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Chemogenetics

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https://www.readbyqxmd.com/read/29453443/role-of-the-mesolimbic-dopamine-system-in-relief-learning
#1
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29453206/elevation-of-hippocampal-neurogenesis-induces-a-temporally-graded-pattern-of-forgetting-of-contextual-fear-memories
#2
Aijing Gao, Frances Xia, Axel Guskjolen, Adam I Ramsaran, Adam Santoro, Sheena A Josselyn, Paul W Frankland
Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly-generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis...
February 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29445226/gcy-35-gcy-36-tax-2-tax-4-signalling-in-o-2-sensory-neurons-mediates-acute-functional-ethanol-tolerance-in-caenorhabditis-elegans
#3
Yuan-Hua Chen, Chang-Li Ge, Hong Wang, Ming-Hai Ge, Qing-Qin He, Yu Zhang, Wei Tian, Zheng-Xing Wu
Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29430793/medial-habenula-cholinergic-signaling-regulates-cocaine-associated-relapse-like-behavior
#4
Alberto J López, Yousheng Jia, André O White, Janine L Kwapis, Monica Espinoza, Philip Hwang, Rianne Campbell, Yasaman Alaghband, Om Chitnis, Dina P Matheos, Gary Lynch, Marcelo A Wood
Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse-like behaviors are known to be induced, in part, by re-exposure to drug-associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse have been identified and studied, a full description of the networks driving reinstatement of drug-seeking behaviors is lacking. One area that may provide further insight to the mechanisms of relapse is the habenula complex, an epithalamic region composed of lateral and medial (MHb) substructures, each with unique cell and target populations...
February 12, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29411708/-from-stone-craved-genes-to-michelangelo-significance-and-different-aspects-of-gene-environment-interaction
#5
Judit Lazary
Although genetic studies have improved a lot in recent years, without clinical relevance sometimes their significance is devalued. Reviewing the major milestones of psychogenomics it can be seen that break-through success is just a question of time. Investigations of direct effect of genetic variants on phenotypes have not yielded positive findings. However, an important step was taken by adapting the gene-environment interaction model. In this model genetic vulnerability stepped into the place of "stone craved" pathology...
December 2017: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/29410218/cholinergic-neurons-in-medial-septum-maintain-anxiety-like-behaviors-induced-by-chronic-inflammatory-pain
#6
Ying-Ying Jiang, Yu Zhang, Shuang Cui, Feng-Yu Liu, Ming Yi, You Wan
Cholinergic neurons in the medial septum (MS) participate in various cognitive and emotional behaviors, including innate anxiety. Chronic pain involves perceptual, cognitive and emotional components. Whether MS cholinergic system modulates pain-induced anxiety and the underlying neural circuits are involved remain unclear. In the present study, we showed that chemogenetic (DREADD) inhibition of MS cholinergic neurons relieved pain-induced anxiety-like behaviors in open field and elevated plus maze tests. Inhibiting the MS-rostral anterior cingulate cortex (rACC), but not the MS-ventral hippocampal CA1 pathway, achieved anxiolysis...
February 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29405119/thalamocortical-and-corticothalamic-pathways-differentially-contribute-to-goal-directed-behaviors-in-the-rat
#7
Fabien Alcaraz, Virginie Fresno, Alain R Marchand, Eric J Kremer, Etienne Coutureau, Mathieu Wolff
Highly distributed neural circuits are thought to support adaptive decision-making in volatile and complex environments. Notably, the functional interactions between prefrontal and reciprocally connected thalamic nuclei areas may be important when choices are guided by current goal value or action-outcome contingency. We examined the functional involvement of selected thalamocortical and corticothalamic pathways connecting the dorsomedial prefrontal cortex (dmPFC) and the mediodorsal thalamus (MD) in the behaving rat...
February 6, 2018: ELife
https://www.readbyqxmd.com/read/29359362/cholinergic-interneurons-in-the-rat-striatum-modulate-substitution-of-habits
#8
Sho Aoki, Andrew W Liu, Yumiko Akamine, Aya Zucca, Stefano Zucca, Jeffery R Wickens
Behavioral flexibility is crucial for adaptive behavior, and recent evidence suggests that cholinergic interneurons of the striatum play a distinct role. Previous studies of cholinergic function have focused on strategy switching by the dorsomedial or ventral striatum. We here investigated whether cholinergic interneurons in the dorsolateral striatum play a similar role at the level of switching of habitual responses. Because the dorsolateral striatum is particularly involved in habitual responding, we developed a habit substitution task that involved switching habitual lever-press responses to one side to another...
January 23, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29351511/chemogenetic-tools-for-causal-cellular-and-neuronal-biology
#9
Deniz Atasoy, Scott M Sternson
Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29338070/the-use-of-chemogenetics-in-behavioural-neuroscience-receptor-variants-targeting-approaches-and-caveats
#10
REVIEW
Erin J Campbell, Nathan J Marchant
The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29337301/hepatic-gi-signaling-regulates-whole-body-glucose-homeostasis
#11
Mario Rossi, Lu Zhu, Sara M McMillin, Sai Prasad Pydi, Shanu Jain, Lei Wang, Yinghong Cui, Regina J Lee, Amanda H Cohen, Hideaki Kaneto, Morris J Birnbaum, Yanling Ma, Yaron Rotman, Jie Liu, Travis J Cyphert, Toren Finkel, Owen P McGuinness, Jürgen Wess
An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29326268/mapping-the-malaria-parasite-druggable-genome-by-using-in-vitro-evolution-and-chemogenomics
#12
Annie N Cowell, Eva S Istvan, Amanda K Lukens, Maria G Gomez-Lorenzo, Manu Vanaerschot, Tomoyo Sakata-Kato, Erika L Flannery, Pamela Magistrado, Edward Owen, Matthew Abraham, Gregory LaMonte, Heather J Painter, Roy M Williams, Virginia Franco, Maria Linares, Ignacio Arriaga, Selina Bopp, Victoria C Corey, Nina F Gnädig, Olivia Coburn-Flynn, Christin Reimer, Purva Gupta, James M Murithi, Pedro A Moura, Olivia Fuchs, Erika Sasaki, Sang W Kim, Christine H Teng, Lawrence T Wang, Aslı Akidil, Sophie Adjalley, Paul A Willis, Dionicio Siegel, Olga Tanaseichuk, Yang Zhong, Yingyao Zhou, Manuel Llinás, Sabine Ottilie, Francisco-Javier Gamo, Marcus C S Lee, Daniel E Goldberg, David A Fidock, Dyann F Wirth, Elizabeth A Winzeler
Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29317484/chemogenetic-excitation-of-accumbens-projecting-infralimbic-cortical-neurons-blocks-toluene-induced-conditioned-place-preference
#13
Wesley N Wayman, John J Woodward
Abuse rates for inhalants among adolescents continue to be high, yet preclinical models for studying mechanisms underlying inhalant abuse remain limited. Our lab has previously shown that, in male rats, an acute binge-like exposure to toluene vapor that mimics human solvent abuse modifies the intrinsic excitability of medial prefrontal cortex (mPFC) pyramidal neurons projecting to the nucleus accumbens (NAc). These changes showed region (infralimbic; IL vs. prelimbic; PRL), layer (shallow; 2/3 vs. deep; 5/6), target (core vs...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29314464/chemogenetic-inhibition-of-direct-pathway-striatal-neurons-normalizes-pathological-cue-induced-reinstatement-of-drug-seeking-in-rats
#14
Lindsay M Yager, Aaron F Garcia, Elizabeth A Donckels, Susan M Ferguson
Addiction to drugs such as cocaine is marked by cycles of compulsive drug-taking and drug-seeking behavior. Although the transition to addiction is thought to recruit neural processes in dorsal striatum, little is known regarding the role of dorsal striatal projections to the substantia nigra (i.e. the direct pathway) in regulating these behaviors. Combining a Cre-recombinase-dependent chemogenetic approach with a cocaine self-administration paradigm that produces both low-risk and high-risk addiction phenotypes, we examined the effect of transiently decreasing direct pathway activity in the dorsomedial striatum on drug-taking and drug-seeking under conditions of normal and pathological drug use...
January 5, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29274662/inability-to-suppress-the-stress-induced-activation-of-the-hpa-axis-during-the-peripartum-period-engenders-deficits-in-postpartum-behaviors-in-mice
#15
Laverne Camille Melón, Andrew Hooper, Xuzhong Yang, Stephen J Moss, Jamie Maguire
The stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is normally suppressed during pregnancy. Dysregulation of the HPA axis has been proposed to play a role in postpartum depression. However, direct investigation into the relationship between the HPA axis and postpartum depression has been hindered by the lack of useful animal models. Building on our discovery of a role for the K+/Cl-co-transporter, KCC2, in the GABAergic regulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN), critical for mounting the body's physiological response to stress, we assessed the role of KCC2 in the regulation of the HPA axis during pregnancy and the postpartum period...
December 20, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29259187/the-interhemispheric-ca1-circuit-governs-rapid-generalisation-but-not-fear-memory
#16
Heng Zhou, Gui-Jing Xiong, Liang Jing, Ning-Ning Song, De-Lin Pu, Xun Tang, Xiao-Bing He, Fu-Qiang Xu, Jing-Fei Huang, Ling-Jiang Li, Gal Richter-Levin, Rong-Rong Mao, Qi-Xin Zhou, Yu-Qiang Ding, Lin Xu
Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29241540/lateral-hypothalamic-neurotensin-neurons-orchestrate-dual-weight-loss-behaviors-via-distinct-mechanisms
#17
Hillary L Woodworth, Bethany G Beekly, Hannah M Batchelor, Raluca Bugescu, Patricia Perez-Bonilla, Laura E Schroeder, Gina M Leinninger
The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated by distinct signaling pathways: Nts action via NtsR1 is essential for the anorectic effect of the LHA Nts circuit, but not for regulation of locomotor or drinking behavior...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29235461/oxytocin-enhances-observational-fear-in-mice
#18
Marc T Pisansky, Leah R Hanson, Irving I Gottesman, Jonathan C Gewirtz
Empathy is fundamental to human relations, but its neural substrates remain largely unknown. Here we characterize the involvement of oxytocin in the capacity of mice to display emotional state-matching, an empathy-like behavior. When exposed to a familiar conspecific demonstrator in distress, an observer mouse becomes fearful, as indicated by a tendency to freeze and subsequent efforts to escape. Both intranasal oxytocin administration and chemogenetic stimulation of oxytocin neurons render males sensitive to the distress of an unfamiliar mouse...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29191752/the-use-of-chemogenetic-approaches-to-study-the-physiological-roles-of-muscarinic-acetylcholine-receptors-in-the-central-nervous-system
#19
REVIEW
Sophie J Bradley, Andrew B Tobin, Rudi Prihandoko
Chemical genetic has played an important role in linking specific G protein-coupled receptor (GPCR) signalling to cellular processes involved in central nervous system (CNS) functions. Key to this approach has been the modification of receptor properties such that receptors no longer respond to endogenous ligands but rather can be activated selectively by synthetic ligands. Such modified receptors have been called Receptors Activated Solely by Synthetic Ligands (RASSLs) or Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
November 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29186699/seizure-induced-activation-of-the-hpa-axis-increases-seizure-frequency-and-comorbid-depression-like-behaviors
#20
Andrew Hooper, Rumzah Paracha, Jamie Maguire
Our laboratory recently demonstrated that seizures activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing circulating levels of corticosterone (O'Toole et al., 2013). Given the well-established proconvulsant actions of corticosterone, we hypothesized that seizure-induced activation of the HPA axis may contribute to future seizure susceptibility. Further, since hypercortisolism is associated with depression, we propose that seizure-induced activation of the HPA axis may contribute to comorbid depression and epilepsy...
November 26, 2017: Epilepsy & Behavior: E&B
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