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chemogenetics dreadds

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https://www.readbyqxmd.com/read/28193686/paraventricular-thalamus-balances-danger-and-reward
#1
Eun A Choi, Gavan P McNally
Foraging animals balance the need to seek food and energy against the accompanying dangers of injury and predation. To do so, they rely on learning systems encoding reward and danger. Whereas much is known about these separate learning systems, little is known about how they interact to shape and guide behavior. Here we show a key role for the rat paraventricular nucleus of the thalamus (PVT), a nucleus of the dorsal midline thalamus, in this interaction. First we show behavioral competition between reward and danger: the opportunity to seek food reward negatively modulates expression of species-typical defensive behavior...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28104285/resisting-the-urge-to-act-dreadds-modifying-habits
#2
Mark A G Eldridge, Barry J Richmond
Recently, Meyer and Bucci used chemogenetic technology - artificial excitatory and inhibitory receptors - to modulate neuronal activity in two connected brain regions in opposite directions simultaneously. This innovative manipulation revealed that the two regions studied, orbitofrontal cortex and nucleus accumbens, are not sequentially dependent during contextual decision-making.
February 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#3
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
#4
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/27956747/acute-engagement-of-gq-mediated-signaling-in-the-bed-nucleus-of-the-stria-terminalis-induces-anxiety-like-behavior
#5
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/27922009/pet-imaging-guided-chemogenetic-silencing-reveals-a-critical-role-of-primate-rostromedial-caudate-in-reward-evaluation
#6
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/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#7
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
#8
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/27909096/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#9
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/27890661/studying-brain-regulation-of-immunity-with-optogenetics-and-chemogenetics-a-new-experimental-platform
#10
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/27822508/clozapine-n-oxide-administration-produces-behavioral-effects-in-long-evans-rats-implications-for-designing-dreadd-experiments
#11
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/27767183/molecular-characterization-of-thy1-expressing-fear-inhibiting-neurons-within-the-basolateral-amygdala
#12
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/27733612/sustained-gq-protein-signaling-disrupts-striatal-circuits-via-jnk
#13
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/27712862/chemogenetic-activation-of-dopamine-neurons-in-the-ventral-tegmental-area-but-not-substantia-nigra-induces-hyperactivity-in-rats
#14
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...
November 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27707965/basal-ganglia-output-controls-active-avoidance-behavior
#15
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
https://www.readbyqxmd.com/read/27696530/stimulation-induced-transient-changes-in-neuronal-activity-blood-flow-and-n-acetylaspartate-content-in-rat-prefrontal-cortex-a-chemogenetic-fmrs-bold-study
#16
Morris H Baslow, Christopher K Cain, Robert Sears, Donald A Wilson, Alvin Bachman, Scott Gerum, David N Guilfoyle
Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA...
December 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27683912/chemogenetic-activation-of-an-extinction-neural-circuit-reduces-cue-induced-reinstatement-of-cocaine-seeking
#17
Isabel F Augur, Andrew R Wyckoff, Gary Aston-Jones, Peter W Kalivas, Jamie Peters
UNLABELLED: The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27605603/resolving-behavioral-output-via-chemogenetic-designer-receptors-exclusively-activated-by-designer-drugs
#18
C Joseph Burnett, Michael J Krashes
Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying behavioral outputs. They exhibit a number of advantages: they rely on cell-specific manipulations through canonical intracellular signaling pathways, they are easy and cost-effective to implement in a laboratory setting, and they are easily scalable for single-region or full-brain manipulations. On the other hand, DREADDs rely on ligand-G-protein-coupled receptor interactions, leading to coarse temporal dynamics...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27416078/dreadds-suppress-seizure-like-activity-in-a-mouse-model-of-pharmacoresistant-epileptic-brain-tissue
#19
N Avaliani, M Andersson, A H Runegaard, D Woldbye, M Kokaia
Epilepsy is a neurological disorder with a prevalence of ≈1% of general population. Available antiepileptic drugs (AEDs) have multiple side effects and are ineffective in 30% of patients. Therefore, development of effective treatment strategies is highly needed, requiring drug-screening models that are relevant and reliable. We investigated novel chemogenetic approach, using DREADDs (designer receptors exclusively activated by designer drugs) as possible inhibitor of epileptiform activity in organotypic hippocampal slice cultures (OHSCs)...
August 4, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27404844/chemogenetic-silencing-of-the-midline-and-intralaminar-thalamus-blocks-amygdala-kindled-seizures
#20
Evan Wicker, Patrick A Forcelli
Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures. Here, we examined a recently developed technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), as a means of chemogenetic silencing to attenuate limbic seizures...
September 2016: Experimental Neurology
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