Developmental regulation of voltage-gated K+ channel and GABAA receptor expression in Bergmann glial cells

Müller, Thomas; Fritschy, Jean‐Marc; Grosche, Jens; Pratt, GD; Möhler, Hans; Kettenmann, Helmut

doi:10.1523/jneurosci.14-05-02503.1994

Cited by 109 publications

(104 citation statements)

References 18 publications

(23 reference statements)

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“…In this mouse line, delivery of the blue light produced a constant inward current in PCs, which was rapidly terminated with the yellow light pulse. We assumed that the cause of the additional current in BGs is the high conductance of BGs to K + making them sensitive to changes in extracellular K + concentrations (22). As expected, 5 mM Ba 2+ and 5 mM 4-aminopyridine (4-AP), K + channel blockers, inhibited a large fraction of the slow component, whereas the fast component remained intact (Fig.…”

Section: Resultsmentioning

confidence: 61%

Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Sasaki

Beppu

Tanaka

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

144

172

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Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glialto-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function.cerebellum | Bergmann glia | gliotransmitter | plasticity | c-fos

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Section: Resultsmentioning

confidence: 61%

Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Sasaki

Beppu

Tanaka

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

144

172

View full text Add to dashboard Cite

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“…Reports of potential interactions of GABA and bicuculline methiodide (GABA A antagonist) with voltage-gated K ϩ channels (11,13,24) raise the possibility of non-specific GABA A agonist effects at the maxi-K channel contributing to the prorelaxant effects we observed. To illustrate that GABA A channel augmentation of isoproterenol-mediated relaxation occurs independent of relaxation achieved due to opening of the maxi K ϩ channel, we performed experiments under conditions of iberiotoxin blockade of the maxi K ϩ channel.…”

Section: Discussionmentioning

confidence: 83%

Activation of endogenous GABA_A channels on airway smooth muscle potentiates isoproterenol-mediated relaxation

Gallos¹,

Gleason²,

Zhang³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Emala CW. Activation of endogenous GABAA channels on airway smooth muscle potentiates isoproterenol-mediated relaxation. Am J Physiol Lung Cell Mol Physiol 295: L1040 -L1047, 2008. First published September 12, 2008 doi:10.1152/ajplung.90330.2008.-Reactive airway disease predisposes patients to episodes of acute smooth muscle mediated bronchoconstriction. We have for the first time recently demonstrated the expression and function of endogenous ionotropic GABAA channels on airway smooth muscle cells. We questioned whether endogenous GABAA channels on airway smooth muscle could augment ␤-agonist-mediated relaxation. Guinea pig tracheal rings or human bronchial airway smooth muscles were equilibrated in organ baths with continuous digital tension recordings. After pretreatment with or without the selective GABAA antagonist gabazine (100 M), airway muscle was contracted with acetylcholine or ␤-ala neurokinin A, followed by relaxation induced by cumulatively increasing concentrations of isoproterenol (1 nM to 1 M) in the absence or presence of the selective GABAA agonist muscimol (10 -100 M). In separate experiments, guinea pig tracheal rings were pretreated with the large conductance KCa channel blocker iberiotoxin (100 nM) after an EC50 contraction with acetylcholine but before cumulatively increasing concentrations of isoproterenol (1 nM to 1 uM) in the absence or presence of muscimol (100 uM). GABAA activation potentiated the relaxant effects of isoproterenol after an acetylcholine or tachykinin-induced contraction in guinea pig tracheal rings or an acetylcholine-induced contraction in human endobronchial smooth muscle. This muscimol-induced potentiation of relaxation was abolished by gabazine pretreatment but persisted after blockade of the maxi KCa channel. Selective activation of endogenous GABAA receptors significantly augments ␤-agonist-mediated relaxation of guinea pig and human airway smooth muscle, which may have important therapeutic implications for patients in severe bronchospasm. guinea pig; organ bath; gabazine; muscimol ASTHMA IS A CHRONIC inflammatory disease of the airways the prevalence of which both in the United States and throughout much of the world has taken on pandemic proportions (4). Standard treatment for asthma centers on pharmacological attenuation of hyperresponsiveness either by modulation of inflammatory mediators or by promoting airway smooth muscle (ASM) relaxation (e.g., ␤ 2 -adrenoceptor agonists). Although research over the past three decades has made great strides in elucidating many of the underlying mechanisms involved in this disease, few novel additions to the pharmacological armamentarium have occurred in the treatment of reactive airway disease.␤ 2 -Adrenoceptor agonists retain a prominent role in the clinical treatment of airway hyperresponsiveness, and the mechanisms by which ␤ 2 -adrenoceptor agonists relax ASM include both cAMP-dependent and cAMP-independent pathways. Additionally, regulation of ␤ 2 -adrenoceptor activity either through desensitization or downregu...

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“…Despite this plethora of subunits, the majority of cell types express a limited repertoire of GABA A receptor subtypes ( Figure 1). For example, PC express exclusively a1bxc2-GABA A receptors; stellate/basket cells, a1bxc2 and a3bxc2; Golgi cells a3bxc2; Bergmann glia, a2/bx/c1 (8)(9)(10)(11)(12)(13)(14). The notable exception comes from granule cells, which express multiple receptor subtypes, despite receiving GABAergic input only from Golgi cells (15).…”

Section: Organization Of Gaba a Receptors In The Cerebellar Cortexmentioning

confidence: 99%

“…A distinct population of 'extrasynaptic', diazepam-insensitive GABA A receptors, with a probably unique subunit composition in brain (a2bxc1), is found in Bergman glia cells (10,11,14). These receptors are most abundant during early postnatal maturation and modulate K + conductances that are transiently expressed by immature Bergmann glia.…”

Section: Organization Of Gaba a Receptors In The Cerebellar Cortexmentioning

confidence: 99%

“…The subunit composition and pharmacological profile of GABA A receptor in granule cells are developmentally regulated and these changes are activitydependent (54)(55)(56)(57). A transient expression of the a2 and a3 subunit occurs at early postnatal stages (58)(59)(60), whereas the a6 and d subunit, which are expressed selectively in granule cells (61), is delayed (11,55,60) and parallels the formation of functional GABAergic synapses from Golgi cells (62)(63)(64)(65). This maturation pattern contrasts with that of PC, which express a prominent a1 subunit immunoreactivity at birth, before having formed a monolayer and being innervated by basket and stellate cells (66,67).…”

Section: Organization Of Gaba a Receptors In The Cerebellar Cortexmentioning

confidence: 99%

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Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

Fritschy

Panzanelli

2006

Cerebellum

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GABA A receptors form heteromeric GABA-gated chloride channels assembled from a large family of subunit genes. In cerebellum, distinct GABA A receptor subtypes, differing in subunit composition, are segregated between cell types and synaptic circuits. The cerebellum therefore represents a useful system to investigate the significance of GABA A receptor heterogeneity. For instance, studies of mice carrying targeted deletion of major GABA A receptor subunit genes revealed the role of a subunit variants for receptor assembly, synaptic targeting, and functional properties. In addition, these studies unraveled mandatory association between certain subunits and demonstrated distinct pharmacology of receptors mediating phasic and tonic inhibition. Although some of these mutants have a profound loss of GABA A receptors, they exhibit only minor impairment of motor function, suggesting activation of compensatory mechanisms to preserve inhibitory networks in the cerebellum. These adaptations include an altered balance between phasic and tonic inhibition, activation of voltageindependent K + conductances, and upregulation of GABA A receptors in interneurons that are not affected directly by the mutation. Deletion of the a1 subunit gene leads to complete loss of GABA A receptors in Purkinje cells. A striking alteration occurs in these mice, whereby presynaptic GABAergic terminals are preserved in the molecular layer but make heterologous synapses with spines, characterized by a glutamatergic-like postsynaptic density. During development of a1 0/0 mice, GABAergic synapses are initially formed but are replaced upon spine maturation. These findings suggest that functional GABA A receptors are required for long-term maintenance of GABAergic synapses in Purkinje cells.

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Developmental regulation of voltage-gated K+ channel and GABAA receptor expression in Bergmann glial cells

Cited by 109 publications

References 18 publications

Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Activation of endogenous GABA_A channels on airway smooth muscle potentiates isoproterenol-mediated relaxation

Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

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