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https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#1
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/28317132/chemogenetic-versus-recombination-driven-manipulation-of-enteric-glia
#2
Werend Boesmans, Pieter Vanden Berghe
Gastrointestinal function depends on the integrated activity of neurons and glia of the enteric nervous system (ENS). This article is protected by copyright. All rights reserved.
March 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28297715/autism-gene-ube3a-and-seizures-impair-sociability-by-repressing-vta-cbln1
#3
Vaishnav Krishnan, David C Stoppel, Yi Nong, Mark A Johnson, Monica J S Nadler, Ekim Ozkaynak, Brian L Teng, Ikue Nagakura, Fahim Mohammad, Michael A Silva, Sally Peterson, Tristan J Cruz, Ekkehard M Kasper, Ramy Arnaout, Matthew P Anderson
Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant type of autism linked to increased gene dosages of UBE3A, which encodes a ubiquitin ligase with transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the nucleus downregulates the glutamatergic synapse organizer Cbln1, which is needed for sociability in mice. Epileptic seizures also repress Cbln1 and are found to expose sociability impairments in mice with asymptomatic increases in UBE3A...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28294135/bidirectional-control-of-anxiety-related-behaviours-in-mice-role-of-inputs-arising-from-the-ventral-hippocampus-to-the-lateral-septum-and-medial-prefrontal-cortex
#4
Gustavo Morrone Parfitt, Robin Nguyen, Jee Yoon Bang, Afif Aqrabawi, Matthew M Tran, D Kanghoon Seo, Blake A Richards, Jun Chul Kim
Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioural contribution at circuit level...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28287401/prostaglandin-mediated-inhibition-of-serotonin-signaling-controls-the-affective-component-of-inflammatory-pain
#5
Anand Kumar Singh, Joanna Zajdel, Elahe Mirrasekhian, Nader Almoosawi, Isabell Frisch, Anna M Klawonn, Maarit Jaarola, Michael Fritz, David Engblom
Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E2 that is synthesized by cyclooxygenase 2 in neural cells...
March 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28281681/chemogenetic-stimulation-of-the-hypoglossal-neurons-improves-upper-airway-patency
#6
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/28279562/neural-circuit-mechanisms-underlying-emotional-regulation-of-homeostatic-feeding
#7
REVIEW
Patrick Sweeney, Yunlei Yang
The neural circuits controlling feeding and emotional behaviors are intricately and reciprocally connected. Recent technological developments, including cell type-specific optogenetic and chemogenetic approaches, allow functional characterization of genetically defined cell populations and neural circuits in feeding and emotional processes. Here we review recent studies that have utilized circuit-based manipulations to decipher the functional interactions between neural circuits controlling feeding and those controlling emotional processes...
March 6, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#8
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/28244163/chemogenetic-enhancement-of-functional-recovery-after-a-sciatic-nerve-injury
#9
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/28238201/advances-in-optogenetic-and-chemogenetic-methods-to-study-brain-circuits-in-non-human-primates
#10
REVIEW
Adriana Galvan, Michael J Caiola, Daniel L Albaugh
Over the last 10 years, the use of opto- and chemogenetics to modulate neuronal activity in research applications has increased exponentially. Both techniques involve the genetic delivery of artificial proteins (opsins or engineered receptors) that are expressed on a selective population of neurons. The firing of these neurons can then be manipulated using light sources (for opsins) or by systemic administration of exogenous compounds (for chemogenetic receptors). Opto- and chemogenetic tools have enabled many important advances in basal ganglia research in rodent models, yet these techniques have faced a slow progress in non-human primate (NHP) research...
February 25, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28218622/activation-of-murine-pre-proglucagon-producing-neurons-reduces-food-intake-and-body-weight
#11
Ronald P Gaykema, Brandon A Newmyer, Matteo Ottolini, Vidisha Raje, Daniel M Warthen, Philip S Lambeth, Maria Niccum, Ting Yao, Yiru Huang, Ira G Schulman, Thurl E Harris, Manoj K Patel, Kevin W Williams, Michael M Scott
Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28209737/gaba-cells-in-the-central-nucleus-of-the-amygdala-promote-cataplexy
#12
Matthew B Snow, Jimmy J Fraigne, Gabrielle Thibault-Messier, Victoria L Chuen, Aren Thomasian, Richard L Horner, John Peever
Cataplexy is a hallmark of narcolepsy characterized by the sudden uncontrollable onset of muscle weakness or paralysis during wakefulness. It can occur spontaneously, but is typically triggered by positive emotions such as laughter. Although cataplexy was identified over 130 years ago, its neural mechanism remains unclear. Here, we show that a newly identified GABA circuit within the central nucleus of the amygdala (CeA) promotes cataplexy. We used behavioral, electrophysiological, immunohistochemical, and chemogenetic strategies to selectively target and manipulate CeA activity in narcoleptic (orexin(-/-) ) mice to determine its functional role in controlling cataplexy...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28196880/agrp-to-kiss1-neuron-signaling-links-nutritional-state-and-fertility
#13
Stephanie L Padilla, Jian Qiu, Casey C Nestor, Chunguang Zhang, Arik W Smith, Benjamin B Whiddon, Oline K Rønnekleiv, Martin J Kelly, Richard D Palmiter
Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1(AVPV), and arcuate hypothalamus, Kiss1(ARH)), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193686/paraventricular-thalamus-balances-danger-and-reward
#14
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/28175426/179%C3%A2-chemogenetic-stimulation-of-the-lumbar-locomotor-network-enhances-motor-function-following-experimental-cervical-spinal-cord-injury-translational-relevance-for-a-novel-therapeutic-strategy
#15
Spyridon K Karadimas, Kajana Satkunendrarajah, Michael G Fehlings
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28162807/a-brainstem-spinal-cord-inhibitory-circuit-for-mechanical-pain-modulation-by-gaba-and-enkephalins
#16
Amaury François, Sarah A Low, Elizabeth I Sypek, Amelia J Christensen, Chaudy Sotoudeh, Kevin T Beier, Charu Ramakrishnan, Kimberly D Ritola, Reza Sharif-Naeini, Karl Deisseroth, Scott L Delp, Robert C Malenka, Liqun Luo, Adam W Hantman, Grégory Scherrer
Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28124114/activation-of-ventral-tegmental-area-dopamine-neurons-produces-wakefulness-through-dopamine-d2-like-receptors-in-mice
#17
Yo Oishi, Yoshiaki Suzuki, Koji Takahashi, Toshiya Yonezawa, Takeshi Kanda, Yohko Takata, Yoan Cherasse, Michael Lazarus
A growing body of evidence suggests that dopamine plays a role in sleep-wake regulation, but the dopamine-producing brain areas that control sleep-wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep-wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation...
January 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28123032/role-of-dorsomedial-striatum-neuronal-ensembles-in-incubation-of-methamphetamine-craving-after-voluntary-abstinence
#18
Daniele Caprioli, Marco Venniro, Michelle Zhang, Jennifer M Bossert, Brandon L Warren, Bruce T Hope, Yavin Shaham
We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123013/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#19
Jasper A Heinsbroek, Daniela N Neuhofer, William C Griffin, Griffin S Siegel, Ana-Clara Bobadilla, Yonatan M Kupchik, Peter W Kalivas
Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123012/accumbens-nnos-interneurons-regulate-cocaine-relapse
#20
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Constanza Garcia-Keller, Neringa M Stankeviciute, Rachel J Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine seeking result from glutamate spillover, initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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