Compartment-Dependent Colocalization of Kir3.2-Containing K<sup>+</sup>Channels and GABA<sub>B</sub>Receptors in Hippocampal Pyramidal Cells

Kulik, Ákos; Vida, Imre; Fukazawa, Yugo; Guetg, Nicole; Kasugai, Yu; Marker, Cheryl L.; Rigato, Franck; Bettler, Bernhard; Wickman, Kevin; Frotscher, Michael; Shigemoto, Ryuichi

doi:10.1523/jneurosci.4178-05.2006

Cited by 131 publications

(165 citation statements)

References 75 publications

(91 reference statements)

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“…Its sensitivity to both CGP55845 and tertiapin-Q suggests instead that GABA released along the axon of the recorded GC activates GABAB autoreceptors coupled to GIRK channels. Although coupling of presynaptic GABAB receptors to transmitter release may involve modulation of Ca 2ϩ rather than K ϩ channels (Lüscher et al, 1997), several recent reports reveal the presence of presynaptic GIRK channels (Kulik et al, 2006;Ladera et al, 2008;Michaeli and Yaka, 2010) that may be coupled to GABAB receptors (Kulik et al, 2006;Lujan et al, 2009). The mechanisms by which activation of GIRK channels may induce prolonged (Ͼ30 s) changes in axonal excitability remain to be fully characterized but may involve hyperpolarization-induced, deinactivation of potassium currents.…”

Section: Discussionmentioning

confidence: 99%

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

Cabezas

Irinopoulou²,

Gauvain³

et al. 2012

J. Neurosci.

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Dentate gyrus granule cells have been suggested to corelease GABA and glutamate both in juvenile animals and under pathological conditions in adults. Although mossy fiber terminals (MFTs) are known to express glutamic acid decarboxylase (GAD) in early postnatal development, the functional role of GABA synthesis in MFTs remains controversial, and direct evidence for synaptic GABA release from MFTs is missing. Here, using GAD67-GFP transgenic mice, we show that GAD67 is expressed only in a population of immature granule cells in juvenile animals. We demonstrate that GABA can be released from these cells and modulate mossy fiber excitability through activation of GABAB autoreceptors. However, unitary postsynaptic currents generated by individual, GAD67-expressing granule cells are purely glutamatergic in all postsynaptic cell types tested. Thus GAD67 expression does not endow dentate gyrus granule cells with a full GABAergic phenotype and GABA primarily instructs the pre-rather than the postsynaptic element.

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Section: Discussionmentioning

confidence: 99%

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

Cabezas

Irinopoulou²,

Gauvain³

et al. 2012

J. Neurosci.

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“…Consistent with this, we found that GABA B receptors undergo endocytosis in dendritic spines and shafts within minutes of NMDA receptor activation. Notably, endocytosis prevents GABA B receptors from activating effector K + channels that cluster with GABA B receptors in spines (12).…”

Section: Discussionmentioning

confidence: 99%

“…Well-known effectors of dendritic GABA B receptors are the Kir3-type K + channels, which cluster with GABA B receptors in spines (12). We used whole-cell patch-clamp recording to address whether NMDA-treatment reduces baclofen-induced K + currents due to GABA B receptor internalization.…”

Section: Nmda Receptorsmentioning

confidence: 99%

“…Genetically modified mice revealed that the two receptors convey nonredundant synaptic functions at glutamatergic synapses, owing to their differing distribution to axonal and dendritic compartments (3,9). Selectively GABA B(1a,2) receptors control the release of glutamate, whereas predominantly GABA B(1b,2) receptors activate postsynaptic Kir3 channels in dendritic spines (10)(11)(12). Activation of GABA B receptors on spines inhibits NMDA receptors through hyperpolarization and the PKA pathway, which enhances Mg 2+ block (13,14) and reduces Ca 2+ permeability (15) of NMDA receptors.…”

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confidence: 99%

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NMDA receptor-dependent GABA _B receptor internalization via CaMKII phosphorylation of serine 867 in GABA _B1

Guetg

Aziz

Holbro

et al. 2010

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

130

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GABA B receptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GABA B receptors are abundant on dendritic spines, where they dampen postsynaptic excitability and inhibit Ca 2+ influx through NMDA receptors when activated by spillover of GABA from neighboring GABAergic terminals. Here, we show that an excitatory signaling cascade enables spines to counteract this GABA B -mediated inhibition. We found that NMDA application to cultured hippocampal neurons promotes dynamindependent endocytosis of GABA B receptors. NMDA-dependent internalization of GABA B receptors requires activation of Ca 2+ /Calmodulindependent protein kinase II (CaMKII), which associates with GABA B receptors in vivo and phosphorylates serine 867 (S867) in the intracellular C terminus of the GABA B1 subunit. Blockade of either CaMKII or phosphorylation of S867 renders GABA B receptors refractory to NMDA-mediated internalization. Time-lapse two-photon imaging of organotypic hippocampal slices reveals that activation of NMDA receptors removes GABA B receptors within minutes from the surface of dendritic spines and shafts. NMDA-dependent S867 phosphorylation and internalization is predominantly detectable with the GABA B1b subunit isoform, which is the isoform that clusters with inhibitory effector K + channels in the spines. Consistent with this, NMDA receptor activation in neurons impairs the ability of GABA B receptors to activate K + channels. Thus, our data support that NMDA receptor activity endocytoses postsynaptic GABA B receptors through CaMKIImediated phosphorylation of S867. This provides a means to spare NMDA receptors at individual glutamatergic synapses from reciprocal inhibition through GABA B receptors.γ-aminobutyric acid | spines | trafficking | synaptic plasticity | GABAB

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“…By performing SDS-digested freeze-fracture replica immunolabeling (Hagiwara et al, 2005;Kulik et al, 2006), we found ␤1-integrin in presynaptic compartments of CA1 synapses. Anti-SNAP25 labeling was used to identify presynaptic compartments (Fig.…”

Section: Presynaptic Localization Of ␤1-integrin In Ca1 Synapsesmentioning

confidence: 94%

Role for Reelin in Neurotransmitter Release

Hellwig¹,

Hack²,

Kowalski³

et al. 2011

J. Neurosci.

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The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic analysis of the number of presynaptic boutons in the stratum radiatum of hippocampal region CA1 did not reveal differences between wild-type animals and Reelin-deficient reeler mutant mice. However, additional detailed analysis showed that the number of presynaptic vesicles was significantly increased in CA1 synapses of reeler mutants. To test the hypothesis that vesicle fusion is altered in reeler, we studied proteins known to control transmitter release. SNAP25, a protein of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was found to be significantly reduced in reeler mutants, whereas other SNARE complex proteins remained unaltered. Addition of recombinant Reelin to organotypic slice cultures of reeler hippocampi substantially rescued not only SNAP25 protein expression levels but also the number of vesicles per bouton area indicating a role for Reelin in presynaptic functions. Next, we analyzed paired-pulse facilitation, a presynaptic mechanism associated with transmitter release, and observed a significant decrease at CA1 synapses of reeler mutants when compared with wild-type animals. Together, these novel findings suggest a role for Reelin in modulating presynaptic release mechanisms.

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Compartment-Dependent Colocalization of Kir3.2-Containing K⁺Channels and GABA_BReceptors in Hippocampal Pyramidal Cells

Cited by 131 publications

References 75 publications

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

NMDA receptor-dependent GABA _B receptor internalization via CaMKII phosphorylation of serine 867 in GABA _B1

Role for Reelin in Neurotransmitter Release

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Compartment-Dependent Colocalization of Kir3.2-Containing K+Channels and GABABReceptors in Hippocampal Pyramidal Cells

Cited by 131 publications

References 75 publications

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

NMDA receptor-dependent GABA B receptor internalization via CaMKII phosphorylation of serine 867 in GABA B1

Role for Reelin in Neurotransmitter Release

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Product

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Compartment-Dependent Colocalization of Kir3.2-Containing K⁺Channels and GABA_BReceptors in Hippocampal Pyramidal Cells

NMDA receptor-dependent GABA _B receptor internalization via CaMKII phosphorylation of serine 867 in GABA _B1