Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling

Veruki, Margaret Lin; Mørkve, Svein Harald; Hartveit, Espen

doi:10.1038/nn1793

Cited by 159 publications

(180 citation statements)

References 49 publications

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“…This suggests that GluNRs could be involved in modulatory regulation of the electrical synapses and that extrasynaptic receptors could be activated by spillover of glutamate escaping from the synaptic cleft after release from bipolar cells. Veruki et al (2006) found evidence for spillover of glutamate between neighboring rod bipolar cells and that ambient and transiently released glutamate can activate a glutamate transporter on rod bipolar axon terminals (see also Wersinger et al, 2006). This could imply that ambient levels of glutamate might be sufficient to activate GluNRs on AII amacrines and contribute to regulating the junctional conductance of their electrical synapses.…”

Section: Nmda Receptors In Aii Amacrine Cellsmentioning

confidence: 95%

Electrical synapses between AII amacrine cells in the retina: Function and modulation

Hartveit

Veruki

2012

Brain Research

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Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca 2+ dynamics.

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Section: Nmda Receptors In Aii Amacrine Cellsmentioning

confidence: 95%

Electrical synapses between AII amacrine cells in the retina: Function and modulation

Hartveit

Veruki

2012

Brain Research

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“…Second, voltagedependent mechanisms could induce gain control in bipolar cells (Mao et al, 1998). Finally, a gain-control mechanism could act at the point of bipolar cell synaptic release (Palmer et al, 2003a,b;Singer and Diamond, 2006;Veruki et al, 2006). Such a synaptic mechanism would explain why one study found much stronger gain control in ganglion cell membrane potential than in bipolar cells, recorded in the same preparation (Baccus and Meister, 2002).…”

Section: Bipolar Cell Roles In Contrast Gain Control and Slow Contrasmentioning

confidence: 99%

Cellular Basis for Contrast Gain Control over the Receptive Field Center of Mammalian Retinal Ganglion Cells

Beaudoin¹,

Borghuis²,

Demb³

2007

J. Neurosci.

114

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Retinal ganglion cells fire spikes to an appropriate contrast presented over their receptive field center. These center responses undergo dynamic changes in sensitivity depending on the ongoing level of contrast, a process known as "contrast gain control." Extracellular recordings suggested that gain control is driven by a single wide-field mechanism, extending across the center and beyond, that depends on inhibitory interneurons: amacrine cells. However, recordings in salamander suggested that the excitatory bipolar cells, which drive the center, may themselves show gain control independently of amacrine cell mechanisms. Here, we tested in mammalian ganglion cells whether amacrine cells are critical for gain control over the receptive field center. We made extracellular and whole-cell recordings of guinea pig Y-type cells in vitro and quantified the gain change between contrasts using a linear-nonlinear analysis. For spikes, tripling contrast reduced gain by ϳ40%. With spikes blocked, ganglion cells showed similar levels of gain control in membrane currents and voltages and under conditions of low and high calcium buffering: tripling contrast reduced gain by ϳ20 -25%. Gain control persisted under voltage-clamp conditions that minimize inhibitory conductances and pharmacological conditions that block inhibitory neurotransmitter receptors. Gain control depended on adequate stimulation, not of ganglion cells but of presynaptic bipolar cells. Furthermore, horizontal cell measurements showed a lack of gain control in photoreceptor synaptic release. Thus, the mechanism for gain control over the ganglion cell receptive field center, as measured in the subthreshold response, originates in the presynaptic bipolar cells and does not require amacrine cell signaling.

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“…Different EAAT isoforms differ in the relative contribution of anion currents to the total transporter-mediated current (5)(6)(7)(8). These differences have been interpreted as an indication that some EAATs play a physiological role as glutamate transporters (9,10) and others as glutamate-gated anion channels involved in the regulation of cellular excitability (2,11,12).…”

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confidence: 99%

Hetero-oligomerization of Neuronal Glutamate Transporters

Nothmann

Leinenweber

Torres-Salazar

et al. 2011

Journal of Biological Chemistry

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Excitatory amino acid transporters (EAATs) mediate the uptake of glutamate into neuronal and glial cells of the mammalian central nervous system. Two transporters expressed primarily in glia, EAAT1 and EAAT2, are crucial for glutamate homeostasis in the adult mammalian brain. Three neuronal transporters (EAAT3, EAAT4, and EAAT5) appear to have additional functions in regulating and processing cellular excitability. EAATs are assembled as trimers, and the existence of multiple isoforms raises the question of whether certain isoforms can form hetero-oligomers. Co-expression and pulldown experiments of various glutamate transporters showed that EAAT3 and EAAT4, but neither EAAT1 and EAAT2, nor EAAT2 and EAAT3 are capable of co-assembling into heterotrimers. To study the functional consequences of hetero-oligomerization, we co-expressed EAAT3 and the serine-dependent mutant R501C EAAT4 in HEK293 cells and Xenopus laevis oocytes and studied glutamate/serine transport and anion conduction using electrophysiological methods. Individual subunits transport glutamate independently of each other. Apparent substrate affinities are not affected by hetero-oligomerization. However, polarized localization in Madin-Darby canine kidney cells was different for homo-and hetero-oligomers. EAAT3 inserts exclusively into apical membranes of Madin-Darby canine kidney cells when expressed alone. Co-expression with EAAT4 results in additional appearance of basolateral EAAT3. Our results demonstrate the existence of heterotrimeric glutamate transporters and provide novel information about the physiological impact of EAAT oligomerization.

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Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling

Cited by 159 publications

References 49 publications

Electrical synapses between AII amacrine cells in the retina: Function and modulation

Electrical synapses between AII amacrine cells in the retina: Function and modulation

Cellular Basis for Contrast Gain Control over the Receptive Field Center of Mammalian Retinal Ganglion Cells

Hetero-oligomerization of Neuronal Glutamate Transporters

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