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Chemogenetics

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https://www.readbyqxmd.com/read/29903974/reactivation-of-recall-induced-neurons-contributes-to-remote-fear-memory-attenuation
#1
Ossama Khalaf, Siegfried Resch, Lucie Dixsaut, Victoire Gorden, Liliane Glauser, Johannes Gräff
Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found-chemogenetically and in an engram-specific manner-that effective remote fear attenuation is accompanied by the reactivation of memory recall-induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction...
June 15, 2018: Science
https://www.readbyqxmd.com/read/29897332/orbital-frontal-cortex-updates-state-induced-value-change-for-decision-making
#2
Emily T Baltz, Ege A Yalcinbas, Rafael Renteria, Christina M Gremel
Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC's contribution to goal-directed or model-based behavior, where the decision to act is controlled by previous experience with the consequence or outcome. Investigating OFC's role in learning about changed outcomes separate from decision-making is not trivial and often the two are confounded. Here we adapted an incentive learning task to mice, where we investigated processes controlling experience-based outcome updating independent from inferred action control...
June 13, 2018: ELife
https://www.readbyqxmd.com/read/29896090/activation-of-dorsomedial-hypothalamic-neurons-promotes-physical-activity-and-decreases-food-intake-and-body-weight-in-zucker-fatty-rats
#3
Ni Zhang, Liang Yang, Lanting Guo, Sheng Bi
Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker ( Lepr(fa) , ZF) and Koletsky ( Lepr(fak) , SHROB) rats...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29878108/impaired-melanocortin-pathway-function-in-prader-willi-syndrome-gene-magel2-deficient-mice
#4
Merve Oncul, Pelin Dilsiz, Edanur Ates Oz, Tayfun Ates, Iltan Aklan, Esref Celik, Nilufer Sayar Atasoy, Deniz Atasoy
Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder causing social and learning deficits, impaired satiety and severe childhood obesity. Genetic underpinning of PWS involves deletion of a chromosomal region with several genes, including MAGEL2, which is abundantly expressed in the hypothalamus. Of appetite regulating hypothalamic cell types, both AGRP and POMC-expressing neurons contain Magel2 transcripts but the functional impact of its deletion on these cells has not been fully characterized. Here, we investigated these key neurons in Magel2-null mice in terms of the activity levels at different energy states as well as their behavioral function...
June 5, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29878069/differential-contributions-of-glutamatergic-hippocampal%C3%A2-retrosplenial-cortical-projections-to-the-formation-and-persistence-of-context-memories
#5
Naoki Yamawaki, Kevin A Corcoran, Anita L Guedea, Gordon M G Shepherd, Jelena Radulovic
Learning to associate stressful events with specific environmental contexts depends on excitatory transmission in the hippocampus, but how this information is transmitted to the neocortex for lasting memory storage is unclear. We identified dorsal hippocampal (DH) projections to the retrosplenial cortex (RSC), which arise mainly from the subiculum and contain either the vesicular glutamate transporter 1 (vGlut1) or vGlut2. Both vGlut1+ and vGlut2+ axons strongly excite and disynaptically inhibit RSC pyramidal neurons in superficial layers, but vGlut2+ axons trigger greater inhibition that spreads to deep layers, indicating that these pathways engage RSC circuits via partially redundant, partially differentiated cellular mechanisms...
June 6, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29875446/chemogenetic-activation-of-ventral-tegmental-area-gaba-neurons-but-not-mesoaccumbal-gaba-terminals-disrupts-responding-to-reward-predictive-cues
#6
Ken T Wakabayashi, Malte Feja, Ajay N Baindur, Michael J Bruno, Rohan V Bhimani, Jinwoo Park, Kathryn Hausknecht, Roh-Yu Shen, Samir Haj-Dahmane, Caroline E Bass
Cues predicting rewards can gain motivational properties and initiate reward-seeking behaviors. Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are critical in regulating cue-motivated responding. Although, approximately one third of mesoaccumbal projection neurons are GABAergic, it is unclear how this population influences motivational processes and cue processing. This is largely due to our inability to pharmacologically probe circuit level contributions of VTA-GABA, which arises from diverse sources, including multiple GABA afferents, interneurons, and projection neurons...
May 22, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29867371/pv-interneurons-critical-regulators-of-e-i-balance-for-prefrontal-cortex-dependent-behavior-and-psychiatric-disorders
#7
REVIEW
Brielle R Ferguson, Wen-Jun Gao
Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV) GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses...
2018: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29861386/control-of-feeding-behavior-by-cerebral-ventricular-volume-transmission-of-melanin-concentrating-hormone
#8
Emily E Noble, Joel D Hahn, Vaibhav R Konanur, Ted M Hsu, Stephen J Page, Alyssa M Cortella, Clarissa M Liu, Monica Y Song, Andrea N Suarez, Caroline C Szujewski, Danielle Rider, Jamie E Clarke, Martin Darvas, Suzanne M Appleyard, Scott E Kanoski
Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons...
May 15, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29844415/regulation-of-cortical-activity-and-arousal-by-the-matrix-cells-of-the-ventromedial-thalamic-nucleus
#9
Sakiko Honjoh, Shuntaro Sasai, Shannon S Schiereck, Hirotaka Nagai, Giulio Tononi, Chiara Cirelli
The "non-specific" ventromedial thalamic nucleus (VM) has long been considered a candidate for mediating cortical arousal due to its diffuse, superficial projections, but direct evidence was lacking. Here, we show in mice that the activity of VM calbindin1-positive matrix cells is high in wake and REM sleep and low in NREM sleep, and increases before cortical activity at the sleep-to-wake transition. Optogenetic stimulation of VM cells rapidly awoke all mice from NREM sleep and consistently caused EEG activation during slow wave anesthesia, while arousal did not occur from REM sleep...
May 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29812985/remote-control-of-glucose-sensing-neurons-to-analyze-glucose-metabolism
#10
Alexandra Alvarsson, Sarah A Stanley
The central nervous system relies on a continual supply of glucose, and must be able to detect glucose levels and regulate peripheral organ functions to ensure that its energy requirements are met. Specialized glucose-sensing neurons, first described half a century ago, use glucose as a signal and modulate their firing rates as glucose levels change. Glucose excited neurons are activated by increasing glucose concentrations while glucose inhibited neurons increase their firing rate with falling glucose concentrations and decrease their firing rate as glucose concentrations rise...
May 29, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29804835/astrocytic-activation-generates-de-novo-neuronal-potentiation-and-memory-enhancement
#11
Adar Adamsky, Adi Kol, Tirzah Kreisel, Adi Doron, Nofar Ozeri-Engelhard, Talia Melcer, Ron Refaeli, Henrike Horn, Limor Regev, Maya Groysman, Michael London, Inbal Goshen
Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased...
May 18, 2018: Cell
https://www.readbyqxmd.com/read/29786639/chemogenetic-enhancement-of-axon-regeneration-following-peripheral-nerve-injury-in-the-slick-a-mouse
#12
Poonam B Jaiswal, Olivia C Mistretta, Patricia J Ward, Arthur W English
The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre-recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i...
May 22, 2018: Brain Sciences
https://www.readbyqxmd.com/read/29780165/a-medial-prefrontal-cortex-nucleus-acumens-corticotropin-releasing-factor-circuitry-for-neuropathic-pain-increased-susceptibility-to-opioid-reward
#13
Yuanzhong Kai, Yanhua Li, Tingting Sun, Weiwei Yin, Yu Mao, Jie Li, Wen Xie, Shi Chen, Likui Wang, Juan Li, Zhi Zhang, Wenjuan Tao
Recent studies have shown that persistent pain facilitates the response to morphine reward. However, the circuit mechanism underlying this process remains ambiguous. In this study, using chronic constriction injury (CCI) of the sciatic nerve in mice, we found that persistent neuropathic pain reduced the minimum number of morphine conditioning sessions required to induce conditioned place preference (CPP) behavior. This dose of morphine had no effect on the pain threshold. In the medial prefrontal cortex (mPFC), which is involved in both pain and emotion processing, corticotropin-releasing factor (CRF) expressing neuronal activity was increased in CCI mice...
May 21, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29778899/dopamine-loss-alters-the-hippocampus-nucleus-accumbens-synaptic-transmission-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#14
Alberto Cordella, Paraskevi Krashia, Annalisa Nobili, Annabella Pignataro, Livia La Barbera, Maria Teresa Viscomi, Alessandro Valzania, Flavio Keller, Martine Ammassari-Teule, Nicola Biagio Mercuri, Nicola Berretta, Marcello D'Amelio
The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD...
August 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29772198/the-map-and-the-territory-mapping-the-territory-regulated-by-serotonergic-signaling-at-striatal-projection-neurons
#15
Andrew F Scheyer, Olivier J Manzoni
In this issue of Neuron, Cavaccini et al. (2018) identify and thoroughly describe a previously unknown role for hyper-localized serotonergic signaling in the modulation of striatal projection neuron plasticity using electrophysiological, chemogenetic, and optogenetic approaches in addition to advanced imaging technology.
May 16, 2018: Neuron
https://www.readbyqxmd.com/read/29769699/a-stocked-toolbox-for-understanding-the-role-of-astrocytes-in-disease
#16
REVIEW
Akshata Almad, Nicholas J Maragakis
Our understanding of astrocytes and their role in neurological diseases has increased considerably over the past two decades as the diverse roles of these cells have become recognized. Our evolving understanding of these cells suggests that they are more than support cells for neurons and that they play important roles in CNS homeostasis under normal conditions, in neuroprotection and in disease exacerbation. These multiple functions make them excellent candidates for targeted therapies to treat neurological disorders...
May 16, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29766048/phasic-stimulation-of-midbrain-dopamine-neuron-activity-reduces-salt-consumption
#17
Eleanor C Sandhu, Anushka B P Fernando, Elaine E Irvine, Kyoko Tossell, Michelle Kokkinou, Justyna Glegola, Mark A Smith, Oliver D Howes, Dominic J Withers, Mark A Ungless
Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29754898/replay-of-episodic-memories-in-the-rat
#18
Danielle Panoz-Brown, Vishakh Iyer, Lawrence M Carey, Christina M Sluka, Gabriela Rajic, Jesse Kestenman, Meredith Gentry, Sydney Brotheridge, Isaac Somekh, Hannah E Corbin, Kjersten G Tucker, Bianca Almeida, Severine B Hex, Krysten D Garcia, Andrea G Hohmann, Jonathon D Crystal
Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay...
April 21, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29735555/genetic-activation-inactivation-and-deletion-reveal-a-limited-and-nuanced-role-for-somatostatin-containing-basal-forebrain-neurons-in-behavioral-state-control
#19
Christelle Anaclet, Roberto De Luca, Anne Venner, Olga Malyshevskaya, Michael Lazarus, Elda Arrigoni, Patrick M Fuller
Recent studies have identified an especially important role for basal forebrain GABAergic (BFVGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BFVGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BFVGAT neurons (BFParv and BFSOM ), and it was recently reported that optogenetic activation of BFSOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period...
May 7, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29724954/piezo2-channel-merkel-cell-signaling-modulates-the-conversion-of-touch-to-itch
#20
Jing Feng, Jialie Luo, Pu Yang, Junhui Du, Brian S Kim, Hongzhen Hu
The somatosensory system relays many signals ranging from light touch to pain and itch. Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis...
May 4, 2018: Science
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