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GABA AND Chromone

Albert Quintana, Elisenda Sanz, Wengang Wang, Granville P Storey, Ali D Güler, Matthew J Wanat, Bryan A Roller, Anna La Torre, Paul S Amieux, G Stanley McKnight, Nigel S Bamford, Richard D Palmiter
The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice...
November 2012: Nature Neuroscience
Livio Luongo, Vito de Novellis, Luisa Gatta, Enza Palazzo, Daniela Vita, Francesca Guida, Catia Giordano, Dario Siniscalco, Ida Marabese, Maria De Chiaro, Serena Boccella, Francesca Rossi, Sabatino Maione
Plastic changes in the amygdala and limbic cortex networks have been widely shown in chronic pain. We have here investigated the role of group I metabotropic glutamate receptors (mGluRs) in the basolateral amygdala (BLA) pre-infra-limbic (PL-IL) divisions of the medial prefrontal cortex (mPFC) neuron connections after carrageenan-induced inflammatory pain in the rat. Intra-plantar injection of carrageenan decreased either spontaneous or mechanically/electrically evoked activity of PL cortex pyramidal neurons which responded with excitation in a way prevented by CPCOOEt, a selective mGluR1 antagonist, though not by MPEP, a selective mGluR5 antagonist...
March 2013: Neuropharmacology
Hisako Nakayama, Taisuke Miyazaki, Kazuo Kitamura, Kouichi Hashimoto, Yuchio Yanagawa, Kunihiko Obata, Kenji Sakimura, Masahiko Watanabe, Masanobu Kano
Functional neural circuit formation during development involves massive elimination of redundant synapses. In the cerebellum, one-to-one connection from excitatory climbing fiber (CF) to Purkinje cell (PC) is established by elimination of early-formed surplus CFs. This process depends on glutamatergic excitatory inputs, but contribution of GABAergic transmission remains unclear. Here, we demonstrate impaired CF synapse elimination in mouse models with diminished GABAergic transmission by mutation of a single allele for the GABA synthesizing enzyme GAD67, by conditional deletion of GAD67 from PCs and GABAergic interneurons or by pharmacological inhibition of cerebellar GAD activity...
April 26, 2012: Neuron
Louise Adermark
The frequency and duration of glutamatergic inputs to the striatum are strong determinants of the net effect of retrograde endocannabinoid (eCB) signaling, and key factors in determining if long-term depression (LTD) has a net disinhibitory or inhibitory action in striatum. Low to moderate frequency stimulation in the dorsolateral striatum elevates eCB levels to an extent that primarily depresses transmitter release at inhibitory synapses, leading to a long-lasting disinhibition (DLL) of synaptic output. The aim of this study was to further characterize the basic features of endocannabinoid-mediated DLL of striatal output induced by moderate frequency stimulation (5 Hz, 60 s)...
December 2011: Neuropharmacology
Marion Najac, Didier De Saint Jan, Leire Reguero, Pedro Grandes, Serge Charpak
Olfactory sensory neurons (OSNs) expressing the same odorant receptor converge in specific glomeruli where they transmit olfactory information to mitral cells. Surprisingly, synaptic mechanisms underlying mitral cell activation are still controversial. Using patch-clamp recordings in mouse olfactory bulb slices, we demonstrate that stimulation of OSNs produces a biphasic postsynaptic excitatory response in mitral cells. The response was initiated by a fast and graded monosynaptic input from OSNs and followed by a slower component of feedforward excitation, involving dendro-dendritic interactions between external tufted, tufted and other mitral cells...
June 15, 2011: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Haijun Tu, Chanjuan Xu, Wenhua Zhang, Qiuyao Liu, Philippe Rondard, Jean-Philippe Pin, Jianfeng Liu
The G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) play key roles in cell-cell communication. Several studies revealed important synergisms between these two types of receptors, with some of the actions of either receptor being mediated through transactivation of the other. Among the large GPCR family, GABA(B) receptor is activated by the neurotransmitter GABA, and is expressed in most neurons where it mediates slow and prolonged inhibition of synaptic transmission. Here we show that this receptor is involved in the regulation of life and death decisions of cerebellar granule neurons (CGNs)...
January 13, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
M Taketo, H Matsuda
Group I metabotropic glutamate receptors (mGluRs) are coupled to phosphoinositide hydrolysis, and are thought to modulate neuronal excitability, by mobilizing intracellular Ca(2+). Difference in Ca(2+) mobilization among subclasses of the receptors has been reported, and regarded as a possible cause of variant neuronal modifications. In hippocampal interneurons, several subclasses of mGluRs including mGluR1 and mGluR5 have been immunohistochemically identified. The subclass-specific physiological effects of mGluRs on neuronal transmission in hippocampus, however, have not been fully elucidated...
January 15, 2010: Brain Research Bulletin
Agnes Bonnot, Nikolai Chub, Avinash Pujala, Michael J O'Donovan
To further understand the excitatory effects of motoneurons on spinal network function, we investigated the entrainment of disinhibited rhythms by ventral root (VR) stimulation in the neonatal mouse spinal cord. A brief train of stimuli applied to a VR triggered bursting reliably in 31/32 experiments. The same roots that entrained disinhibited bursting could also produce locomotor-like activity with a similar probability when the network was not disinhibited. The ability of VR stimulation to entrain the rhythm persisted in nicotinic and muscarinic cholinergic antagonists but was blocked by the AMPAR antagonist NBQX...
June 2009: Journal of Neurophysiology
Ya-Yun Wang, Pascal Legendre, Jing Huang, Wen Wang, Sheng-Xi Wu, Yun-Qing Li
The spinal dorsal horn (SDH) is the first step in the integration of primary nociceptive information, which is controlled by the descending serotonin (5-HT) system as well as the principal inhibitory neurotransmitter gamma-aminobutyric acid (GABA). However, the influence exerted by 5-HT on GABA synthesis remains poorly understood. The major pathway for GABA synthesis is the enzymatic decarboxylation of glutamate by glutamic acid decarboxylase (GAD) 65 and 67. In the present research, western blotting results show a time- and dose-dependent enhancement of GAD65 and GAD67 expression induced by 5-HT treatment and a concentration of 100nM 5-HT applied for 3 days is shown to be the optimal condition for maximal expression of GAD67 and a significant expression of GAD65...
December 2008: Journal of Chemical Neuroanatomy
Yuko Sugiyama, Shin-ya Kawaguchi, Tomoo Hirano
Synaptic plasticity has been studied extensively at excitatory synapses, whereas studies on plasticity at GABAergic inhibitory synapses have been limited. In the rat cerebellar cortex, postsynaptic depolarization of a Purkinje neuron (PN) induces long-term potentiation of GABA(A) receptor (GABA(A)R) responsiveness (termed rebound potentiation; RP). Induction of RP requires an increase in intracellular Ca(2+) concentration and resultant activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). We previously reported that GABA(B) receptor (GABA(B)R) activation coupled with depolarization suppresses RP induction by facilitating protein phosphatase 1 (PP-1)-mediated inhibition of CaMKII through down-regulation of cAMP-dependent protein kinase A (PKA) activity...
February 2008: European Journal of Neuroscience
Diego Centonze, Silvia Rossi, Chiara Prosperetti, Valeria Gasperi, Valentina De Chiara, Monica Bari, Anne Tscherter, Fabia Febbraro, Giorgio Bernardi, Mauro Maccarrone
Synaptic transmission in the striatum is regulated by metabotropic glutamate (mGlu) receptors through pre- and postsynaptic mechanisms. We investigated the involvement of mGlu 1 and 5 receptors in the control of both excitatory and inhibitory transmission in the striatum. The mGlu 1 and 5 receptor agonist 3,5-DHPG failed to affect glutamate transmission, while it caused a biphasic effect on GABA transmission, characterized by early increase and late decrease in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from striatal principal neurons...
June 2007: Molecular and Cellular Neurosciences
Izumi Fukunaga, Christopher H Yeo, Andrew M Batchelor
CPCCOEt (7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester) is frequently used to test for the involvement of mGlu1 receptors. Using whole-cell voltage recording from Purkinje cells in slices of rat cerebellum we find that CPCCOEt, at concentrations used to block mGlu1 receptors, causes an enhancement of the climbing fibre response. Application of alternative antagonists with activity at mGlu1 neither mimicked nor occluded the effects of CPCCOEt. Receptor antagonists demonstrated that this non-mGlu1 action of CPCCOEt was not mediated by other mGlu receptors or GABA(B) receptors...
February 2007: Neuropharmacology
Omar Cauli, Marta Llansola, Slaven Erceg, Vicente Felipo
BACKGROUND/AIMS: Patients with hepatic encephalopathy show altered motor function, psychomotor slowing and hypokinesia. The underlying mechanisms remain unclear. This work's aims were: (1) to analyse in rats with chronic liver failure due to portacaval shunt (PCS) the neurochemical alterations in the basal ganglia-thalamus-cortex circuits; (2) to correlate these alterations with those in motor function and (3) to normalize motor activity of PCS rats by pharmacological means. METHODS: Extracellular neurotransmitters levels were analysed by in vivo brain microdialysis...
November 2006: Journal of Hepatology
Kevin D Lominac, Zuzana Kapasova, Reem A Hannun, Cole Patterson, Lawrence D Middaugh, Karen K Szumlinski
Blockade of the mGluR5 subtype of Group 1 metabotropic glutamate receptor (mGluRs) reduces the rewarding effects of ethanol (EtOH), while the effects of mGluR1a blockade remain under-investigated. The present study compared the effects of pretreatment with the mGluR5 antagonist MPEP and the mGluR1a antagonist CPCCPOEt upon behavioral and neurochemical variables associated with EtOH reward in alcohol-preferring C57BL/6J mice. Pretreatment with either antagonist (0-10 mg/kg, IP) dose-dependently reduced measures of EtOH reward in an operant self-administration paradigm and the maximally effective antagonist dose (10 mg/kg) also blocked the expression of EtOH-induced place conditioning, as well as EtOH consumption under 24-h free-access conditions...
November 8, 2006: Drug and Alcohol Dependence
V Coutinho, H Mutoh, T Knöpfel
We report an activity-induced green fluorescence signal observed when mouse cerebellar slices were illuminated with blue light and parallel fibre-Purkinje cell synapses were activated. The optical signal consisted of an initial increase in fluorescence that peaked within 1-2 s after the onset of stimulation, followed by a long lasting (40 s) transient decrease in fluorescence. Single or tetanic electrical stimuli applied to the molecular layer elicited 'beam-shaped' fluorescence changes along the trajectory of parallel fibres...
August 2004: European Journal of Neuroscience
Julien Puyal, Silvarosa Grassi, Cristina Dieni, Adele Frondaroli, Danielle Demêmes, Jaqueline Raymond, Vito Enrico Pettorossi
The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation...
December 1, 2003: Journal of Physiology
Min Wu, Tibor Hajszan, Csaba Leranth, Meenakshi Alreja
Tonic impulse flow in the septohippocampal GABAergic pathway is essential for normal cognitive functioning and is sustained, in part, by acetylcholine (ACh) that is released locally via axon collaterals of septohippocampal cholinergic neurons. Septohippocampal cholinergic neurons degenerate in Alzheimer's disease and other neurodegenerative disorders. While the importance of the muscarinic effects of ACh on septohippocampal GABAergic neurons is well recognized, the nicotinic effects of ACh remain unstudied despite the reported benefits of nicotine on cognitive functioning...
September 2003: European Journal of Neuroscience
Vito de Novellis, Ida Marabese, Enza Palazzo, Francesca Rossi, Liberato Berrino, Luigi Rodella, Rossella Bianchi, Francesco Rossi, Sabatino Maione
In this study, we investigated the effects of group I metabotropic glutamate (mglu) receptor ligands on glutamate and gamma-aminobutyric acid (GABA) extracellular concentrations at the periaqueductal grey level by using in vivo microdialysis. An agonist of group I mglu receptors, (S)-3,5-dihydroxyphenylglycine [(S)-3,5-DHPG, 1 and 2 mM], as well as a selective agonist of mglu(5) receptors, (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 2 and 4 mM), both increased dialysate glutamate and GABA concentrations. 7-(Hydroxyimino)cyclopropa-[b]-chromen-1alpha-carboxylate ethyl ester (CPCCOEt, 1 mM), a selective mglu(1) receptor antagonist, and 2-methyl-6-(phenylethynyl)pyridine (MPEP, 0...
February 21, 2003: European Journal of Pharmacology
Pietro Paolo Sanna, Maurizio Cammalleri, Fulvia Berton, Cindy Simpson, Robert Lutjens, Floyd E Bloom, Walter Francesconi
Several signal transduction pathways have been implicated in the induction of long-term potentiation (LTP), yet the signal transduction mechanisms behind the maintenance-expression phase of LTP are still poorly understood. We investigated the role of phosphatidylinositol 3-kinase (PI3-kinase) in LTP at Schaffer collateral/commissural fiber-CA1 synapses in rat hippocampal slices using biochemical approaches and extracellular electrophysiological recordings. We observed that PI3-kinase activity was induced in the CA1 region during LTP of field EPSPs (fEPSPs) and that two structurally unrelated PI3-kinase inhibitors, LY294002 and wortmannin, abated established LTP, suggesting that PI3-kinase is involved in the maintenance-expression phase of LTP...
May 1, 2002: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
V Neugebauer, F Zinebi, R Russell, J P Gallagher, P Shinnick-Gallagher
G-protein-coupled metabotropic glutamate receptors (mGluRs) are being implicated in various forms of neuroplasticity and CNS disorders. This study examined whether the sensitivities of mGluR agonists are modulated in a distinct fashion in different models of synaptic plasticity, specifically, kindling and chronic cocaine treatment. The influence of kindling and chronic cocaine exposure in vivo was examined in vitro on the modulation of synaptic transmission by group II and III metabotropic glutamate receptors using whole cell voltage-clamp recordings of central amygdala (CeA) neurons...
August 2000: Journal of Neurophysiology
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