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Chemogenetics

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https://www.readbyqxmd.com/read/28218622/activation-of-murine-pre-proglucagon-producing-neurons-reduces-food-intake-and-body-weight
#1
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...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28209737/gaba-cells-in-the-central-nucleus-of-the-amygdala-promote-cataplexy
#2
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
#3
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 14, 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
#4
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
#5
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
#6
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 2, 2017: Neuron
https://www.readbyqxmd.com/read/28124114/activation-of-ventral-tegmental-area-dopamine-neurons-produces-wakefulness-through-dopamine-d2-like-receptors-in-mice
#7
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
#8
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
#9
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...
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
#10
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
https://www.readbyqxmd.com/read/28117842/histamine-h3r-receptor-activation-in-the-dorsal-striatum-triggers-stereotypies-in-a-mouse-model-of-tic-disorders
#11
M Rapanelli, L Frick, V Pogorelov, H Ohtsu, H Bito, C Pittenger
Tic disorders affect ~5% of the population and are frequently comorbid with obsessive-compulsive disorder, autism, and attention deficit disorder. Histamine dysregulation has been identified as a rare genetic cause of tic disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene represent a promising pathophysiologically grounded model. How alterations in the histamine system lead to tics and other neuropsychiatric pathology, however, remains unclear. We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice...
January 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28114293/an-intra-amygdala-circuit-specifically-regulates-social-fear-learning
#12
Robert C Twining, Jaime E Vantrease, Skyelar Love, Mallika Padival, J Amiel Rosenkranz
Adaptive social behavior requires transmission and reception of salient social information. Impairment of this reciprocity is a cardinal symptom of autism. The amygdala is a critical mediator of social behavior and is implicated in social symptoms of autism. Here we found that a specific amygdala circuit, from the lateral nucleus to the medial nucleus (LA-MeA), is required for using social cues to learn about environmental cues that signal imminent threats. Disruption of the LA-MeA circuit impaired valuation of these environmental cues and subsequent ability to use a cue to guide behavior...
January 23, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28113165/controlling-seizures-through-chemogenetics-a-new-technique-may-provide-a-more-precise-way-of-targeting-faulty-circuitry-in-the-brain
#13
Michele Solis
Electricity is the currency of our nervous systems. Thinking and planning, walking and talking, eating and sleeping-all our mental and physical activities are driven by electrical signals moving through the brain. This electrical traffic ebbs and flows in consistent patterns across different brain regions, carrying information from one neuron to the next.
September 2016: IEEE Pulse
https://www.readbyqxmd.com/read/28112685/chemogenetic-stimulation-of-striatal-projection-neurons-modulates-responses-to-parkinson-s-disease-therapy
#14
Cristina Alcacer, Laura Andreoli, Irene Sebastianutto, Johan Jakobsson, Tim Fieblinger, Maria Angela Cenci
Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways' contribution to different motor features using SPN type-specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA-induced dyskinesia (LID mice)...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28104285/resisting-the-urge-to-act-dreadds-modifying-habits
#15
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/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#16
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...
October 29, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#17
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/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#18
Michael C Chen, Ramalingam Vetrivelan, Chun-Ni Guo, Catie Chang, Patrick M Fuller, Jun Lu
Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep...
January 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28073937/activity-of-tachykinin1-expressing-pet1-raphe-neurons-modulates-the-drive-to-breathe
#19
Morgan L Hennessy, Andrea Corcoran, Rachael D Brust, Eugene E Nattie, Susan Dymecki
: Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the 5-HT system, which have borne out in functional studies, including the modulation of distinct facets of homeostatic control. These functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to co-express other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#20
Erin S Calipari, Barbara Juarez, Carole Morel, Deena M Walker, Michael E Cahill, Efrain Ribeiro, Ciorana Roman-Ortiz, Charu Ramakrishnan, Karl Deisseroth, Ming-Hu Han, Eric J Nestler
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug...
January 10, 2017: Nature Communications
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