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Chemogenetics

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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
#1
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
#2
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
https://www.readbyqxmd.com/read/29184212/oxytocin-receptor-expressing-neurons-in-the-parabrachial-nucleus-regulate-fluid-intake
#3
Philip J Ryan, Silvano I Ross, Carlos A Campos, Victor A Derkach, Richard D Palmiter
Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection...
December 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29184200/altered-cerebellar-connectivity-in-autism-and-cerebellar-mediated-rescue-of-autism-related-behaviors-in-mice
#4
Catherine J Stoodley, Anila M D'Mello, Jacob Ellegood, Vikram Jakkamsetti, Pei Liu, Mary Beth Nebel, Jennifer M Gibson, Elyza Kelly, Fantao Meng, Christopher A Cano, Juan M Pascual, Stewart H Mostofsky, Jason P Lerch, Peter T Tsai
Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model...
December 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29184183/optogenetic-and-chemogenetic-techniques-for-neurogastroenterology
#5
REVIEW
Werend Boesmans, Marlene M Hao, Pieter Vanden Berghe
Optogenetics and chemogenetics comprise a wide variety of applications in which genetically encoded actuators and indicators are used to modulate and monitor activity with high cellular specificity. Over the past 10 years, development of these genetically encoded tools has contributed tremendously to our understanding of integrated physiology. In concert with the continued refinement of probes, strategies to target transgene expression to specific cell types have also made much progress in the past 20 years...
November 29, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29183687/functional-role-for-cortical-striatal-circuitry-in-modulating-alcohol-self-administration
#6
Anel A Jaramillo, Patrick A Randall, Spencer Stewart, Brayden Fortino, Kalynn VanVoorhies, Joyce Besheer
The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions...
November 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29170645/drugs-interfering-with-muscarinic-acetylcholine-receptors-and-their-effects-on-place-navigation
#7
REVIEW
Jan Svoboda, Anna Popelikova, Ales Stuchlik
Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks. However, many of these results may be potentially confounded by disruptions of functions other than spatial learning and memory...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29153928/enhancing-excitability-of-dopamine-neurons-promotes-motivational-behaviour-through-increased-action-initiation
#8
Linde Boekhoudt, Ellen C Wijbrans, Jodie H K Man, Mieneke C M Luijendijk, Johannes W de Jong, Geoffrey van der Plasse, Louk J M J Vanderschuren, Roger A H Adan
Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted...
November 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29134962/role-of-glutamatergic-projections-from-the-ventral-ca1-to-infralimbic-cortex-in-context-induced-reinstatement-of-heroin-seeking
#9
Na Wang, Feifei Ge, Cailian Cui, Yijing Li, Xiaowei Sun, Linlin Sun, Xinjuan Wang, Shuli Liu, Haolin Zhang, Yan Liu, Meng Jia, Mingda Yang
The prelimbic cortex (PL) and infralimbic cortex (IL) play a role in context-induced reinstatement of heroin seeking in an animal model of drug relapse. Both the PL and IL receive direct glutamatergic projections from the ventral CA1 (vCA1), which is also involved in context-induced reinstatement of cocaine and heroin seeking. Here we studied the role of vCA1-PL and vCA1-IL projections in context-induced reinstatement of heroin seeking by using electrophysiological, neuropharmacological, chemogenetic and molecular methods...
November 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29123082/supramammillary-glutamate-neurons-are-a-key-node-of-the-arousal-system
#10
Nigel P Pedersen, Loris Ferrari, Anne Venner, Joshua L Wang, Stephen B G Abbott, Nina Vujovic, Elda Arrigoni, Clifford B Saper, Patrick M Fuller
Basic and clinical observations suggest that the caudal hypothalamus comprises a key node of the ascending arousal system, but the cell types underlying this are not fully understood. Here we report that glutamate-releasing neurons of the supramammillary region (SuM(vglut2)) produce sustained behavioral and EEG arousal when chemogenetically activated. This effect is nearly abolished following selective genetic disruption of glutamate release from SuM(vglut2) neurons. Inhibition of SuM(vglut2) neurons decreases and fragments wake, also suppressing theta and gamma frequency EEG activity...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29121220/pathway-specific-control-of-striatal-neuron-vulnerability-by-corticostriatal-cannabinoid-cb1-receptors
#11
Andrea Ruiz-Calvo, Irene B Maroto, Raquel Bajo-Grañeras, Anna Chiarlone, Ángel Gaudioso, José J Ferrero, Eva Resel, José Sánchez-Prieto, José A Rodríguez-Navarro, Giovanni Marsicano, Ismael Galve-Roperh, Luigi Bellocchio, Manuel Guzmán
The vast majority of neurons within the striatum are GABAergic medium spiny neurons (MSNs), which receive glutamatergic input from the cortex and thalamus, and form two major efferent pathways: the direct pathway, expressing dopamine D1 receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified in animal models of striatal damage, the molecular factors that dictate a selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown...
October 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29118216/circuit-and-synaptic-plasticity-mechanisms-of-drug-relapse
#12
Yan Dong, Jane R Taylor, Marina E Wolf, Yavin Shaham
High rates of relapse to drug use during abstinence is a defining feature of human drug addiction. This clinical scenario has been studied at the preclinical level using different animal models in which relapse to drug seeking is assessed after cessation of operant drug self-administration in rodents and monkeys. In our Society for Neuroscience (SFN) session entitled "Circuit and Synaptic Plasticity Mechanisms of Drug Relapse," we will discuss new developments of our understanding of circuits and synaptic plasticity mechanisms of drug relapse from studies combining established and novel animal models with state-of-the-art cellular, electrophysiology, anatomical, chemogenetic, and optogenetic methods...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29118105/neuropeptide-s-activates-paraventricular-oxytocin-neurons-to-induce-anxiolysis
#13
Thomas Grund, Stephanie Goyon, Yuting Li, Marina Eliava, Haikun Liu, Alexandre Charlet, Valery Grinevich, Inga D Neumann
Neuropeptides, such as neuropeptide S (NPS) and oxytocin (OXT) represent potential options for the treatment of anxiety disorders due to their potent anxiolytic profile. In this study, we aimed to reveal the mechanisms underlying the behavioral action of NPS, and present a chain of evidence that the effects of NPS within the hypothalamic paraventricular nucleus (PVN) are mediated via actions on local OXT neurons in male Wistar rats. First, retrograde studies identified NPS fibers originating in the brainstem locus coeruleus and projecting to the PVN...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29114861/kappa-opioid-receptors-regulate-hippocampal-synaptic-homeostasis-and-epileptogenesis
#14
Bridget N Queenan, Raymond L Dunn, Victor R Santos, Yang Feng, Megan N Huizenga, Robert J Hammack, Stefano Vicini, Patrick A Forcelli, Daniel T S Pak
OBJECTIVE: Homeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo. METHODS: We previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functional changes...
November 8, 2017: Epilepsia
https://www.readbyqxmd.com/read/29106710/investigating-metabolic-regulation-using-targeted-neuromodulation
#15
REVIEW
Kavya Devarakonda, Sarah Stanley
The central nervous system (CNS) plays a vital role in regulating energy balance and metabolism. Over the last 50 years, studies in animal models have allowed us to identify critical CNS regions involved in these processes and even crucial cell populations. Now, techniques for genetically and anatomically targeted manipulation of specific neural populations using light (optogenetic), ligands (chemogenetic), or magnetic fields (radiogenetic/magnetogenetic) allow detailed investigation of circuits involved in metabolic regulation...
November 6, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29106571/retrieval-induced-upregulation-of-tet3-in-pyramidal-neurons-of-the-dorsal-hippocampus-mediates-cocaine-associated-memory-reconsolidation
#16
Cao Liu, Xue Sun, Zhilin Wang, Qiumin Le, Peipei Liu, Changyou Jiang, Feifei Wang, Lan Ma
Background: Memory retrieval refers to re-exposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods: We used cocaine-induced conditioned place preference (CPP) to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dHC...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29103805/a-genetically-defined-circuit-for-arousal-from-sleep-during-hypercapnia
#17
Satvinder Kaur, Joshua L Wang, Loris Ferrari, Stephen Thankachan, Daniel Kroeger, Anne Venner, Michael Lazarus, Andrew Wellman, Elda Arrigoni, Patrick M Fuller, Clifford B Saper
The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRP neurons caused wakefulness, whereas optogenetic inhibition of PBelCGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29079819/perturbed-wnt-signaling-leads-to-neuronal-migration-delay-altered-interhemispheric-connections-and-impaired-social-behavior
#18
Riccardo Bocchi, Kristof Egervari, Laura Carol-Perdiguer, Beatrice Viale, Charles Quairiaux, Mathias De Roo, Michael Boitard, Suzanne Oskouie, Patrick Salmon, Jozsef Z Kiss
Perturbed neuronal migration and circuit development have been implicated in the pathogenesis of neurodevelopmental diseases; however, the direct steps linking these developmental errors to behavior alterations remain unknown. Here we demonstrate that Wnt/C-Kit signaling is a key regulator of glia-guided radial migration in rat somatosensory cortex. Transient downregulation of Wnt signaling in migrating, callosal projection neurons results in delayed positioning in layer 2/3. Delayed neurons display reduced neuronal activity with impaired afferent connectivity causing permanent deficit in callosal projections...
October 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29074844/limiting-habenular-hyperactivity-ameliorates-maternal-separation-driven-depressive-like-symptoms
#19
Anna Tchenio, Salvatore Lecca, Kristina Valentinova, Manuel Mameli
Early-life stress, including maternal separation (MS), increases the vulnerability to develop mood disorders later in life, but the underlying mechanisms remain elusive. We report that MS promotes depressive-like symptoms in mice at a mature stage of life. Along with this behavioral phenotype, MS drives reduction of GABAB-GIRK signaling and the subsequent lateral habenula (LHb) hyperexcitability-an anatomical substrate devoted to aversive encoding. Attenuating LHb hyperactivity using chemogenetic tools and deep-brain stimulation ameliorates MS depressive-like symptoms...
October 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/29069598/brain-wide-mapping-of-endogenous-serotonergic-transmission-via-chemogenetic-fmri
#20
Andrea Giorgi, Sara Migliarini, Alberto Galbusera, Giacomo Maddaloni, Maddalena Mereu, Giulia Margiani, Marta Gritti, Silvia Landi, Francesco Trovato, Sine Mandrup Bertozzi, Andrea Armirotti, Gian Michele Ratto, Maria Antonietta De Luca, Raffaella Tonini, Alessandro Gozzi, Massimo Pasqualetti
Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, it remains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by designed drugs (DREADD)-based chemogenetics and functional magnetic resonance imaging (fMRI), an approach we term "chemo-fMRI," to causally probe the brain-wide substrates modulated by endogenous serotonergic activity...
October 24, 2017: Cell Reports
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