceptive neurons holds promise for treating intractable pain. Chemogenetics, which involves expressing constructs activated by biologically inert molecules, is of particular interest as it permits tunable neuromodulation. However, current chloride-permeable chemogenetic constructs are problematic as they mediate a tonic chloride influx which over time would deplete the chloride electrochemical gradient and reduce inhibitory efficacy. Inflammatory pain sensitization can be caused by prostaglandin E2-mediated inhibition of glycinergic inhibitory postsynaptic currents in spinal nociceptive neurons...
December 15, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27956747/acute-engagement-of-gq-mediated-signaling-in-the-bed-nucleus-of-the-stria-terminalis-induces-anxiety-like-behavior
#12
C M Mazzone, D Pati, M Michaelides, J DiBerto, J H Fox, G Tipton, C Anderson, K Duffy, J M McKlveen, J A Hardaway, S T Magness, W A Falls, S E Hammack, Z A McElligott, Y L Hurd, T L Kash
The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27926856/insulin-dependent-activation-of-mch-neurons-impairs-locomotor-activity-and-insulin-sensitivity-in-obesity
#13
A Christine Hausen, Johan Ruud, Hong Jiang, Simon Hess, Hristo Varbanov, Peter Kloppenburg, Jens C Brüning
Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922009/pet-imaging-guided-chemogenetic-silencing-reveals-a-critical-role-of-primate-rostromedial-caudate-in-reward-evaluation
#14
Yuji Nagai, Erika Kikuchi, Walter Lerchner, Ken-Ichi Inoue, Bin Ji, Mark A G Eldridge, Hiroyuki Kaneko, Yasuyuki Kimura, Arata Oh-Nishi, Yukiko Hori, Yoko Kato, Toshiyuki Hirabayashi, Atsushi Fujimoto, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Masahiko Takada, Barry J Richmond, Takafumi Minamimoto
The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET)...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#15
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919319/chemogenetic-inhibition-of-the-medial-prefrontal-cortex-reverses-the-effects-of-rem-sleep-loss-on-sucrose-consumption
#16
Kristopher McEown, Yohko Takata, Yoan Cherasse, Nanae Nagata, Kosuke Aritake, Michael Lazarus
Rapid eye movement (REM) sleep loss is associated with increased consumption of weight-promoting foods. The prefrontal cortex (PFC) is thought to mediate reward anticipation. However, the precise role of the PFC in mediating reward responses to highly palatable foods (HPF) after REM sleep deprivation is unclear. We selectively reduced REM sleep in mice over a 25-48 hr period and chemogenetically inhibited the medial PFC (mPFC) by using an altered glutamate-gated and ivermectin-gated chloride channel that facilitated neuronal inhibition through hyperpolarizing infected neurons...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27918532/developmentally-defined-forebrain-circuits-regulate-appetitive-and-aversive-olfactory-learning
#17
Nagendran Muthusamy, Xuying Zhang, Caroline A Johnson, Prem N Yadav, H Troy Ghashghaei
Postnatal and adult neurogenesis are region- and modality-specific, but the significance of developmentally distinct neuronal populations remains unclear. We demonstrate that chemogenetic inactivation of a subset of forebrain and olfactory neurons generated at birth disrupts responses to an aversive odor. In contrast, novel appetitive odor learning is sensitive to inactivation of adult-born neurons, revealing that developmentally defined sets of neurons may differentially participate in hedonic aspects of sensory learning...
January 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/27918529/hsd2-neurons-in-the-hindbrain-drive-sodium-appetite
#18
Brooke C Jarvie, Richard D Palmiter
Sodium-depleted animals develop an appetite for aversive concentrations of sodium. Here we show that chemogenetic activation of aldosterone-sensitive neurons that express 11β-hydroxysteroid dehydrogenase type 2 (HSD2) in the nucleus of the solitary tract is sufficient to drive consumption of sodium-containing solutions in mice, independently of thirst or hunger. These HSD2-positive neurons are necessary for full expression of sodium appetite and have distinct downstream targets that are activated during sodium depletion...
December 5, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#19
Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong-Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J Richmond, Tetsuya Suhara, Makoto Higuchi
: Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [(11)C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI)...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#20
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
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