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https://www.readbyqxmd.com/read/28325790/dopamine-terminals-from-the-ventral-tegmental-area-gate-intrinsic-inhibition-in-the-prefrontal-cortex
#1
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
#2
Jessica Raper, J Scott Daniels, Ryan D Morrison, 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 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28322236/the-role-of-mesolimbic-reward-neurocircuitry-in-prevention-and-rescue-of-the-activity-based-anorexia-aba-phenotype-in-rats
#3
Claire J Foldi, Laura K Milton, Brian J Oldfield
Patients suffering anorexia nervosa (AN) become anhedonic; unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia (ABA) model recapitulates many of the characteristics of the human condition, including anhedonia, and allows investigation of the underlying neurobiology of AN. The potential for increased neuronal activity in reward/hedonic circuits to prevent and rescue weight loss is investigated in this model. The mesolimbic pathway extending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) was activated using a dual viral strategy, involving retrograde transport of Cre (CAV2-Cre) to the VTA and coincident injection of DREADD receptors (AAV-hSyn-DIO-hM3D(Gq)-mCherry)...
March 21, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28321131/does-activation-of-midbrain-dopamine-neurons-promote-or-reduce-feeding
#4
L Boekhoudt, T J M Roelofs, J W de Jong, A E de Leeuw, M C M Luijendijk, I G Wolterink-Donselaar, G van der Plasse, R A H Adan
BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake...
March 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28281681/chemogenetic-stimulation-of-the-hypoglossal-neurons-improves-upper-airway-patency
#5
Thomaz Fleury Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, Luiz U Sennes, Luu V Pham, Ellen E Ladenheim, Richard Spencer, David Mendelowitz, Alan R Schwartz, Vsevolod Y Polotsky
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#6
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28257896/orexin-2-receptor-regulation-of-the-hypothalamic-pituitary-adrenal-hpa-response-to-acute-and-repeated-stress
#7
Laura A Grafe, Darrell Eacret, Sandra Luz, Anthony L Gotter, John J Renger, Chris J Winrow, Seema Bhatnagar
Orexins are hypothalamic neuropeptides that have a documented role in mediating the acute stress response. However, their role in habituation to repeated stress, and the role of orexin receptors (OX1R and OX2R) in the stress response, has yet to be defined. Orexin neuronal activation and levels in the cerebrospinal fluid (CSF) were found to be stimulated with acute restraint, but were significantly reduced by day five of repeated restraint. As certain disease states such as panic disorder are associated with increased central orexin levels and failure to habituate to repeated stress, the effect of activating orexin signaling via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on the hypothalamic-pituitary-adrenal (HPA) response was evaluated after repeated restraint...
February 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28244163/chemogenetic-enhancement-of-functional-recovery-after-a-sciatic-nerve-injury
#8
Poonam B Jaiswal, Arthur W English
Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools used to modulate neuronal excitability. We hypothesized that activation of excitatory (Gq) DREADD by its designer ligand, clozapine-N-oxide (CNO), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (LG) muscle of adult female Lewis rats was injected unilaterally with AAV9- hsyn- hM3Dq-mCherry (7...
February 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28235898/gabaergic-neurons-of-the-central-amygdala-promote-cataplexy
#9
Carrie E Mahoney, Lindsay J Agostinelli, Jessica N K Brooks, Bradford B Lowell, Thomas E Scammell
Narcolepsy is characterized by chronic sleepiness and cataplexy - sudden muscle paralysis triggered by strong, positive emotions. Narcolepsy is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. As GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy...
February 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28218623/dreadding-proglucagon-neurons-a-fresh-look-at-metabolic-regulation-by-the-brain
#10
Jonathan E Campbell, David A D'Alessio
Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, the stimuli that activate GCG+ neurons are not well known, which has made understanding the role of this neuronal population in the CNS a challenge. In this issue of the JCI, Gaykema et al. use designer receptors exclusively activated by designer drugs (DREADD) technology to specifically activate GCG+ neurons in mouse models...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28193686/paraventricular-thalamus-balances-danger-and-reward
#11
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/28176786/disrupted-glutamatergic-transmission-in-prefrontal-cortex-contributes-to-behavioral-abnormality-in-an-animal-model-of-adhd
#12
Jia Cheng, Aiyi Liu, Michael Y Shi, Zhen Yan
Spontaneously hypertensive rats (SHR) are the most widely used animal model for the study of attention deficit hyperactivity disorder (ADHD). Here we sought to reveal the neuronal circuits and molecular basis of ADHD and its potential treatment using SHR. Combined electrophysiological, biochemical, pharmacological, chemicogenetic and behavioral approaches were utilized. We found that AMPAR-mediated synaptic transmission in pyramidal neurons of prefrontal cortex (PFC) was diminished in SHR, which was correlated with the decreased surface expression of AMPAR subunits...
February 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28167604/gs-dreadd-knock-in-mice-for-tissue-specific-temporal-stimulation-of-camp-signaling
#13
Dmitry Akhmedov, Maria G Mendoza-Rodriguez, Kavitha Rajendran, Mario Rossi, Jürgen Wess, Rebecca Berdeaux
Hundreds of hormones and ligands stimulate cAMP signaling in different tissues through activation of G protein-coupled receptors (GPCRs). Although functions and individual effectors of cAMP signaling are well characterized in many tissues, pleiotropic effects of GPCR agonists limit investigation of physiologic functions of cAMP signaling in individual cell types at different developmental stages in vivo To facilitate studies of cAMP signaling in specific cell populations in vivo, we harnessed the power of DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology by creating ROSA26-based knock-in mice for conditional expression of a Gs-coupled DREADD (rM3Ds-GFP, or "GsD")...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28138563/ganglionic-gfap-glial-gq-gpcr-signaling-enhances-heart-functions-in-vivo
#14
Alison Xiaoqiao Xie, Jakovin J Lee, Ken D McCarthy
The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP(+)) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP(+) glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28106041/glutamatergic-projections-from-the-entorhinal-cortex-to-dorsal-dentate-gyrus-mediate-context-induced-reinstatement-of-heroin-seeking
#15
Feifei Ge, Na Wang, Cailian Cui, Yijing Li, Yan Liu, Yaoying Ma, Shuli Liu, Haolin Zhang, Xiaowei Sun
Re-exposure to the context associated with heroin intake provokes relapse to drug taking after abstinence. The dorsal dentate gyrus (dDG) and entorhinal cortex (EC) have been implicated in contextual memory processing, but the underlying circuit mechanisms in context-induced relapse remains poorly understood. In this study, using a self-administration rat model, we found that activation and synaptic transmission of glutamatergic projections from the EC to the upper blade of dentate gyrus (dDGub) were significantly enhanced during context-induced reinstatement of heroin seeking...
January 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28104285/resisting-the-urge-to-act-dreadds-modifying-habits
#16
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/28094035/extinction-generates-outcome-specific-conditioned-inhibition
#17
Vincent Laurent, Billy Chieng, Bernard W Balleine
Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions...
December 5, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#18
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...
April 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#19
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/28053227/a-hypothalamic-circuit-that-controls-body-temperature
#20
Zheng-Dong Zhao, Wen Z Yang, Cuicui Gao, Xin Fu, Wen Zhang, Qian Zhou, Wanpeng Chen, Xinyan Ni, Jun-Kai Lin, Juan Yang, Xiao-Hong Xu, Wei L Shen
The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD)...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
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