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GABAB Receptor

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https://www.readbyqxmd.com/read/29317600/altered-avalanche-dynamics-in-a-developmental-nmdar-hypofunction-model-of-cognitive-impairment
#1
Saurav Seshadri, Andreas Klaus, Daniel E Winkowski, Patrick O Kanold, Dietmar Plenz
Disturbed activity patterns in cortical networks contribute to the pathophysiology of schizophrenia (SZ). Several lines of evidence implicate NMDA receptor hypofunction in SZ, and blocking NMDA receptor signaling during early neurodevelopment produces cognitive deficits in rodent models that resemble those seen in schizophrenic patients. However, the altered network dynamics underlying these cognitive impairments largely remain to be characterized, especially at the cellular level. Here, we use in vivo two-photon calcium imaging to describe pathological dynamics, occurring in parallel with cognitive dysfunction, in a developmental NMDA receptor hypofunction model...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29317225/anatomical-recovery-of-the-gabaergic-system-after-a-complete-spinal-cord-injury-in-lampreys
#2
D Romaus-Sanjurjo, S M Valle-Maroto, A Barreiro-Iglesias, B Fernández-López, M C Rodicio
Lampreys recover locomotion spontaneously several weeks after a complete spinal cord injury. Dysfunction of the GABAergic system following SCI has been reported in mammalian models. So, it is of great interest to understand how the GABAergic system of lampreys adapts to the post-injury situation and how this relates to spontaneous recovery. The spinal cord of lampreys contains 3 populations of GABAergic neurons and most of the GABAergic innervation of the spinal cord comes from these local cells. GABAB receptors are expressed in the spinal cord of lampreys and they play important roles in the control of locomotion...
January 6, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29317185/cortical-inhibition-assessed-using-paired-pulse-tms-eeg-is-increased-in-older-adults
#3
George M Opie, Simranjit K Sidhu, Nigel C Rogasch, Michael C Ridding, John G Semmler
BACKGROUND: Alterations in inhibitory processes mediated by gamma-aminobutyric acid type B (GABAB) receptors may contribute to age-related functional impairments. However, investigation of these circuits using conventional paired-pulse transcranial magnetic stimulation (TMS) at long interstimulus intervals (∼100-200ms) have produced conflicting results in older adults, possibly due to the indirect nature of the TMS motor evoked potential (MEP). OBJECTIVE: To utilise electroencephalography and TMS coregistration (TMS-EEG) to more directly assess age-related changes in GABAB-mediated long-interval intracortical inhibition (LICI)...
December 30, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/29311610/interneuron-specific-signaling-evokes-distinctive-somatostatin-mediated-responses-in-adult-cortical-astrocytes
#4
Letizia Mariotti, Gabriele Losi, Annamaria Lia, Marcello Melone, Angela Chiavegato, Marta Gómez-Gonzalo, Michele Sessolo, Serena Bovetti, Angelo Forli, Micaela Zonta, Linda Maria Requie, Iacopo Marcon, Arianna Pugliese, Cécile Viollet, Bernhard Bettler, Tommaso Fellin, Fiorenzo Conti, Giorgio Carmignoto
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABAB receptor-mediated Ca2+ elevations, respectively...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29305121/allosteric-interactions-between-gabab1-subunits-control-orthosteric-binding-sites-occupancy-within-gabab-oligomers
#5
REVIEW
Gregory D Stewart, Laëtitia Comps-Agrar, Lenea Blanc Nørskov-Lauritsen, Jean-Philippe Pin, Julie Kniazeff
The GABAB receptor was the first G protein-coupled receptor identified as an obligate heterodimer. It is composed of two subunits, GABAB1 containing the agonist binding site and GABAB2 responsible for G protein activation. The GABAB receptor was found to associate into larger complexes through GABAB1-GABAB1 interactions, both in transfected cells and in brain membranes. Here we assessed the possible allosteric interactions between GABAB heterodimers by analyzing the effect of mutations located at the putative interface between the extracellular binding domains...
January 2, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29299214/intervention-of-the-gamma-aminobutyric-acid-type-b-receptors-of-the-amygdala-central-nucleus-on-the-sensitivity-of-the-morphine-induced-conditionally-preferred-location-in-wistar-female-rats
#6
Firoozeh Alavian, Saeedeh Ghiasvand, Hedayat Sahraei, Maryam Rafiei-Rad
Background: The amygdala is one of the nerve centers involved in drug reward. It is suggested that the central nucleus of the amygdala (CeA) is involved in morphine dependency. The CeA gamma-aminobutyric acid-ergic (GABAergic) system is a mediator of morphine rewarding effects. In this research, the effects of stimulation or inhibition of CeA GABA type B (GABAB) receptors on sensitization acquisition to morphine-induced reward was evaluated in Wistar female rats using conditioned place preferential (CPP) method...
April 2017: Addiction & Health
https://www.readbyqxmd.com/read/29298431/postsynaptic-gababrs-inhibit-l-type-calcium-channels-and-abolish-long-term-potentiation-in-hippocampal-somatostatin-interneurons
#7
Sam A Booker, Desiree Loreth, Annabelle L Gee, Masahiko Watanabe, Peter C Kind, David J A Wyllie, Ákos Kulik, Imre Vida
Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs). Despite GABABRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29283181/loss-of-constitutive-functional-%C3%AE-aminobutyric-acid-type-a-b-receptor-crosstalk-in-layer-5-pyramidal-neurons-of-human-epileptic-temporal-cortex
#8
Katiuscia Martinello, Miriam Sciaccaluga, Roberta Morace, Addolorata Mascia, Antonietta Arcella, Vincenzo Esposito, Sergio Fucile
OBJECTIVE: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult central nervous system, and profound alterations of GABA receptor functions are linked to temporal lobe epilepsy (TLE). Here we describe the functional relationships between GABA receptors type B (GABAB R) and type A (GABAA R) in human temporal cortex and how TLE affects this aspect of GABAergic signaling. METHODS: Miniature inhibitory postsynaptic currents (mIPSCs) were recorded by patch-clamp techniques from human L5 pyramidal neurons in slices from temporal cortex tissue obtained from surgery...
December 28, 2017: Epilepsia
https://www.readbyqxmd.com/read/29218727/gabaa-and-gabab-receptor-subunit-localization-on-neurochemically-identified-neurons-of-the-human-subthalamic-nucleus
#9
Xi Hua Wu, Jennifer Junru Song, Richard Lewis Maxwell Faull, Henry John Waldvogel
The subthalamic nucleus (STN) is a critical excitatory signaling center within the basal ganglia circuitry. The activity of subthalamic neurons is tightly controlled by upstream inhibitory signaling centers in the basal ganglia. In this study, we used immunohistochemical techniques to firstly, visualize and quantify the STN neurochemical organization based on neuronal markers including parvalbumin (PV), calretinin (CR), SMI-32, and GAD65/67 . Secondly, we characterized the detailed regional, cellular and subcellular expression of GABAA (α1 , α2 , α3 , β2/3 , and γ2 ) and GABAB (R1 and R2) receptor subunits within the normal human STN...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29217836/drug-development-for-neurodevelopmental-disorders-lessons-learned-from-fragile-x-syndrome
#10
REVIEW
Elizabeth M Berry-Kravis, Lothar Lindemann, Aia E Jønch, George Apostol, Mark F Bear, Randall L Carpenter, Jacqueline N Crawley, Aurore Curie, Vincent Des Portes, Farah Hossain, Fabrizio Gasparini, Baltazar Gomez-Mancilla, David Hessl, Eva Loth, Sebastian H Scharf, Paul P Wang, Florian Von Raison, Randi Hagerman, Will Spooren, Sébastien Jacquemont
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches...
December 8, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29212923/response-inhibition-activates-distinct-motor-cortical-inhibitory-processes
#11
John Cirillo, Matthew J Cowie, Hayley J MacDonald, Winston D Byblow
We routinely cancel pre-planned movements that are no longer required. If stopping is forewarned, proactive processes are engaged to selectively decrease motor cortex excitability. However, without advance information there is a non-selective reduction in motor cortical excitability. Here we examine modulation of human primary motor cortex inhibitory networks during response inhibition tasks with informative and uninformative cues using paired-pulse transcranial magnetic stimulation. Long- and short-interval intracortical inhibition (LICI and SICI), indicative of GABAB- and GABAA-receptor mediated inhibition respectively, were examined from motor evoked potentials obtained in task-relevant and task-irrelevant hand muscles when response inhibition was preceded by informative and uninformative cues...
December 6, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29195839/the-ventromedial-hypothalamic-nucleus-plays-an-important-role-in-anxiolytic-like-effect-of-neuropeptide-s
#12
Jin Hong Jiang, Ya Li Peng, Pei Jiang Zhang, Hong Xiang Xue, Zhen He, Xue Ya Liang, M Chang
Neuropeptide S (NPS), the endogenous neuropeptide ligand of NPSR, has been reported to regulate anxiety-related behavior involved in multiple brain regions, including amygdale, locus coeruleus and Barrington's nucleus. However, little research has been conducted on the anxiolytic-like behaviors of NPS on the hypothalamus, which was an important area in defensive behavior. Here, we investigated a role of hypothalamus in anxiolytic-like behaviors of NPS. We found that NPSR protein of mouse distributed mainly in the ventromedial hypothalamus (VMH)...
November 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29194563/cyclic-analogues-of-%C3%AE-conotoxin-vc1-1-inhibit-colonic-nociceptors-and-provide-analgesia-in-a-mouse-model-of-chronic-abdominal-pain
#13
Joel Castro, Luke Grundy, Annemie Deiteren, Andrea M Harrington, Tracey O'Donnell, Jessica Maddern, Jessi Moore, Sonia Garcia-Caraballo, Grigori Y Rychkov, Rilei Yu, Quentin Kaas, David J Craik, David J Adams, Stuart M Brierley
BACKGROUND AND PURPOSE: Patients with Irritable Bowel Syndrome suffer from chronic visceral pain (CVP); however, limited analgesic therapeutic options are currently available. We have shown that α-conotoxin Vc1.1-induced activation of GABAB receptors on the peripheral endings of colonic afferents reduces nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined. EXPERIMENTAL APPROACH: Using ex vivo colonic afferent preparations, we determined the inhibitory actions of cyclized Vc1...
November 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29189554/paraneoplastic-lambert-eaton-myasthenic-syndrome-with-limbic-encephalitis-clinical-correlation-with-the-coexistence-of-anti-vgcc-and-anti-gabab-receptor-antibodies
#14
Jonathan J Cho, James P Wymer
OBJECTIVE: To characterize Lambert-Eaton myasthenic syndrome and limbic encephalitis with coexistent voltage-gated calcium channel (VGCC) antibody and γ-aminobutyric acid (GABA) B receptor antibody. METHODS: Case study. RESULTS: A 57-year-old man presented with 6 months of weakness, unsteadiness, and vision difficulties. Examination revealed proximal weakness and diminished reflexes. Electrodiagnostic study revealed low-amplitude motor potentials and facilitation on high-frequency stimulation...
December 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/29177691/differential-association-of-gabab-receptors-with-their-effector-ion-channels-in-purkinje-cells
#15
Rafael Luján, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis de la Ossa, Bernhard Bettler, Kevin Wickman, Masahiko Watanabe, Ryuichi Shigemoto, Yugo Fukazawa
Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines...
November 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29176000/effects-of-gabab-receptor-activation-on-spatial-cognitive-function-and-hippocampal-neurons-in-rat-models-of-type-2-diabetes-mellitus
#16
Xiao-Jun Cai, Lei Wang, Chun-Mei Hu
This study was conducted with the aim being to investigate the effect GABAB receptor activation plays on spatial cognitive function and hippocampal neurons found in the rat models of type 2 diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats' weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze testing system was performed in order to figure out the spatial cognitive function of these rats...
November 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29171922/less-means-more-the-magnitude-of-synaptic-plasticity-along-the-hippocampal-dorso-ventral-axis-is-inversely-related-to-the-expression-levels-of-plasticity-related-neurotransmitter-receptors
#17
Valentyna Dubovyk, Denise Manahan-Vaughan
The dorsoventral axis of the hippocampus exhibits functional differentiations with regard to (spatial Vs emotional learning) and information retention (rapid encoding Vs long-term storage), as well as its sensitivity to neuromodulation and information received from extrahippocampal structures. The mechanisms that underlie these differentiations remain unclear. Here, we explored neurotransmitter receptor expression along the dorsoventral hippocampal axis and compared hippocampal synaptic plasticity in the CA1 region of the dorsal (DH), intermediate (IH) and ventral hippocampi (VH)...
November 24, 2017: Hippocampus
https://www.readbyqxmd.com/read/29166136/the-gamma-aminobutyric-acid-b-receptor-gabab-encephalitis-clinical-manifestations-and-response-to-immunotherapy
#18
Junzhao Cui, Hui Bu, Junying He, Zeyan Zhao, Weixin Han, Ruiping Gao, Xiaoqing Li, Qing Li, Xiaosu Guo, Yueli Zou
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years)...
December 6, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29163811/impaired-gabab-mediated-presynaptic-inhibition-increases-excitatory-strength-and-alters-short-term-plasticity-in-synapsin-knockout-mice
#19
Pierluigi Valente, Pasqualina Farisello, Flavia Valtorta, Pietro Baldelli, Fabio Benfenati
Synapsins are a family of synaptic vesicle phosphoproteins regulating synaptic transmission and plasticity. SYN1/2 genes are major epilepsy susceptibility genes in humans. Consistently, synapsin I/II/III triple knockout (TKO) mice are epileptic and exhibit severe impairments in phasic and tonic GABAergic inhibition that precede the appearance of the epileptic phenotype. These changes are associated with an increased strength of excitatory transmission that has never been mechanistically investigated. Here, we observed that an identical effect in excitatory transmission could be induced in wild-type (WT) Schaffer collateral-CA1 pyramidal cell synapses by blockade of GABAB receptors (GABABRs)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29143124/the-effect-of-inhibition-on-stimulus-specific-adaptation-in-the-inferior-colliculus
#20
Yaneri A Ayala, Manuel S Malmierca
The inferior colliculus is a center of convergence for inhibitory and excitatory synaptic inputs that may be activated simultaneously by sound stimulation. Stimulus repetition may generate response habituation by changing the efficacy of neuron's synaptic inputs. Specialized IC neurons reduce their response to repetitive tones, but restore their firing when a different and infrequent tone occurs, a phenomenon known as stimulus specific adaptation. Here, using the microiontophoresis technique, we determined the role of GABAA-, GABAB-, and glycinergic receptors in stimulus-specific adaptation (SSA)...
November 15, 2017: Brain Structure & Function
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