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https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#1
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer's disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies...
September 25, 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
#2
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 14, 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
#3
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 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28976945/activation-of-nigrostriatal-dopamine-neurons-during-fear-extinction-prevents-the-renewal-of-fear
#4
Courtney A Bouchet, Megan A Miner, Esteban C Loetz, Adam J Rosberg, Holly S Hake, Caroline E Farmer, Mykola Ostrovskyy, Nathan Gray, Benjamin N Greenwood
Manipulations that increase dopamine (DA) signaling can enhance fear extinction, but the circuits involved remain unknown. DA neurons originating in the substantia nigra (SN) projecting to the dorsal striatum (DS) are traditionally viewed in the context of motor behavior, but growing data implicate this nigrostriatal circuit in emotion. Here we investigated the role of nigrostriatal DA in fear extinction. Activation of SN DA neurons with designer Gq-coupled receptors exclusively activated by designer drugs (Gq-DREADD) during fear extinction had no effect on fear extinction acquisition, but enhanced fear extinction memory and blocked the renewal of fear in a novel context; a pattern of data paralleled by cFos expression in the central amygdala...
October 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28926549/chemical-methods-dreadds-see-no-cno
#5
Mirella Bucci
No abstract text is available yet for this article.
September 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28912160/dopamine-d2-receptors-modulate-pyramidal-neurons-in-mouse-medial-prefrontal-cortex-through-a-stimulatory-g-protein-pathway
#6
Sarah E Robinson, Vikaas S Sohal
Dopaminergic modulation of prefrontal cortex (PFC) is thought to play key roles in many cognitive functions and to be disrupted in pathological conditions, such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically projecting (SC) pyramidal neurons within L5 of the PFC. These D2R-induced ADPs only occur following synaptic input, which activates NMDARs, even when the delay between the synaptic input and ADPs is relatively long (e...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28900892/increased-locus-coeruleus-tonic-activity-causes-disengagement-from-a-patch-foraging-task
#7
Gary A Kane, Elena M Vazey, Robert C Wilson, Amitai Shenhav, Nathaniel D Daw, Gary Aston-Jones, Jonathan D Cohen
High levels of locus coeruleus (LC) tonic activity are associated with distraction and poor performance within a task. Adaptive gain theory (AGT; Aston-Jones & Cohen, 2005) suggests that this may reflect an adaptive function of the LC, encouraging search for more remunerative opportunities in times of low utility. Here, we examine whether stimulating LC tonic activity using designer receptors (DREADDs) promotes searching for better opportunities in a patch-foraging task as the value of a patch diminishes. The task required rats to decide repeatedly whether to exploit an immediate but depleting reward within a patch or to incur the cost of a time delay to travel to a new, fuller patch...
September 12, 2017: Cognitive, Affective & Behavioral Neuroscience
https://www.readbyqxmd.com/read/28831138/embryonic-hindbrain-patterning-genes-delineate-distinct-cardio-respiratory-and-metabolic-homeostatic-populations-in-the-adult
#8
Jenny J Sun, Teng-Wei Huang, Jeffrey L Neul, Russell S Ray
Previous studies based on mouse genetic mutations suggest that proper partitioning of the hindbrain into transient, genetically-defined segments called rhombomeres is required for normal respiratory development and function in neonates. Less clear is what role these genes and the neurons they define play in adult respiratory circuit organization. Several Cre drivers are used to access and study developmental rhombomeric domains (Eng1 (Cre) , HoxA2-Cre, Egr2 (Cre) , HoxB1 (Cre) , and HoxA4-Cre) in the adult...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830762/contribution-of-amygdala-crf-neurons-to-chronic-pain
#9
Matthew Andreoli, Tanvi Marketkar, Eugene Dimitrov
We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord...
August 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28794102/optogenetics-and-pharmacogenetics-principles-and-applications
#10
Jingwei Jiang, Huxing Cui, Kamal Rahmouni
Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin and archaerhodopsins) from the bacteria has made it possible to utilize light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G-protein coupled receptors which can be activated by otherwise inert drug-like small molecules such as the Designer Receptors Exclusively Activated by Designer Drug (DREADD) - a form of chemogenetics...
August 9, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28774929/chemogenetics-revealed-dreadd-occupancy-and-activation-via-converted-clozapine
#11
Juan L Gomez, Jordi Bonaventura, Wojciech Lesniak, William B Mathews, Polina Sysa-Shah, Lionel A Rodriguez, Randall J Ellis, Christopher T Richie, Brandon K Harvey, Robert F Dannals, Martin G Pomper, Antonello Bonci, Michael Michaelides
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency...
August 4, 2017: Science
https://www.readbyqxmd.com/read/28752052/the-role-of-ghrelin-responsive-mediobasal-hypothalamic-neurons-in-mediating-feeding-responses-to-fasting
#12
Bharath K Mani, Sherri Osborne-Lawrence, Mathieu Mequinion, Sydney Lawrence, Laurent Gautron, Zane B Andrews, Jeffrey M Zigman
OBJECTIVE: Ghrelin is a stomach-derived hormone that affects food intake and regulates blood glucose. The best-characterized actions of ghrelin are mediated by its binding to and activation of the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Adequate examination of the identity, function, and relevance of specific subsets of GHSR-expressing neurons has been hampered by the absence of a suitable Cre recombinase (Cre)-expressing mouse line with which to manipulate gene expression in a targeted fashion within GHSR-expressing neurons...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28716712/effects-of-chemogenetic-excitation-or-inhibition-of-the-ventrolateral-periaqueductal-gray-on-the-acquisition-and-extinction-of-pavlovian-fear-conditioning
#13
Carolyn Arico, Elena E Bagley, Pascal Carrive, Neda Assareh, Gavan P McNally
The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses. It is less clear whether the PAG regulates fear learning when other measures of learned fear are used...
July 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28684394/tg-th-cre-fi172gsat-th-cre-defines-neurons-that-are-required-for-full-hypercapnic-and-hypoxic-reflexes
#14
Jenny J Sun, Russell S Ray
The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat (Th-Cre)-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREADD-mediated inhibition of Th-Cre-defined neurons results in blunted ventilatory responses under respiratory challenge...
August 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28680103/chemogenetic-silencing-of-gabaergic-dorsal-horn-interneurons-induces-morphine-resistant-spontaneous-nocifensive-behaviours
#15
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677202/dreadd-induced-silencing-of-the-medial-amygdala-reduces-the-preference-for-male-pheromones-and-the-expression-of-lordosis-in-estrous-female-mice
#16
Elizabeth A McCarthy, Arman Maqsudlu, Matthew Bass, Sofia Georghiou, James A Cherry, Michael J Baum
Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28673934/activation-of-sf1-neurons-in-the-ventromedial-hypothalamus-by-dreadd-technology-increases-insulin-sensitivity-in-peripheral-tissues
#17
Eulalia A Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen-Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi
The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology...
September 2017: Diabetes
https://www.readbyqxmd.com/read/28664926/memory-retention-involves-the-ventrolateral-orbitofrontal-cortex-comparison-with-the-basolateral-amygdala
#18
K S Zimmermann, C Li, D G Rainnie, K J Ressler, S L Gourley
The orbitofrontal cortex (OFC) is thought to link stimuli and actions with anticipated outcomes in order to sustain flexible behavior in an ever-changing environment. How it retains these associations to guide future behavior is less well-defined. Here we focused on one subregion of this heterogeneous structure, the ventrolateral OFC (VLO). CaMKII-driven inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were infused and subsequently activated by their ligand Clozapine-N-oxide (CNO) in conjunction with fear extinction training (a form of aversive conditioning) and response-outcome conditioning (a form of appetitive conditioning)...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28664636/chemogenetic-inhibition-reveals-midline-thalamic-nuclei-and-thalamo-accumbens-projections-mediate-cocaine-seeking-in-rats
#19
Amanda M Wunsch, Lindsay M Yager, Elizabeth A Donckels, Calvin T Le, John F Neumaier, Susan M Ferguson
Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of how this circuit regulates drug-seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical-basal ganglia-thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28628036/arcuate-neuropeptide-y-inhibits-sympathetic-nerve-activity-via-multiple-neuropathways
#20
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 30, 2017: Journal of Clinical Investigation
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