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https://www.readbyqxmd.com/read/27890661/studying-brain-regulation-of-immunity-with-optogenetics-and-chemogenetics-a-new-experimental-platform
#1
REVIEW
Tamar Ben-Shaanan, Maya Schiller, Asya Rolls
The interactions between the brain and the immune system are bidirectional. Nevertheless, we have far greater understanding of how the immune system affects the brain than how the brain affects immunity. New technological developments such as optogenetics and chemogenetics (using DREADDs; Designer Receptors Exclusively Activated by Designer Drugs) can bridge this gap in our understanding, as they enable an unprecedented mechanistic and systemic analysis of the communication between the brain and the immune system...
November 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27866960/ethanol-seeking-behavior-is-expressed-directly-through-an-extended-amygdala-to-midbrain-neural-circuit
#2
Melanie M Pina, Christopher L Cunningham
Abstinent alcohol-dependent individuals experience an enduring sensitivity to cue-induced craving and relapse to drinking. There is considerable evidence indicating that structures within the midbrain and extended amygdala are involved in this process. Individually, the ventral tegmental area (VTA) and the bed nucleus of the stria terminalis (BNST) have been shown to modulate cue-induced ethanol-seeking behavior. It is hypothesized that cue-induced seeking is communicated through a direct projection from the BNST to VTA...
November 17, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27822508/clozapine-n-oxide-administration-produces-behavioral-effects-in-long-evans-rats-implications-for-designing-dreadd-experiments
#3
Duncan A A MacLaren, Richard W Browne, Jessica K Shaw, Sandhya Krishnan Radhakrishnan, Prachi Khare, Rodrigo A España, Stewart D Clark
Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des)...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27798132/gi-dreadd-expression-in-peripheral-nerves-produces-ligand-dependent-analgesia-as-well-as-ligand-independent-functional-changes-in-sensory-neurons
#4
Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold
: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27767183/molecular-characterization-of-thy1-expressing-fear-inhibiting-neurons-within-the-basolateral-amygdala
#5
Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27759104/single-and-transient-ca-2-peaks-in-podocytes-do-not-induce-changes-in-glomerular-filtration-and-perfusion
#6
Sybille Koehler, Sebastian Brähler, Alexander Kuczkowski, Julia Binz, Matthias J Hackl, Henning Hagmann, Martin Höhne, Merly C Vogt, Claudia M Wunderlich, F Thomas Wunderlich, Frank Schweda, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27733612/sustained-gq-protein-signaling-disrupts-striatal-circuits-via-jnk
#7
Luigi Bellocchio, Andrea Ruiz-Calvo, Anna Chiarlone, Magali Cabanas, Eva Resel, Jean-René Cazalets, Cristina Blázquez, Yoon H Cho, Ismael Galve-Roperh, Manuel Guzmán
: The dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the Gs/Gi-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of Gq-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of Gq-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca(2+)/proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27721502/calcium-dysregulation-contributes-to-neurodegeneration-in-ftld-patient-ipsc-derived-neurons
#8
Keiko Imamura, Naruhiko Sahara, Nicholas M Kanaan, Kayoko Tsukita, Takayuki Kondo, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada, Koichi Kawakami, Akitsu Hotta, Satoshi Yawata, Dai Watanabe, Masato Hasegawa, John Q Trojanowski, Virginia M-Y Lee, Tetsuya Suhara, Makoto Higuchi, Haruhisa Inoue
Mutations in the gene MAPT encoding tau, a microtubules-associated protein, cause a subtype of familial neurodegenerative disorder, known as frontotemporal lobar degeneration tauopathy (FTLD-Tau), which presents with dementia and is characterized by atrophy in the frontal and temporal lobes of the brain. Although induced pluripotent stem cell (iPSC) technology has facilitated the investigation of phenotypes of FTLD-Tau patient neuronal cells in vitro, it remains unclear how FTLD-Tau patient neurons degenerate...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27712862/chemogenetic-activation-of-dopamine-neurons-in-the-ventral-tegmental-area-but-not-substantia-nigra-induces-hyperactivity-in-rats
#9
Linde Boekhoudt, Azar Omrani, Mieneke C M Luijendijk, Inge G Wolterink-Donselaar, Ellen C Wijbrans, Geoffrey van der Plasse, Roger A H Adan
Hyperactivity is a core symptom in various psychiatric disorders, including attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and anorexia nervosa. Although hyperactivity has been linked to dopaminergic signalling, the causal relationship between midbrain dopamine neuronal activity and locomotor hyperactivity remains unknown. In this study, we test whether increased dopamine neuronal activity is sufficient to induce locomotor hyperactivity. To do so, we used designer receptors exclusively activated by designer drugs (DREADD) to chemogenetically enhance neuronal activity in two main midbrain dopamine neuron populations, i...
October 3, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27707965/basal-ganglia-output-controls-active-avoidance-behavior
#10
Sebastian Hormigo, German Vega-Flores, Manuel A Castro-Alamancos
: Engrained avoidance behavior is highly adaptive when it keeps away harmful events and can be highly maladaptive when individuals elude harmless situations in anxiety disorders, but the neural circuits that mediate avoidance are poorly understood. Using DREADDs and optogenetics in mice, we show that the output of the basal ganglia through the substantia nigra pars reticulata (SNr) controls active avoidance. SNr excitation blocks avoidance to a conditioned sensory stimulus while preserving the ability to escape the harmful event...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27696530/stimulation-induced-transient-changes-in-neuronal-activity-blood-flow-and-n-acetylaspartate-content-in-rat-prefrontal-cortex-a-chemogenetic-fmrs-bold-study
#11
Morris H Baslow, Christopher K Cain, Robert Sears, Donald A Wilson, Alvin Bachman, Scott Gerum, David N Guilfoyle
Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA...
December 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27688998/defining-a-novel-leptin-melanocortin-kisspeptin-pathway-involved-in-the-metabolic-control-of-puberty
#12
Maria Manfredi-Lozano, Juan Roa, Francisco Ruiz-Pino, Richard Piet, David Garcia-Galiano, Rafael Pineda, Aurora Zamora, Silvia Leon, Miguel A Sanchez-Garrido, Antonio Romero-Ruiz, Carlos Dieguez, Maria Jesus Vazquez, Allan E Herbison, Leonor Pinilla, Manuel Tena-Sempere
OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27683912/chemogenetic-activation-of-an-extinction-neural-circuit-reduces-cue-induced-reinstatement-of-cocaine-seeking
#13
Isabel F Augur, Andrew R Wyckoff, Gary Aston-Jones, Peter W Kalivas, Jamie Peters
UNLABELLED: The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27658900/changes-in-female-drosophila-sleep-following-mating-are-mediated-by-spsn-sag-neurons
#14
David S Garbe, Abigail S Vigderman, Emilia Moscato, Abigail E Dove, Christopher G Vecsey, Matthew S Kayser, Amita Sehgal
Female Drosophila melanogaster, like many other organisms, exhibit different behavioral repertoires after mating with a male. These postmating responses (PMRs) include increased egg production and laying, increased rejection behavior (avoiding further male advances), decreased longevity, altered gustation and decreased sleep. Sex Peptide (SP), a protein transferred from the male during copulation, is largely responsible for many of these behavioral responses, and acts through a specific circuit to induce rejection behavior and alter dietary preference...
September 22, 2016: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/27639988/pharmacogenetic-reactivation-of-the-original-engram-evokes-an-extinguished-fear-memory
#15
Takahiro Yoshii, Hiroshi Hosokawa, Naoki Matsuo
Fear memory extinction has several characteristic behavioral features, such as spontaneous recovery, renewal, and reinstatement, suggesting that extinction training does not erase the original association between the conditioned stimulus (CS) and the unconditioned stimulus (US). However, it is unclear whether reactivation of the original physical record of memory (i.e., memory trace) is sufficient to produce conditioned fear response after extinction. Here, we performed pharmacogenetic neuronal activation using transgenic mice expressing hM3Dq DREADD (designer receptor exclusively activated by designer drug) under the control of the activity-dependent c-fos gene promoter...
September 14, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27605603/resolving-behavioral-output-via-chemogenetic-designer-receptors-exclusively-activated-by-designer-drugs
#16
C Joseph Burnett, Michael J Krashes
Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying behavioral outputs. They exhibit a number of advantages: they rely on cell-specific manipulations through canonical intracellular signaling pathways, they are easy and cost-effective to implement in a laboratory setting, and they are easily scalable for single-region or full-brain manipulations. On the other hand, DREADDs rely on ligand-G-protein-coupled receptor interactions, leading to coarse temporal dynamics...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27477013/a-powerful-dreadd-revealing-structural-drivers-of-functional-dynamics
#17
Ankit N Khambhati, Danielle S Bassett
In this issue of Neuron, Grayson et al. (2016) report how inhibition of amygdala impacts amygdalocortical and corticocortical functional connectivity. Their study predicts changes in functional brain topology, induced by pharmacologic modulation of neuroanatomical circuits using designer receptors exclusively activated by designer drugs (DREADDs), through virtual lesioning of amygdala in structural brain networks.
July 20, 2016: Neuron
https://www.readbyqxmd.com/read/27461895/deciphering-and-modulating-g-protein-signalling-in-c-elegans-using-the-dreadd-technology
#18
Simone Prömel, Franziska Fiedler, Claudia Binder, Jana Winkler, Torsten Schöneberg, Doreen Thor
G-protein signalling is an evolutionary conserved concept highlighting its fundamental impact on developmental and functional processes. Studies on the effects of G protein signals on tissues as well as an entire organism are often conducted in Caenorhabditis elegans. To understand and control dynamics and kinetics of the processes involved, pharmacological modulation of specific G protein pathways would be advantageous, but is difficult due to a lack in accessibility and regulation. To provide this option, we designed G protein-coupled receptor-based designer receptors (DREADDs) for C...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27461084/constitutive-and-acquired-serotonin-deficiency-alters-memory-and-hippocampal-synaptic-plasticity
#19
Sebastian P Fernandez, Aude Muzerelle, Sophie Scotto-Lomassese, Jacques Barik, Agnès Gruart, José M Delgado-García, Patricia Gaspar
Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory, and underlying mechanisms, has not been established. We used mice with a constitutive depletion of 5-HT brain levels, (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning or fear memory...
July 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27422019/parvalbumin-interneurons-constrain-the-size-of-the-lateral-amygdala-engram
#20
Dano J Morrison, Asim J Rashid, Adelaide P Yiu, Chen Yan, Paul W Frankland, Sheena A Josselyn
Memories are thought to be represented by discrete physiological changes in the brain, collectively referred to as an engram, that allow patterns of activity present during learning to be reactivated in the future. During the formation of a conditioned fear memory, a subset of principal (excitatory) neurons in the lateral amygdala (LA) are allocated to a neuronal ensemble that encodes an association between an initially neutral stimulus and a threatening aversive stimulus. Previous experimental and computational work suggests that this subset consists of only a small proportion of all LA neurons, and that this proportion remains constant across different memories...
July 12, 2016: Neurobiology of Learning and Memory
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