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[PMID]: 28867550 [Au] Autor: Dulcis D; Lippi G; Stark CJ; Do LH; Berg DK; Spitzer NC [Ad] Endereço: Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits and Behavior, Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, CA 92093-0357, USA; Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 9209 [Ti] Título: Neurotransmitter Switching Regulated by miRNAs Controls Changes in Social Preference. [So] Source: Neuron;95(6):1319-1333.e5, 2017 Sep 13. [Is] ISSN: 1097-4199 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Changes in social preference of amphibian larvae result from sustained exposure to kinship odorants. To understand the molecular and cellular mechanisms of this neuroplasticity, we investigated the effects of olfactory system activation on neurotransmitter (NT) expression in accessory olfactory bulb (AOB) interneurons during development. We show that protracted exposure to kin or non-kin odorants changes the number of dopamine (DA)- or gamma aminobutyric acid (GABA)-expressing neurons, with corresponding changes in attraction/aversion behavior. Changing the relative number of dopaminergic and GABAergic AOB interneurons or locally introducing DA or GABA receptor antagonists alters kinship preference. We then isolate AOB microRNAs (miRs) differentially regulated across these conditions. Inhibition of miR-375 and miR-200b reveals that they target Pax6 and Bcl11b to regulate the dopaminergic and GABAergic phenotypes. The results illuminate the role of NT switching governing experience-dependent social preference. VIDEO ABSTRACT. [Mh] Termos MeSH primário: Comportamento de Escolha/fisiologia Dopamina/biossíntese MicroRNAs/fisiologia Neurotransmissores/biossíntese Bulbo Olfatório/metabolismo Comportamento Social Ácido gama-Aminobutírico/biossíntese [Mh] Termos MeSH secundário: Animais Dopamina/fisiologia Antagonistas de Dopamina/farmacologia Antagonistas GABAérgicos/farmacologia Interneurônios/fisiologia MicroRNAs/antagonistas & inibidores MicroRNAs/metabolismo Neurônios/metabolismo Neurônios/fisiologia Neurotransmissores/fisiologia Fator de Transcrição PAX6/fisiologia Feromônios/fisiologia Irmãos Fatores de Transcrição/fisiologia Proteínas de Xenopus/fisiologia Xenopus laevis Ácido gama-Aminobutírico/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; VIDEO-AUDIO MEDIA [Nm] Nome de substância: 0 (Bcl11b protein, Xenopus); 0 (Dopamine Antagonists); 0 (GABA Antagonists); 0 (MicroRNAs); 0 (Neurotransmitter Agents); 0 (PAX6 Transcription Factor); 0 (Pax6 protein, Xenopus); 0 (Pheromones); 0 (Transcription Factors); 0 (Xenopus Proteins); 56-12-2 (gamma-Aminobutyric Acid); VTD58H1Z2X (Dopamine) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171003 [Lr] Data última revisão: 171003 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170905 [St] Status: MEDLINE

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[PMID]: 28857763 [Au] Autor: Ma C; Pejo E; McGrath M; Jayakar SS; Zhou X; Miller KW; Cohen JB; Raines DE [Ad] Endereço: From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (C.M., E.P., M.M., X.Z., K.W.M., D.E.R.); and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts (S.S.J., J.B.C.). [Ti] Título: Competitive Antagonism of Anesthetic Action at the γ-Aminobutyric Acid Type A Receptor by a Novel Etomidate Analog with Low Intrinsic Efficacy. [So] Source: Anesthesiology;127(5):824-837, 2017 Nov. [Is] ISSN: 1528-1175 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: The authors characterized the γ-aminobutyric acid type A receptor pharmacology of the novel etomidate analog naphthalene-etomidate, a potential lead compound for the development of anesthetic-selective competitive antagonists. METHODS: The positive modulatory potencies and efficacies of etomidate and naphthalene-etomidate were defined in oocyte-expressed α1ß3γ2L γ-aminobutyric acid type A receptors using voltage clamp electrophysiology. Using the same technique, the ability of naphthalene-etomidate to reduce currents evoked by γ-aminobutyric acid alone or γ-aminobutyric acid potentiated by etomidate, propofol, pentobarbital, and diazepam was quantified. The binding affinity of naphthalene-etomidate to the transmembrane anesthetic binding sites of the γ-aminobutyric acid type A receptor was determined from its ability to inhibit receptor photoaffinity labeling by the site-selective photolabels [H]azi-etomidate and R-[H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid. RESULTS: In contrast to etomidate, naphthalene-etomidate only weakly potentiated γ-aminobutyric acid-evoked currents and induced little direct activation even at a near-saturating aqueous concentration. It inhibited labeling of γ-aminobutyric acid type A receptors by [H]azi-etomidate and R-[H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid with similar half-maximal inhibitory concentrations of 48 µM (95% CI, 28 to 81 µM) and 33 µM (95% CI, 20 to 54 µM). It also reduced the positive modulatory actions of anesthetics (propofol > etomidate ~ pentobarbital) but not those of γ-aminobutyric acid or diazepam. At 300 µM, naphthalene-etomidate increased the half-maximal potentiating propofol concentration from 6.0 µM (95% CI, 4.4 to 8.0 µM) to 36 µM (95% CI, 17 to 78 µM) without affecting the maximal response obtained at high propofol concentrations. CONCLUSIONS: Naphthalene-etomidate is a very low-efficacy etomidate analog that exhibits the pharmacology of an anesthetic competitive antagonist at the γ-aminobutyric acid type A receptor. [Mh] Termos MeSH primário: Ligação Competitiva/fisiologia Etomidato/análogos & derivados Etomidato/metabolismo Antagonistas GABAérgicos/metabolismo Receptores de GABA-A/metabolismo [Mh] Termos MeSH secundário: Animais Ligação Competitiva/efeitos dos fármacos Relação Dose-Resposta a Droga Etomidato/farmacologia Feminino Antagonistas GABAérgicos/farmacologia Naftalenos/química Naftalenos/metabolismo Naftalenos/farmacologia Oócitos Resultado do Tratamento Xenopus laevis Ácido gama-Aminobutírico/metabolismo Ácido gama-Aminobutírico/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (GABA Antagonists); 0 (Naphthalenes); 0 (Receptors, GABA-A); 2166IN72UN (naphthalene); 56-12-2 (gamma-Aminobutyric Acid); Z22628B598 (Etomidate) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171026 [Lr] Data última revisão: 171026 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170901 [St] Status: MEDLINE [do] DOI: 10.1097/ALN.0000000000001840

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[PMID]: 28833036 [Au] Autor: Nemes AD; O'Dwyer R; Najm IM; Ying Z; Gonzalez-Martinez J; Alexopoulos AV [Ad] Endereço: Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, U.S.A. [Ti] Título: Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia. [So] Source: Epilepsia;58(10):1755-1761, 2017 Oct. [Is] ISSN: 1528-1167 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. METHODS: Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA ) antagonist used to provoke generalized seizures as a "second hit." RESULTS: LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. SIGNIFICANCE: Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. [Mh] Termos MeSH primário: Acetamidas/farmacologia Anticonvulsivantes/farmacologia Malformações do Desenvolvimento Cortical/fisiopatologia Convulsões/fisiopatologia [Mh] Termos MeSH secundário: Animais Eletroencefalografia Feminino Antagonistas GABAérgicos/toxicidade Malformações do Desenvolvimento Cortical/etiologia Pentilenotetrazol/toxicidade Piracetam/análogos & derivados Piracetam/farmacologia Gravidez Efeitos Tardios da Exposição Pré-Natal Exposição à Radiação/efeitos adversos Ratos Ratos Sprague-Dawley Convulsões/induzido quimicamente [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Acetamides); 0 (Anticonvulsants); 0 (GABA Antagonists); 230447L0GL (etiracetam); 563KS2PQY5 (lacosamide); WM5Z385K7T (Pentylenetetrazole); ZH516LNZ10 (Piracetam) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170824 [St] Status: MEDLINE [do] DOI: 10.1111/epi.13856

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[PMID]: 28762469 [Au] Autor: Vendramin Pasquetti M; Meier L; Loureiro S; Ganzella M; Junges B; Barbieri Caus L; Umpierrez Amaral A; Koeller DM; Goodman S; Woontner M; Gomes de Souza DO; Wajner M; Calcagnotto ME [Ad] Endereço: Postgraduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. [Ti] Título: Impairment of GABAergic system contributes to epileptogenesis in glutaric acidemia type I. [So] Source: Epilepsia;58(10):1771-1781, 2017 Oct. [Is] ISSN: 1528-1167 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVES: Glutaric acidemia type I (GA-I) is an inherited neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ-aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak. In this work, we evaluated the role of the GABAergic system on epileptogenesis in GA-I using the Gcdh mice exposed to a high lysine diet (Gcdh -Lys). METHODS: Spontaneous recurrent seizures (SRS), seizure susceptibility, and changes in brain oscillations were evaluated by video-electroencephalography (EEG). Cortical GABAergic synaptic transmission was evaluated using electrophysiologic and neurochemical approaches. RESULTS: SRS were observed in 72% of Gcdh -Lys mice, whereas no seizures were detected in age-matched controls (Gcdh or Gcdh receiving normal diet). The severity and number of PTZ-induced seizures were higher in Gcdh -Lys mice. EEG spectral analysis showed a significant decrease in theta and gamma oscillations and predominant delta waves in Gcdh -Lys mice, associated with increased EEG left index. Analysis of cortical synaptosomes revealed a significantly increased percentage of glutamate release and decreased GABA release in Gcdh -Lys mice that were associated with a decrease in cortical GAD immunocontent and activity and confirmed by reduced frequency of inhibitory events in cortical pyramidal cells. SIGNIFICANCE: Using an experimental model with a phenotype similar to that of GA-I in humans-the Gcdh mice under high lysine diet (Gcdh -Lys)-we provide evidence that a reduction in cortical inhibition of Gcdh -Lys mice, probably induced by GAD dysfunction, leads to hyperexcitability and increased slow oscillations associated with neurologic abnormalities in GA-I. Our findings offer a new perspective on the pathophysiology of brain damage in GA-I. [Mh] Termos MeSH primário: Erros Inatos do Metabolismo dos Aminoácidos/genética Encefalopatias Metabólicas/genética Encéfalo/efeitos dos fármacos Epilepsia/genética Glutaril-CoA Desidrogenase/deficiência Glutaril-CoA Desidrogenase/genética Ácido gama-Aminobutírico/efeitos dos fármacos [Mh] Termos MeSH secundário: Erros Inatos do Metabolismo dos Aminoácidos/metabolismo Animais Western Blotting Encefalopatias Metabólicas/metabolismo Cromatografia Líquida de Alta Pressão Epilepsia/metabolismo Antagonistas GABAérgicos/farmacologia Glutamato Descarboxilase Ácido Glutâmico/efeitos dos fármacos Ácido Glutâmico/metabolismo Glutaril-CoA Desidrogenase/metabolismo Camundongos Camundongos Knockout Pentilenotetrazol/farmacologia Sinaptossomos/efeitos dos fármacos Sinaptossomos/metabolismo Ácido gama-Aminobutírico/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (GABA Antagonists); 3KX376GY7L (Glutamic Acid); 56-12-2 (gamma-Aminobutyric Acid); EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase); EC 4.1.1.15 (Glutamate Decarboxylase); WM5Z385K7T (Pentylenetetrazole) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170802 [St] Status: MEDLINE [do] DOI: 10.1111/epi.13862

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[PMID]: 28606041 [Au] Autor: Buckingham SD; Ihara M; Sattelle DB; Matsuda K [Ad] Endereço: Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF. United Kingdom. [Ti] Título: Mechanisms of Action, Resistance and Toxicity of Insecticides Targeting GABA Receptors. [So] Source: Curr Med Chem;24(27):2935-2945, 2017. [Is] ISSN: 1875-533X [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: BACKGROUND: γ-Aminobutyric acid (GABA) receptors play a central role in fast inhibitory neurotransmission in insects. Several classes of insecticides targeting insect GABA-gated chloride channels have been developed. The important resistant to dieldrin GABA receptor subunit (RDL) has been used to investigate insecticide sites of action using radioligands, electrophysiology and site-directed mutagenesis. Although this important subunit readily forms robust functional homomeric receptors when expressed, alternative splicing and RNA A-to-I editing can generate diverse forms of the receptor. METHODS: We have reviewed studies on native and recombinant insect GABA-gated chloride channels, their interactions with ligands acting at orthosteric and allosteric sites and their interactions with insecticides. Since some GABA receptor modulators act on L-glutamate-gated chloride channels, some comparisons are included. RESULTS: The actions on GABA-gated chloride channels of polychlorocycloalkanes, cyclodienes, macrocyclic lactones, phenylpyrazoles, isoxazolines, and metadiamides are described and the mechanisms of action of members of these insecticide classes are addressed. Mutations that lead to resistance are discussed as they can be important in developing field diagnostic tests. Toxicity issues relating to insecticides targeting GABA-gated chloride channels are also addressed. An overview of all major insecticide classes targeting insect GABA-gated chloride channels has enhanced our understanding of these important receptors and their insecticide binding sites. However, the subunit composition of native GABA receptors remains unknown and studies to clarify this are needed. Also, the precise sites of action of the recently introduced isoxazolines and meta-diamides will be of interest to pursue. [Mh] Termos MeSH primário: Inseticidas/metabolismo Receptores de GABA/metabolismo [Mh] Termos MeSH secundário: Animais Resistência a Medicamentos/efeitos dos fármacos Antagonistas GABAérgicos/química Antagonistas GABAérgicos/metabolismo Antagonistas GABAérgicos/toxicidade Seres Humanos Insetos/efeitos dos fármacos Inseticidas/química Inseticidas/toxicidade Oxazóis/química Oxazóis/metabolismo Oxazóis/toxicidade Pirazóis/química Pirazóis/metabolismo Pirazóis/toxicidade Receptores de GABA/química Receptores de GABA/genética Proteínas Recombinantes/biossíntese Proteínas Recombinantes/química [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (GABA Antagonists); 0 (Insecticides); 0 (Oxazoles); 0 (Pyrazoles); 0 (Receptors, GABA); 0 (Recombinant Proteins) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170614 [St] Status: MEDLINE [do] DOI: 10.2174/0929867324666170613075736

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[PMID]: 28428226 [Au] Autor: Nik AM; Pressly B; Singh V; Antrobus S; Hulsizer S; Rogawski MA; Wulff H; Pessah IN [Ad] Endereço: Department of Molecular Biosciences, School of Veterinary Medicine (A.M.N., S.A., S.H., I.N.P.), and Department of Pharmacology (B.P., V.S., M.A.R., H.W.), School of Medicine, University of California Davis, Davis, California; Department of Neurology, School of Medicine, University of California Dav [Ti] Título: Rapid Throughput Analysis of GABA Receptor Subtype Modulators and Blockers Using DiSBAC (3) Membrane Potential Red Dye. [So] Source: Mol Pharmacol;92(1):88-99, 2017 Jul. [Is] ISSN: 1521-0111 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Fluorometric imaging plate reader membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high-throughput drug screening for G-protein-coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABA receptor (GABA R) isoforms (synaptic 1 3 2, extrasynaptic 4 3 , and 3 homopentomers). High-resolution mass spectrometry identified FMP-Red-Dye as 5,5'-(1-propen-1-yl-3-ylidene)bis[1,3-dimethyl-2-thio-barbituric acid]. GABA R-expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane potentials compared with GABA R-null cells. The channel blockers picrotoxin, fipronil, and tetramethylenedisulfotetramine, and the competitive antagonist bicuculline reduced fluorescence near the levels in GABA R-null cells indicating that FMR-Red-Dye, a barbiturate derivative, activates GABA R-mediated outward Cl current in the absence of GABA. GABA caused concentration-dependent increases in fluorescence with rank order of potencies among GABA R isoforms consistent with results from voltage-clamp experiments (EC values for 4 3 , 1 3 2, and homopentamers were 6 ± 1, 40 ± 11, and >18 mM, respectively), whereas GABA R-null cells were unresponsive. Neuroactive steroids (NAS) increased fluorescence of GABA R expressing cells in the absence of GABA and demonstrated positive allosteric modulation in the presence of GABA, whereas benzodiazepines only exhibited positive allosteric modulator (PAM) activity. Of 20 NAS tested, allopregnanolone, (3 ,5 ,20E)-3-hydroxy-13,24-cyclo-18-norcholan-20-ene-21-carbonitrile, eltanolone, 5 -pregnan-3 ,21-diol-20-one, and ganaxolone showed the highest potency. The FMP-Red-Dye-based assay described here provides a sensitive and quantitative method of assessing the activity of GABA R agonists, antagonists, and PAMs on diverse GABA R isoforms. The assay has a wide range of applications, including screening for antiseizure agents and identifying channel blockers of interest to insecticide discovery or biosecurity. [Mh] Termos MeSH primário: Corantes Fluorescentes/metabolismo Antagonistas GABAérgicos/metabolismo Moduladores GABAérgicos/metabolismo Potenciais da Membrana/fisiologia Subunidades Proteicas/metabolismo Receptores de GABA-A/metabolismo [Mh] Termos MeSH secundário: Animais Relação Dose-Resposta a Droga Corantes Fluorescentes/farmacologia Antagonistas GABAérgicos/farmacologia Moduladores GABAérgicos/farmacologia Células HEK293 Seres Humanos Potenciais da Membrana/efeitos dos fármacos Camundongos Subunidades Proteicas/antagonistas & inibidores [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fluorescent Dyes); 0 (GABA Antagonists); 0 (GABA Modulators); 0 (Protein Subunits); 0 (Receptors, GABA-A) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171123 [Lr] Data última revisão: 171123 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170422 [St] Status: MEDLINE [do] DOI: 10.1124/mol.117.108563

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[PMID]: 28413822 [Au] Autor: Wang X; Hong H; Brown DH; Sanchez JT; Wang Y [Ad] Endereço: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306. [Ti] Título: Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear Nucleus Magnocellularis. [So] Source: eNeuro;4(2), 2017 Mar-Apr. [Is] ISSN: 2373-2822 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Topography in the avian cochlear nucleus magnocellularis (NM) is represented as gradually increasing characteristic frequency (CF) along the caudolateral-to-rostromedial axis. In this study, we characterized the organization and cell biophysics of the caudolateral NM (NMc) in chickens ( ). Examination of cellular and dendritic architecture first revealed that NMc contains small neurons and extensive dendritic processes, in contrast to adendritic, large neurons located more rostromedially. Individual dye-filling study further demonstrated that NMc is divided into two subregions, with NMc2 neurons having larger and more complex dendritic fields than NMc1. Axonal tract tracing studies confirmed that NMc1 and NMc2 neurons receive afferent inputs from the auditory nerve and the superior olivary nucleus, similar to the adendritic NM. However, the auditory axons synapse with NMc neurons via small bouton-like terminals, unlike the large end bulb synapses on adendritic NM neurons. Immunocytochemistry demonstrated that most NMc2 neurons express cholecystokinin but not calretinin, distinct from NMc1 and adendritic NM neurons that are cholecystokinin negative and mostly calretinin positive. Finally, whole-cell current clamp recordings revealed that NMc neurons require significantly lower threshold current for action potential generation than adendritic NM neurons. Moreover, in contrast to adendritic NM neurons that generate a single-onset action potential, NMc neurons generate multiple action potentials to suprathreshold sustained depolarization. Taken together, our data indicate that NMc contains multiple neuron types that are structurally, connectively, molecularly, and physiologically different from traditionally defined NM neurons, emphasizing specialized neural properties for processing low-frequency sounds. [Mh] Termos MeSH primário: Vias Auditivas/fisiologia Núcleo Coclear/citologia Neurônios/citologia Neurônios/fisiologia [Mh] Termos MeSH secundário: 2-Amino-5-fosfonovalerato/farmacologia 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia Animais Animais Recém-Nascidos Calbindina 2/metabolismo Embrião de Galinha Galinhas Colecistocinina/metabolismo Núcleo Coclear/embriologia Núcleo Coclear/crescimento & desenvolvimento Dendritos/fisiologia Antagonistas de Aminoácidos Excitatórios/farmacologia Feminino Antagonistas GABAérgicos/farmacologia Imagem Tridimensional Técnicas In Vitro Masculino Potenciais da Membrana/efeitos dos fármacos Potenciais da Membrana/fisiologia Proteínas Associadas aos Microtúbulos/metabolismo Parvalbuminas/metabolismo Técnicas de Patch-Clamp Picrotoxina/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Calbindin 2); 0 (Excitatory Amino Acid Antagonists); 0 (GABA Antagonists); 0 (Microtubule-Associated Proteins); 0 (Parvalbumins); 124-87-8 (Picrotoxin); 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione); 76726-92-6 (2-Amino-5-phosphonovalerate); 9011-97-6 (Cholecystokinin) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 171110 [Lr] Data última revisão: 171110 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170418 [St] Status: MEDLINE

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[PMID]: 28408325 [Au] Autor: Valtcheva S; Paillé V; Dembitskaya Y; Perez S; Gangarossa G; Fino E; Venance L [Ad] Endereço: Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex Paris, France. [Ti] Título: Developmental control of spike-timing-dependent plasticity by tonic GABAergic signaling in striatum. [So] Source: Neuropharmacology;121:261-277, 2017 Jul 15. [Is] ISSN: 1873-7064 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Activity-dependent long-term potentiation (LTP) and depression (LTD) of synaptic strength underlie multiple forms of learning and memory. Spike-timing-dependent plasticity (STDP) has been described as a Hebbian synaptic learning rule that could account for experience-dependent changes in neural networks, but little is known about whether and how STDP evolves during development. We previously showed that GABAergic signaling governs STDP polarity and thus operates as a Hebbian/anti-Hebbian switch in the striatum. Although GABAergic networks are subject to important developmental maturation, it remains unclear whether STDP is developmentally shaped by GABAergic signaling. Here, we investigated whether STDP rules are developmentally regulated at corticostriatal synapses in the dorsolateral striatum. We found that striatal STDP displays unidirectional plasticity (Hebbian tLTD) in young rats (P ) whereas STDP is bidirectional and anti-Hebbian in juvenile (P ) and adult (P ) rats. We also provide evidence that the appearance of tonic (extrasynaptic) GABAergic signaling from the juvenile stage is a crucial factor in shaping STDP rules during development, establishing bidirectional anti-Hebbian STDP in the adult striatum. Thus, developmental maturation of GABAergic signaling tightly drives the polarity of striatal plasticity. [Mh] Termos MeSH primário: Potenciais de Ação/fisiologia Corpo Estriado/citologia Corpo Estriado/crescimento & desenvolvimento Neurônios GABAérgicos/fisiologia Potenciação de Longa Duração/fisiologia Depressão Sináptica de Longo Prazo/fisiologia Transdução de Sinais/fisiologia [Mh] Termos MeSH secundário: 2-Amino-5-fosfonovalerato/farmacologia 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia Fatores Etários Animais Animais Recém-Nascidos Biofísica Estimulação Elétrica Antagonistas de Aminoácidos Excitatórios/farmacologia Antagonistas GABAérgicos/farmacologia Técnicas In Vitro Técnicas de Patch-Clamp Picrotoxina/farmacologia Ratos Ácido gama-Aminobutírico/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Excitatory Amino Acid Antagonists); 0 (GABA Antagonists); 124-87-8 (Picrotoxin); 56-12-2 (gamma-Aminobutyric Acid); 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione); 76726-92-6 (2-Amino-5-phosphonovalerate) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170906 [Lr] Data última revisão: 170906 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170415 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28361168 [Au] Autor: Bogatyrev S; Yakimova KS; Tzschentke B [Ad] Endereço: Faculty of Life Science, Institute of Biology, Humboldt-Universität zu Berlin, 10115, Berlin, Germany. [Ti] Título: Influence of leptin and GABA -receptor agonist and antagonist on neurons of the hypothalamic infundibular nucleus in the chicken. [So] Source: J Comp Physiol A Neuroethol Sens Neural Behav Physiol;203(4):291-299, 2017 Apr. [Is] ISSN: 1432-1351 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: In birds and mammals, the neuroendocrine regulation of energy balance is conserved in many aspects. Despite significant similarities between the two groups, differences in the regulatory mechanisms were detected. The present study was performed to carry out investigations of the influence of human leptin and GABA -receptor agonist and antagonist on the firing rate of neurons of the Nucleus infundibuli hypothalami in brain slices from juvenile chickens. For the first time, we demonstrated a clear, dose-related change in the firing rate of hypothalamic neurons in juvenile chickens after the acute application of recombinant human leptin (1, 10, and 100 nM). All investigated neurons increased their subsequent firing rate. Application of GABA -receptor agonist baclofen (1 µM) blocked, while antagonist CGP 35348 (10 µM) increased the spontaneous neuronal activity. Simultaneous application of baclofen and leptin reduced the effect observed from single leptin application. This was not found after simultaneously application of leptin and CGP. Altogether, our results indicate that in bird brain slices, and exemplarily in those of the chicken, hypothalamic neurons show mammalian-like responsiveness after acute leptin and GABA application. GABA -mechanisms involved in GABA release play a likely important role in the leptin-mediated effects on NI neurons via functional leptin receptors. [Mh] Termos MeSH primário: Núcleo Arqueado do Hipotálamo/citologia Antagonistas GABAérgicos/farmacologia Agonistas dos Receptores de GABA-B/farmacologia Leptina/farmacologia Neurônios/efeitos dos fármacos [Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos Animais Baclofeno/farmacologia Galinhas Relação Dose-Resposta a Droga Feminino Técnicas In Vitro Masculino Compostos Organofosforados/farmacologia Técnicas de Patch-Clamp Ácido gama-Aminobutírico/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (GABA Antagonists); 0 (GABA-B Receptor Agonists); 0 (Leptin); 0 (Organophosphorus Compounds); 56-12-2 (gamma-Aminobutyric Acid); 87TI61875H (CGP 35348); H789N3FKE8 (Baclofen) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171014 [Lr] Data última revisão: 171014 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170401 [St] Status: MEDLINE [do] DOI: 10.1007/s00359-017-1168-6

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[PMID]: 28242439 [Au] Autor: Boddum K; Hougaard C; Xiao-Ying Lin J; von Schoubye NL; Jensen HS; Grunnet M; Jespersen T [Ad] Endereço: Cardiac Physiology Laboratory, University of Copenhagen, Faculty of Health Sciences, Department of Biomedical Sciences, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark. Electronic address: kimboddum@sund.ku.dk. [Ti] Título: K 3.1/K 3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons. [So] Source: Neuropharmacology;118:102-112, 2017 May 15. [Is] ISSN: 1873-7064 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Due to their fast kinetic properties, K 3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of K 3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on K 3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on K 3.1 and to a minor extent on K 3.2 channels. RE01 had no effect on the K 3.3 and K 3.4 channels, whereas EX15 had an inhibitory impact on the K 3.4 mediated current. Voltage-clamp experiments in monoclonal hK 3.1b/HEK293 cells (34 °C) revealed that the two compounds indeed induced larger currents and faster activation kinetics. They also decrease the speed of deactivation and shifted the voltage dependence of activation, to a more negative activation threshold. Application of action potential clamping and repetitive stimulation protocols of hK 3.1b expressing HEK293 cells revealed that EX15 and RE01 significantly increased peak amplitude, half width and decay time of K 3.1 mediated currents, even during high-frequency action potential clamping (250 Hz). In rat hippocampal slices, EX15 and RE01 increased neuronal excitability in fast-spiking interneurons in dentate gyrus. Action potential frequency was prominently increased at minor depolarizing steps, whereas more marginal effects of EX15 and RE01 were observed after stronger depolarizations. In conclusion, our results suggest that EX15 and RE01 positive modulation of K 3.1 and K 3.2 currents facilitate increased firing frequency in fast-spiking GABAergic interneurons. [Mh] Termos MeSH primário: Potenciais de Ação/fisiologia Fenômenos Biofísicos/fisiologia Neurônios GABAérgicos/fisiologia Hidantoínas/farmacologia Piridinas/farmacologia Canais de Potássio Shaw/metabolismo [Mh] Termos MeSH secundário: 2-Amino-5-fosfonovalerato/farmacologia Potenciais de Ação/efeitos dos fármacos Animais Fenômenos Biofísicos/efeitos dos fármacos Encéfalo/citologia Antagonistas de Aminoácidos Excitatórios/farmacologia Antagonistas GABAérgicos/farmacologia Neurônios GABAérgicos/efeitos dos fármacos Células HEK293 Seres Humanos Cinética Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Transgênicos Oócitos Piridazinas/farmacologia Quinoxalinas/farmacologia Ratos Ratos Sprague-Dawley Proteínas Repressoras/farmacologia Proteínas de Saccharomyces cerevisiae/farmacologia Canais de Potássio Shaw/genética Xenopus laevis [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (EX15 hydantoin compound); 0 (Excitatory Amino Acid Antagonists); 0 (GABA Antagonists); 0 (Hydantoins); 0 (Pyridazines); 0 (Pyridines); 0 (Quinoxalines); 0 (ROX1 protein, S cerevisiae); 0 (Repressor Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (Shaw Potassium Channels); 62T278S1MX (FG 9041); 76726-92-6 (2-Amino-5-phosphonovalerate); 99460MG420 (gabazine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170906 [Lr] Data última revisão: 170906 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170301 [St] Status: MEDLINE

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