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https://www.readbyqxmd.com/read/28628036/arcuate-neuropeptide-y-inhibits-sympathetic-nerve-activity-via-multiple-neuropathways
#1
Zhigang Shi, Christopher J Madden, Virginia L Brooks
Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH)...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28623920/ketamine-induced-apoptosis-in-the-mouse-cerebral-cortex-follows-similar-characteristic-of-physiological-apoptosis-and-can-be-regulated-by-neuronal-activity
#2
Qi Wang, Feng-Yan Shen, Rong Zou, Jing-Jing Zheng, Xiang Yu, Ying-Wei Wang
The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry...
June 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28609587/chemogenetic-modulation-of-g-protein-coupled-receptor-signalling-in-visual-attention-research
#3
Søren H Jørgensen, Ciarán Martin Fitzpatrick, Ulrik Gether, David D P Woldbye, Andreas T Sørensen
Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attention control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been a major area of investigation, it has proven difficult to accurately associate specific neuronal projections, cell types, neurotransmitter systems and receptors with distinct phenotypes owing to its complexity. In this MiniReview, we present a recently invented technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
June 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28502844/a-novel-approach-to-map-induced-activation-of-neuronal-networks-using-chemogenetics-and-functional-neuroimaging-in-rats-a-proof-of-concept-study-on-the-mesocorticolimbic-system
#4
Theresia J M Roelofs, Jeroen P H Verharen, Geralda A F van Tilborg, Linde Boekhoudt, Annette van der Toorn, Johannes W de Jong, Mieneke C M Luijendijk, Willem M Otte, Roger A H Adan, Rick M Dijkhuizen
Linking neural circuit activation at whole-brain level to neuronal activity at cellular level remains one of the major challenges in neuroscience research. We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic or mesocortical pathways, i...
May 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28498919/chemicogenetic-restoration-of-the-prefrontal-cortex-to-amygdala-pathway-ameliorates-stress-induced-deficits
#5
Jing Wei, Ping Zhong, Luye Qin, Tao Tan, Zhen Yan
Corticosteroid stress hormones exert a profound impact on cognitive and emotional processes. Understanding the neuronal circuits that are altered by chronic stress is important for counteracting the detrimental effects of stress in a brain region- and cell type-specific manner. Using the chemogenetic tool, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the remote, noninvasive and long-lasting modulation of cellular activity and signal transduction in discrete neuronal populations in vivo, we sought to identify the specific pathways that play an essential role in stress responses...
May 11, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-herg-potassium-channel
#6
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome (LQTS). Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
May 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28489327/new-directions-for-the-treatment-of-depression-targeting-the-photic-regulation-of-arousal-and-mood-pram-pathway
#7
REVIEW
Hannah E Bowrey, Morgan H James, Gary Aston-Jones
Both preclinical and clinical studies demonstrate that depression is strongly associated with reduced light availability, which in turn contributes to decreased function of brain regions that control mood. Here, we review findings that support a critical pathway for the control of mood that depends upon ambient light. We put forward a novel hypothesis, functionally linking retina to locus coeruleus (LC) in depression, and discuss the role of norepinephrine in affective disease. Finally, we discuss how utilizing the chemogenetic tool Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to precisely control this retina-LC circuit may be used as a novel therapeutic to treat depression...
May 10, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/28472396/chronic-activation-of-hypothalamic-oxytocin-neurons-improves-cardiac-function-during-left-ventricular-hypertrophy-induced-heart-failure
#8
Kara Garrott, Jhansi Dyavanapalli, Edmund Cauley, Mary Kate Dwyer, Sarah Kuzmiak-Glancy, Xin Wang, David Mendelowitz, Matthew Kay
AIMS: A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. METHODS AND RESULTS: Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF...
May 2, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28461695/a-hippocampus-to-prefrontal-cortex-neural-pathway-inhibits-food-motivation-through-glucagon-like-peptide-1-signaling
#9
T M Hsu, E E Noble, C M Liu, A M Cortella, V R Konanur, A N Suarez, D J Reiner, J D Hahn, M R Hayes, S E Kanoski
The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28451710/thalamic-inputs-to-dorsomedial-striatum-are-involved-in-inhibitory-control-evidence-from-the-five-choice-serial-reaction-time-task-in-rats
#10
Jasjot Saund, Daniel Dautan, Claire Rostron, Gonzalo P Urcelay, Todor V Gerdjikov
RATIONALE: Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. OBJECTIVES: Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats...
April 28, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28425495/the-biglen-gpr171-peptide-receptor-system-within-the-basolateral-amygdala-regulates-anxiety-like-behavior-and-contextual-fear-conditioning
#11
Erin N Bobeck, Ivone Gomes, Darlene Pena, Kirstie A Cummings, Roger L Clem, Mihaly Mezei, Lakshmi A Devi
Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA) play an important role in the pathology of anxiety and other mood disorders. Since GPR171, a recently deorphanized receptor for the abundant neuropeptide BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety-like behaviors. To carry out these studies we identified small molecule ligands using a homology model of GPR171 to virtually screen a library of compounds. One of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells, (ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii) feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons in the arcuate nucleus...
April 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#12
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414301/striatopallidal-dysfunction-underlies-repetitive-behavior-in-shank3-deficient-model-of-autism
#13
Wenting Wang, Chenchen Li, Qian Chen, Marie-Sophie van der Goes, James Hawrot, Annie Y Yao, Xian Gao, Congyi Lu, Ying Zang, Qiangge Zhang, Katherine Lyman, Dongqing Wang, Baolin Guo, Shengxi Wu, Charles R Gerfen, Zhanyan Fu, Guoping Feng
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28413092/resisting-the-urge-to-act-dreadds-modifying-habits-trends-in-neurosciences-40-61-62-2017
#14
M A G Eldridge, B J Richmond
No abstract text is available yet for this article.
May 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28386207/activation-of-the-ventral-tegmental-area-increased-wakefulness-in-mice
#15
Huan-Xin Sun, Dian-Ru Wang, Chen-Bo Ye, Zhen-Zhen Hu, Chen-Yao Wang, Zhi-Li Huang, Su-Rong Yang
The ventral tegmental area (VTA) is crucial for brain functions, such as voluntary movement and cognition; however, the role of VTA in sleep-wake regulation when directly activated or inhibited remains unknown. In this study, we investigated the effects of activation or inhibition of VTA neurons on sleep-wake behavior using the pharmacogenetic "designer receptors exclusively activated by designer drugs (DREADD)" approach. Immunohistochemistry staining was performed to confirm the microinjection sites, and combined with electrophysiological experiments, to determine whether the VTA neurons were activated or inhibited...
2017: Sleep and Biological Rhythms
https://www.readbyqxmd.com/read/28380690/chemogenetic-inhibition-of-pain-neurons-in-a-mouse-model-of-osteoarthritis
#16
Rachel E Miller, Shingo Ishihara, Bula Bhattacharyya, Ada Delaney, Daniela M Menichella, Richard J Miller, Anne-Marie Malfait
OBJECTIVE: To determine the ability of drugs that activate inhibitory G protein-coupled receptors (GPCRs) expressed in peripheral voltage-gated sodium channel 1.8 (NaV 1.8)-positive sensory neurons to control osteoarthritis (OA)-associated pain. METHODS: We used designer receptors exclusively activated by a designer drug (DREADD) technology, which employs engineered GPCRs to activate or inhibit neurons upon binding the synthetic ligand clozapine N-oxide (CNO). NaV 1...
April 5, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28363838/orexin-activation-counteracts-decreases-in-nonexercise-activity-thermogenesis-neat-caused-by-high-fat-diet
#17
P E Bunney, A N Zink, A A Holm, C J Billington, C M Kotz
Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs)...
March 28, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28334356/transient-cell-intrinsic-activity-regulates-the-migration-and-laminar-positioning-of-cortical-projection-neurons
#18
Nicolas Hurni, Marta Kolodziejczak, Ugo Tomasello, Joan Badia, Moritz Jacobshagen, Julien Prados, Alexandre Dayer
Neocortical microcircuits are built during development and require the coordinated assembly of excitatory glutamatergic projection neurons (PNs) into functional networks. Neuronal migration is an essential step in this process. In addition to cell-intrinsic mechanisms, external cues including neurotransmitters regulate cortical neuron migration, suggesting that early activity could influence this process. Here, we aimed to investigate the role of cell-intrinsic activity in migrating PNs in vivo using a designer receptor exclusively activated by a designer drug (DREADD) chemogenetic approach...
May 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28325790/dopamine-terminals-from-the-ventral-tegmental-area-gate-intrinsic-inhibition-in-the-prefrontal-cortex
#19
William C Buchta, Stephen V Mahler, Benjamin Harlan, Gary S Aston-Jones, Arthur C Riegel
Spike frequency adaptation (SFA or accommodation) and calcium-activated potassium channels that underlie after-hyperpolarization potentials (AHP) regulate repetitive firing of neurons. Precisely how neuromodulators such as dopamine from the ventral tegmental area (VTA) regulate SFA and AHP (together referred to as intrinsic inhibition) in the prefrontal cortex (PFC) remains unclear. Using whole cell electrophysiology, we measured intrinsic inhibition in prelimbic (PL) layer 5 pyramidal cells of male adult rats...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#20
Jessica Raper, Ryan D Morrison, J Scott Daniels, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 30, 2017: ACS Chemical Neuroscience
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