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https://www.readbyqxmd.com/read/29338070/the-use-of-chemogenetics-in-behavioural-neuroscience-receptor-variants-targeting-approaches-and-caveats
#1
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/29336819/identification-of-a-corticohabenular-circuit-regulating-socially-directed-behavior
#2
Madhurima Benekareddy, Tevye Jason Stachniak, Andreas Bruns, Frederic Knoflach, Markus von Kienlin, Basil Künnecke, Anirvan Ghosh
BACKGROUND: The prefrontal cortex (PFC) has been implicated in the pathophysiology of social dysfunction, but the specific circuit partners mediating PFC function in health and disease are unclear. METHODS: The excitatory designer receptor exclusively activated by designer drugs (DREADD) hM3Dq was used to induce PFC activation during social behavior measured in the three-chamber sociability assay (rats/mice). Functional magnetic resonance imaging was combined with hM3Dq-mediated PFC activation to identify novel nodes in the "social brain" in a hypothesis-free manner...
December 2, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29335360/activity-in-the-ventral-medial-prefrontal-cortex-is-necessary-for-the-therapeutic-effects-of-extinction-in-rats
#3
Elizabeth A Fucich, Denisse Paredes, Madeleine O Saunders, David A Morilak
Poor response and high relapse rates remain problematic in the treatment of stress-related psychiatric disorders like depression and posttraumatic stress disorder (PTSD). While mechanisms of pharmacotherapies are intensely studied, little is known about mechanisms of behavioral therapy that could inform improved treatments. We have previously demonstrated the therapeutic effects of extinction learning as a behavioral intervention modeling exposure therapy in rats. In the present study, we tested the hypothesis that activity in the ventral medial prefrontal cortex (vmPFC) during extinction is necessary for its therapeutic effects...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29333487/activation-of-the-medial-prefrontal-cortex-reverses-cognitive-and-respiratory-symptoms-in-a-mouse-model-of-rett-syndrome
#4
C James Howell, Michael P Sceniak, Min Lang, Wenceslas Krakowiecki, Fatimah E Abouelsoud, Saloni U Lad, Heping Yu, David M Katz
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions that are abnormal in RTT patients, ranging from learning and memory to regulation of visceral homeostasis (Riga et al...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29317484/chemogenetic-excitation-of-accumbens-projecting-infralimbic-cortical-neurons-blocks-toluene-induced-conditioned-place-preference
#5
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/29303143/cno-evil-considerations-for-the-use-of-dreadds-in-behavioral-neuroscience
#6
Stephen V Mahler, Gary Aston-Jones
Neuropsychopharmacology accepted article preview online, 05 January 2018. doi:10.1038/npp.2017.299.
January 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29222692/advances-in-understanding-hilar-mossy-cells-of-the-dentate-gyrus
#7
REVIEW
Helen E Scharfman
Hilar mossy cells (MCs) of the dentate gyrus (DG) distinguish the DG from other hippocampal subfields (CA1-3) because there are two glutamatergic cell types in the DG rather than one. Thus, in the DG, the main cell types include glutamatergic granule cells (GCs) and MCs, whereas in CA1-3, the only glutamatergic cell type is the pyramidal cell. In contrast to GCs, MCs are different in morphology, intrinsic electrophysiological properties, afferent input and axonal projections, so their function is likely to be very different from GCs...
December 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29218003/eye-drops-for-activation-of-dreadds
#8
William T Keenan, Diego C Fernandez, Lukas J Shumway, Haiqing Zhao, Samer Hattar
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are an important tool for modulating and understanding neural circuits. Depending on the DREADD system used, DREADD-targeted neurons can be activated or repressed in vivo following a dose of the DREADD agonist clozapine-N-oxide (CNO). Because DREADD experiments often involve behavioral assays, the method of CNO delivery is important. Currently, the most common delivery method is intraperitoneal (IP) injection. IP injection is both a fast and reliable technique, but it is painful and stressful particularly when many injections are required...
2017: Frontiers in Neural Circuits
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
#9
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/29180723/neuromodulation-of-orexin-neurons-reduces-diet-induced-adiposity
#10
A N Zink, P E Bunney, A A Holm, C J Billington, C M Kotz
BACKGROUND/OBJECTIVES: Low levels of orexin are associated with obesity and reduced physical activity in humans and animals. SUBJECTS/METHODS: Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated orexin neurons in mouse lateral hypothalamus (LH) to measure effects on spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic injection of AAV vectors into caudal lateral LH of heterozygous orexin Cre or C57/B6J mice...
November 28, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29153928/enhancing-excitability-of-dopamine-neurons-promotes-motivational-behaviour-through-increased-action-initiation
#11
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/29146932/activation-of-endogenous-arginine-vasopressin-neurons-inhibit-food-intake-by-using-a-novel-transgenic-rat-line-with-dreadds-system
#12
Mitsuhiro Yoshimura, Kazuaki Nishimura, Haruki Nishimura, Satomi Sonoda, Hiromichi Ueno, Yasuhito Motojima, Reiko Saito, Takashi Maruyama, Yuki Nonaka, Yoichi Ueta
Various studies contributed to discover novel mechanisms of central arginine vasopressin (AVP) system responsible for the behaviour albeit endogenous vasopressin activation. We established a novel transgenic rat line which expresses both human muscarinic acetylcholine receptors (hM3Dq), of which ligand is clozapine-N-oxide (CNO), and mCherry fluorescence specifically in AVP neurons. The mCherry neurons that indicate the expression of the hM3Dq gene were observed in the suprachiasmatic (SCN), supraoptic (SON), and paraventricular nuclei (PVN)...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120948/parvalbumin-containing-gaba-cells-and-schizophrenia-experimental-model-based-on-targeted-gene-delivery-through-adeno-associated-viruses
#13
Marta U Woloszynowska-Fraser, Peer Wulff, Gernot Riedel
Understanding the contribution of transmitter systems in behavioural pharmacology has a long tradition. Multiple techniques such as transmitter-specific lesions, and also localized administration of pharmacological toxins including agonists and antagonists of selected receptors have been applied. More recently, modern genetic tools have permitted cell-type selective interferences, for example by expression of light-sensitive channels followed by optogenetic stimulation in behaviourally meaningful settings or by engineered channels termed DREADDS that respond to peripherally administered drugs...
December 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29097517/neuropeptides-in-obesity-and-metabolic-disease
#14
REVIEW
Agatha A van der Klaauw
BACKGROUND: The global rise in the prevalence of obesity and associated comorbidities such as type 2 diabetes, cardiovascular disease, and cancer represents a major public health concern. CONTENT: Studies in rodents with the use of global and targeted gene disruption, and mapping of neurocircuitry by using optogenetics and designer receptors exclusively activated by designer drugs (DREADDs) have greatly advanced our understanding of the neural control of body weight...
November 2, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29089872/role-for-the-ventral-posterior-medial-posterior-lateral-thalamus-and-anterior-cingulate-cortex-in-affective-motivation-pain-induced-by-varicella-zoster-virus
#15
Phillip R Kramer, Jennifer Strand, Crystal Stinson, Larry L Bellinger, Paul R Kinchington, Michael B Yee, Mikhail Umorin, Yuan B Peng
Varicella zoster virus (VZV) infects the face and can result in chronic, debilitating pain. The mechanism for this pain is unknown and current treatment is often not effective, thus investigations into the pain pathway become vital. Pain itself is multidimensional, consisting of sensory and affective experiences. One of the primary brain substrates for transmitting sensory signals in the face is the ventral posterior medial/posterior lateral thalamus (VPM/VPL). In addition, the anterior cingulate cortex (ACC) has been shown to be vital in the affective experience of pain, so investigating both of these areas in freely behaving animals was completed to address the role of the brain in VZV-induced pain...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29077837/selective-pharmacogenetic-activation-of-catecholamine-subgroups-in-the-ventrolateral-medulla-elicits-key-glucoregulatory-responses
#16
Ai-Jun Li, Qing Wang, Sue Ritter
Catecholamine (CA) neurons in the ventrolateral medulla (VLM) contribute importantly to glucoregulation during glucose deficit. However, it is not known which CA neurons elicit different glucoregulatory responses or whether selective activation of CA neurons is sufficient to elicit these responses. Therefore, to selectively activate CA subpopulations, we injected male or female Th-Cre+ transgenic rats with the Cre-dependent DREADD construct, AAV2-DIO-hSyn-hM3D(Gq)-mCherry, at one of 4 rostrocaudal levels of the VLM: rostral C1 (C1r), middle C1 (C1m), the area of A1 and C1 overlap (A1/C1) or A1...
October 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/29069598/brain-wide-mapping-of-endogenous-serotonergic-transmission-via-chemogenetic-fmri
#17
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
https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#18
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
No abstract text is available yet for this article.
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29042322/activation-of-parvalbumin-neurons-in-the-rostro-dorsal-sector-of-the-thalamic-reticular-nucleus-promotes-sensitivity-to-pain-in-mice
#19
Jing Liu, Meng-Qi Zhang, Xu Wu, Michael Lazarus, Yoan Cherasse, Mao-Yun Yuan, Zhi-Li Huang, Rui-Xi Li
The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. In our study, the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain regulation was studied using chemogenetics based on designer receptors exclusively activated by designer drugs (DREADD)...
October 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/29037828/chemogenetic-modulation-of-cholinergic-interneurons-reveals-their-regulating-role-on-the-direct-and-indirect-output-pathways-from-the-striatum
#20
Patrick Aldrin-Kirk, Andreas Heuer, Daniella Rylander Ottosson, Marcus Davidsson, Bengt Mattsson, Tomas Björklund
The intricate balance between dopaminergic and cholinergic neurotransmission in the striatum has been thoroughly difficult to characterize. It was initially described as a seesaw with a competing function of dopamine versus acetylcholine. Recent technical advances however, have brought this view into question suggesting that the two systems work rather in concert with the cholinergic interneurons (ChIs) driving dopamine release. In this study, we have utilized two transgenic Cre-driver rat lines, a choline acetyl transferase ChAT-Cre transgenic rat and a novel double-transgenic tyrosine hydroxylase TH-Cre/ChAT-Cre rat to further elucidate the role of striatal ChIs in normal motor function and in Parkinson's disease...
October 14, 2017: Neurobiology of Disease
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