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https://www.readbyqxmd.com/read/27924875/gabab-receptor-mediates-opposing-adaptations-of-gaba-release-from-two-types-of-prefrontal-interneurons-after-observational-fear
#1
Lei Liu, Wataru Ito, Alexei Morozov
The observational fear (OF) paradigm in rodents, in which the subject is exposed to a distressed conspecific, elicits contextual fear learning and enhances future passive avoidance learning, which may model certain behavioral traits resulting from traumatic experiences in humans. Because these behaviors affected by the OF, require dorso-medial prefrontal cortex (dmPFC), we searched for synaptic adaptations in dmPFC resulting from OF in mice by recording synaptic responses in dmPFC layer V pyramidal neurons elicited by repeated 5 Hz electrical stimulation of dmPFC layer I, or by optogenetic stimulation of specific interneurons ex vivo one day after OF...
December 7, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27923876/stellate-and-pyramidal-neurons-in-goldfish-telencephalon-respond-differently-to-anoxia-and-gaba-receptor-inhibition
#2
Nariman Hossein-Javaheri, Michael P Wilkie, Wudu E Lado, Leslie T Buck
With oxygen deprivation, the mammalian brain undergoes hyper-activity and neuronal death while this does not occur in the anoxia tolerant goldfish (Carassius auratus). Anoxic survival of the goldfish may rely on neuromodulatory mechanisms to suppress neuronal hyper-excitability. Since γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in brain, we decided to investigate its potential role in suppressing the electrical activity of goldfish telencephalic neurons. Utilizing whole-cell patch-clamp recording we recorded the electrical activities of both excitatory (pyramidal) and inhibitory (stellate) neurons...
December 6, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27917928/renal-denervation-improves-the-baroreflex-and-gaba-system-in-chronic-kidney-disease-induced-hypertension
#3
Hsin-Hung Chen, Pei-Wen Cheng, Wen-Yu Ho, Pei-Jung Lu, Chi-Cheng Lai, Yang-Ming Tseng, Hua-Chang Fang, Gwo-Ching Sun, Michael Hsiao, Chun-Peng Liu, Ching-Jiunn Tseng
Hypertensive rats with chronic kidney disease (CKD) exhibit enhanced gamma-aminobutyric acid (GABA)B receptor function and regulation within the nucleus tractus solitarii (NTS). For CKD with hypertension, renal denervation (RD) interrupts the afferent renal sympathetic nerves, which are connecting to the NTS. The objective of the present study was to investigate how RD improves CKD-induced hypertension. Rats underwent 5/6 nephrectomy for 8 weeks, which induced CKD and hypertension. RD was induced by applying phenol to surround the renal artery in CKD...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916555/adx71943-and-adx71441-novel-positive-allosteric-modulators-of-the-gabab-receptor-with-distinct-central-peripheral-profiles-show-efficacy-in-the-monosodium-iodoacetate-model-of-chronic-osteoarthritis-pain-in-the-rat
#4
Mikhail Kalinichev, Tansy Donovan-Rodriguez, Françoise Girard, Hasnaá Haddouk, Isabelle Royer-Urios, Manfred Schneider, Simon T Bate, Cheryl Marker, James D Pomonis, Sonia Poli
We tested novel positive allosteric modulators (PAMs) of the γ-aminobutyric acid receptor B (GABAB), ADX71943 and ADX71441in the monosodium iodoacetate model of chronic osteoarthritis pain in rats with the objective to delineate the role of peripheral versus central GABAB receptor populations in modulation of chronic pain. Anesthetized Sprague-Dawley rats received an injection of monosodium iodoacetate into the knee and were tested for hyperalgesia starting post-MIA day 14. Effects of compounds on ipsilateral joint compression threshold were evaluated on post-MIA day 14 (after acute treatment), as well as after repeated, daily treatment on days 21 and 28 (ADX71943 only) and were compared to those of celecoxib (30mg/kg, p...
December 1, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27913590/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#5
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an inhibitory postsynaptic potential (IPSP) at low stimulation frequency (0...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27905440/organization-and-functions-of-mglu-and-gabab-receptor-complexes
#6
Jean-Philippe Pin, Bernhard Bettler
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27897671/high-intensity-interval-exercise-promotes-motor-cortex-disinhibition-and-early-motor-skill-consolidation
#7
Ellen L Stavrinos, James P Coxon
Gamma-aminobutyric acid (GABA) inhibition shapes motor cortex output, gates synaptic plasticity in the form of long-term potentiation, and plays an important role in motor learning. Remarkably, recent studies have shown that acute cardiovascular exercise can improve motor memory, but the cortical mechanisms are not completely understood. We investigated whether an acute bout of lower-limb high-intensity interval (HIT) exercise could promote motor memory formation in humans through changes in cortical inhibition within the hand region of the primary motor cortex...
November 29, 2016: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/27894927/the-dynamics-of-gaba-signaling-revelations-from-the-circadian-pacemaker-in-the-suprachiasmatic-nucleus
#8
REVIEW
H Elliott Albers, James C Walton, Karen L Gamble, John K McNeill, Daniel L Hummer
Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extra-cellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors...
November 25, 2016: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/27889489/the-drug-candidate-adx71441-is-a-novel-potent-and-selective-positive-allosteric-modulator-of-the-gabab-receptor-with-a-potential-for-treatment-of-anxiety-pain-and-spasticity
#9
Mikhail Kalinichev, Françoise Girard, Hasnaà Haddouk, Mélanie Rouillier, Eric Riguet, Isabelle Royer-Urios, Vincent Mutel, Robert Lütjens, Sonia Poli
Positive allosteric modulation of the GABAB receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27876620/the-gabab-positive-allosteric-modulators-cgp7930-and-gs39783-stimulate-erk1-2-signalling-in-cells-lacking-functional-gabab-receptors
#10
Maria C Olianas, Simona Dedoni, Pierluigi Onali
The present study shows that the GABAB positive allosteric modulators (PAMs) CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signalling in cells that do not express functional GABAB receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a time- and concentration-dependent increase in ERK1/2 phosphorylation with potencies similar to those displayed as GABAB PAMs. Conversely, γ-aminobutyric acid and the GABAB receptor agonists (-)baclofen and SKF97541 were completely inactive...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27867349/baclofen-protects-primary-rat-retinal-ganglion-cells-from-chemical-hypoxia-induced-apoptosis-through-the-akt-and-perk-pathways
#11
Pingping Fu, Qiang Wu, Jianyan Hu, Tingting Li, Fengjuan Gao
Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27862283/footshock-induced-plasticity-of-gabab-signalling-in-the-lateral-habenula-requires-dopamine-and-glucocorticoid-receptors
#12
Salvatore Lecca, Massimo Trusel, Manuel Mameli
The activity of lateral habenula (LHb) represents a substrate for the encoding of negative-valenced events. The exposure to aversive stimuli in naïve mice is sufficient to trigger a reduction in GABAB -mediated signaling in the LHb. This is ultimately instrumental for the hyperactivity of LHb neurons and for the establishment of depressive-like phenotypes. However, the mechanisms responsible for the induction of this aversion-driven plasticity are missing. Using ex-vivo patch-clamp recordings in slices, here we show that exposing mice to a series of inescapable footshocks (FsE) rapidly reduces baclofen-mediated GABAB currents in the LHb...
November 10, 2016: Synapse
https://www.readbyqxmd.com/read/27834391/hippocampal-gabab-1a-receptors-constrain-generalized-contextual-fear
#13
Joseph F Lynch, Patrick Winiecki, T Lee Gilman, Jordan M Adkins, Aaron M Jasnow
Many anxiety disorders are characterized by generalization of fear responses to neutral or ambiguous stimuli. Therefore, a comprehensive understanding of the mechanisms contributing to generalized fear is essential for formulating successful treatments for anxiety disorders. Previous research shows that GABA-mediated presynaptic inhibition plays a critical role in cued fear generalization, as animals with genetically deleted presynaptic GABAB(1a) receptors cannot discriminate between CS+ and CS- tones. Work from our lab has further identified that GABAB(1a) receptors are necessary for maintaining contextual memory precision, thereby constraining generalized contextual fear...
November 11, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27822602/interhemispheric-regulation-of-the-rat-medial-prefrontal-cortical-glutamate-stress-response-role-of-local-gaba-and-dopamine-sensitive-mechanisms
#14
Derek Lupinsky, Luc Moquin, Alain Gratton
RATIONALE: We previously reported that stressors increase medial prefrontal cortex (PFC) glutamate (GLU) levels as a result of activating callosal neurons located in the opposite hemisphere and that this PFC GLU stress response is regulated by GLU-, dopamine- (DA-), and GABA-sensitive mechanisms (Lupinsky et al. 2010). OBJECTIVES: Here, we examine the possibility that PFC DA regulates the stress responsivity of callosal neurons indirectly by acting at D1 and D2 receptors located on GABA interneurons...
November 7, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27821575/vasculo-neuronal-coupling-retrograde-vascular-communication-to-brain-neurons
#15
Ki Jung Kim, Juan Ramiro Diaz, Jennifer A Iddings, Jessica A Filosa
: Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined if flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone which result in arteriole constriction and dilation, respectively altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel-to-astrocyte-to neuron, a direction opposite to that of classic neurovascular coupling and referred here as vasculo-neuronal coupling (VNC)...
November 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27812916/gabab-receptors-as-modulating-target-for-inflammatory-responses-of-the-periodontal-ligament
#16
Anna Konermann, Thomas Van Dyke, Alpdogan Kantarci, Andreas Jäger
PDL cells express GABAB1 and GABAB2 receptors, which are regulated by inflammation and thus might be implicated in periodontal immunology. It was the aim of this study to elucidate the functional role of GABAB receptors in immunomodulation regarding activation of proregenerative versus proinflammatory mechanisms. Human PDL cells were exposed to GABA and/or GABAB receptor antagonist CGP-52432 alone or in combination with IL-1β to mimic inflammation. The influence on marker expression for inflammatory tissue destruction was determined via qRT-PCR and Luminex assays...
November 3, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27781034/generalized-epilepsy-and-myoclonic-seizures-in-22q11-2-deletion-syndrome
#17
Vincent Strehlow, Marielle E M Swinkels, Rhys H Thomas, Nora Rapps, Steffen Syrbe, Thomas Dorn, Johannes R Lemke
Prompted by the observations of juvenile myoclonic epilepsy (JME) in 22q11.2 deletion syndrome (22q11DS) and recurrent copy number variants in genetic generalized epilepsy (GGE), we searched for further evidence supporting a possible correlation of 22q11DS with GGE and with myoclonic seizures. Through routine diagnostics, we identified 3 novel individuals with the seemingly uncommon combination of 22q11DS and JME. We subsequently screened the literature for reports focussing on the epilepsy phenotype in 22q11DS...
September 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27731803/effect-of-gabab-receptor-antagonists-cgp-35348-and-cgp-55845-on-serum-interleukin-6-and-18-concentrations-in-albino-mice-following-neonatal-hypoxia-ischemia-insult
#18
Quratulane Gillani, Muhammad Ali, Furhan Iqbal
Interleukin (IL) 6 and 18 plays an important role in inflammatory response following hypoxia ischemia encephalopathy (HIE). Present study was designed to demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845), respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia encephalopathy on postnatal day 10 (right common carotid artery was ligated followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following weaning, mice were divided in three groups, in gender specific manner, and fed on normal rodent diet till they were 13 week old...
September 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27717812/behavioural-endophenotypes-in-mice-lacking-the-auxiliary-gabab-receptor-subunit-kctd16
#19
Flurin Cathomas, Hannes Sigrist, Luca Schmid, Erich Seifritz, Martin Gassmann, Bernhard Bettler, Christopher R Pryce
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABAB receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABAB receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12(-/-)) exhibit increased auditory fear learning and that Kctd12(+/-) mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons...
October 4, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27703268/optogenetic-activation-of-septal-gabaergic-afferents-entrains-neuronal-firing-in-the-medial-habenula
#20
Kyuhyun Choi, Youngin Lee, Changwoo Lee, Seokheon Hong, Soonje Lee, Shin Jung Kang, Ki Soon Shin
The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (γ -aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner...
October 5, 2016: Scientific Reports
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